Consanguinity and epilepsy in Oran, Algeria: A case-control study.

PubMed

Chentouf, Amina; Talhi, Randa; Dahdouh, Aicha; Benbihi, Latifa; Benilha, Soumia; Oubaiche, Mohand Laid; Chaouch, Malika

2015-03-01

The goal of this case-control study was to identify the significance of consanguinity and other risk factors for epilepsy in Oran, Algeria. Unrelated epileptic patients upwards of 16 years, who attended the Neurology Department between October 2013 and March 2014 were included in the study. Controls, matched for age and sex, were selected among non-epileptic patients attending the same department during the same period. The risk factors evaluated were: consanguinity, family history of epilepsy, perinatal complications, infection of the central nervous system, mental retardation, neurological impairment, history of febrile seizures, severe head trauma, cerebrovascular diseases, and addiction. 101 cases and 202 controls participated in the study. Multivariate logistic regression identified five factors significantly associated with epilepsy: first-degree of consanguinity (odds ratio (OR)=2.15), history of epilepsy in first-degree relatives (OR=4.03), antecedent of febrile seizures (OR=5.38), severe head injury (OR=2.94) and mental retardation (OR=9.32). Consanguinity, family history of epilepsy, history of febrile seizures, severe head trauma and mental retardation are risk factors for epilepsy. The implementation of a strategy for prevention and awareness of the impact of consanguineous marriages as well as genetic counseling for couples with a family history of epilepsy are needed. Copyright © 2015 Elsevier B.V. All rights reserved.

Changing profile of couples seeking genetic counseling for consanguinity in Australia.

PubMed

Port, Katrina E; Mountain, Helen; Nelson, John; Bittles, Alan H

2005-01-15

Consanguineous marriage is rare in most Western countries and, for example, in the USA it may be subject to regulation by both civil legislation and religious prescription. This is not the case in many regions of Asia and Africa where marriage within the family is strongly favored. Since the 1970s there has been widespread migration to North America, Western Europe, and Australasia from communities which encourage consanguineous marriage. To assess the effect of this trend on a genetic counseling program, the records of 302 couples referred to Genetic Services of Western Australia for consanguinity counseling were abstracted for the period 1975-2001. Overall, a family history of genetic disease or a previously affected child was reported in 28.8% of cases. Premarital or prepregnancy counseling on grounds of consanguinity was sought by 41.0% of couples, and a further 18.2% of consanguineous couples had been referred because of a consanguineous pregnancy. In 7.6% of cases a relationship closer than first cousin was involved. Through time there was a significant increase in the numbers of consanguineous consultants, and their patterns of religious affiliation and ethnic origin widened markedly. Although effectively excluded from entry to Australia prior to 1975, couples of Asian origin accounted for 25.5% of all consanguineous consultants. With ongoing migration, changes in the ethnic profiles and the specific counseling requirements of consanguineous couples can be expected to continue and probably accelerate.

Increased Probability of Co-Occurrence of Two Rare Diseases in Consanguineous Families and Resolution of a Complex Phenotype by Next Generation Sequencing

PubMed Central

Lal, Dennis; Neubauer, Bernd A.; Toliat, Mohammad R.; Altmüller, Janine; Thiele, Holger; Nürnberg, Peter; Kamrath, Clemens; Schänzer, Anne; Sander, Thomas; Hahn, Andreas; Nothnagel, Michael

2016-01-01

Massively parallel sequencing of whole genomes and exomes has facilitated a direct assessment of causative genetic variation, now enabling the identification of genetic factors involved in rare diseases (RD) with Mendelian inheritance patterns on an almost routine basis. Here, we describe the illustrative case of a single consanguineous family where this strategy suffered from the difficulty to distinguish between two etiologically distinct disorders, namely the co-occurrence of hereditary hypophosphatemic rickets (HRR) and congenital myopathies (CM), by their phenotypic manifestation alone. We used parametric linkage analysis, homozygosity mapping and whole exome-sequencing to identify mutations underlying HRR and CM. We also present an approximate approach for assessing the probability of co-occurrence of two unlinked recessive RD in a single family as a function of the degree of consanguinity and the frequency of the disease-causing alleles. Linkage analysis and homozygosity mapping yielded elusive results when assuming a single RD, but whole-exome sequencing helped to identify two mutations in two genes, namely SLC34A3 and SEPN1, that segregated independently in this family and that have previously been linked to two etiologically different diseases. We assess the increase in chance co-occurrence of rare diseases due to consanguinity, i.e. under circumstances that generally favor linkage mapping of recessive disease, and show that this probability can increase by several orders of magnitudes. We conclude that such potential co-occurrence represents an underestimated risk when analyzing rare or undefined diseases in consanguineous families and should be given more consideration in the clinical and genetic evaluation. PMID:26789268

Sequence variants in four genes underlying Bardet-Biedl syndrome in consanguineous families

PubMed Central

Ullah, Asmat; Umair, Muhammad; Yousaf, Maryam; Khan, Sher Alam; Nazim-ud-din, Muhammad; Shah, Khadim; Ahmad, Farooq; Azeem, Zahid; Ali, Ghazanfar; Alhaddad, Bader; Rafique, Afzal; Jan, Abid; Haack, Tobias B.; Strom, Tim M.; Meitinger, Thomas; Ghous, Tahseen

2017-01-01

Purpose To investigate the molecular basis of Bardet-Biedl syndrome (BBS) in five consanguineous families of Pakistani origin. Methods Linkage in two families (A and B) was established to BBS7 on chromosome 4q27, in family C to BBS8 on chromosome 14q32.1, and in family D to BBS10 on chromosome 12q21.2. Family E was investigated directly with exome sequence analysis. Results Sanger sequencing revealed two novel mutations and three previously reported mutations in the BBS genes. These mutations include two deletions (c.580_582delGCA, c.1592_1597delTTCCAG) in the BBS7 gene, a missense mutation (p.Gln449His) in the BBS8 gene, a frameshift mutation (c.271_272insT) in the BBS10 gene, and a nonsense mutation (p.Ser40*) in the MKKS (BBS6) gene. Conclusions Two novel mutations and three previously reported variants, identified in the present study, further extend the body of evidence implicating BBS6, BBS7, BBS8, and BBS10 in causing BBS. PMID:28761321

Lack of KIF21A mutations in congenital fibrosis of the extraocular muscles type I patients from consanguineous Saudi Arabian families

PubMed Central

Shinwari, Jameela; Omar, Aisha; Al-Sharif, Latifa; Khalil, Dania S.; Alanazi, Mohammed; Al-Amri, Abdullah; Al Tassan, Nada

2011-01-01

Purpose Congenital fibrosis of the extraocular muscles type I (CFEOM1), the most common CFEOM worldwide, is characterized by bilateral ptotic hypotropia, an inability to supraduct above the horizontal midline, horizontal strabismus (typically exotropia), and ophthalmoplegia with abnormal synkinesis. This distinct non-syndromic phenotype is considered autosomal dominant and is virtually always from heterozygous missense mutations in kinesin family member 21A (KIF21A). However, there are occasional KIF21A-negative cases, opening the possibility for a recessive cause. The objective of this study is to explore this possibility by assessing CFEOM1 patients exclusively from consanguineous families, who are the most likely to have recessive cause for their phenotype if a recessive cause exists. Methods Ophthalmic examination and candidate gene direct sequencing (KIF21A, paired-like homeobox 2A [PHOX2A], tubulin beta-3 [TUBB3]) of CFEOM1 patients from consanguineous families referred for counseling from 2005 to 2010. Results All 5 probands had classic CFEOM1 as defined above. Three had siblings with CFEOM. None of the probands had mutations in KIF21A, PHOX2A, or TUBB3. Conclusions The lack of KIF21A mutations in CFEOM1 patients exclusively from consanguineous families, most of whom had siblings with CFEOM, is strong evidence for a recessive form of CFEOM1. Further studies of such families will hopefully uncover the specific locus(loci). PMID:21264235

Congenital abnormalities in newborns of consanguineous and nonconsanguineous parents.

PubMed

Naderi, S

1979-02-01

The aim of this study was to determine the types, patterns, and frequencies of congenital anomalies among newborns of both consanguineous and nonconsanguineous parents in southern Iran. From 9526 consecutive pregnancies observed, 9623 newborns resulted (9431 singleton and 95 sets of multiple gestation). There were 7261 newborns from nonconsanguineous parents and 2362 (24.5%) babies from consanguineous marriages. Of the total pregnancies, 1.54% resulted in malformed children (1.53% of singleton and 2.1% of multiple gestations). The incidence of congenital abnormalities in newborns of nonconsanguineous parents was 1.66% as compared to 4.02% for newborns of the consanguineous group. Major and multiple malformations were found to be slightly more common in the consanguinous group. Prematurity, prenatal mortality rate, and congenital abnormalities were more common in the consanguineous group. Probably the closer the familial relationship of the parents, the greater the chances of congenital abnormalities.

In silico analysis of a disease-causing mutation in PCDH15 gene in a consanguineous Pakistani family with Usher phenotype.

PubMed

Saleha, Shamim; Ajmal, Muhammad; Jamil, Muhammad; Nasir, Muhammad; Hameed, Abdul

2016-01-01

To map Usher phenotype in a consanguineous Pakistani family and identify disease-associated mutation in a causative gene to establish phenotype-genotype correlation. A consanguineous Pakistani family in which Usher phenotype was segregating as an autosomal recessive trait was ascertained. On the basis of results of clinical investigations of affected members of this family disease was diagnosed as Usher syndrome (USH). To identify the locus responsible for the Usher phenotype in this family, genomic DNA from blood sample of each individual was genotyped using microsatellite Short Tandem Repeat (STR) markers for the known Usher syndrome loci. Then direct sequencing was performed to find out disease associated mutations in the candidate gene. By genetic linkage analysis, the USH phenotype of this family was mapped to PCDH15 locus on chromosome 10q21.1. Three different point mutations in exon 11 of PCDH15 were identified and one of them, c.1304A>C was found to be segregating with the disease phenotype in Pakistani family with Usher phenotype. This, c.1304A>C transversion mutation predicts an amino-acid substitution of aspartic acid with an alanine at residue number 435 (p.D435A) of its protein product. Moreover, in silico analysis revealed conservation of aspartic acid at position 435 and predicated this change as pathogenic. The identification of c.1304A>C pathogenic mutation in PCDH15 gene and its association with Usher syndrome in a consanguineous Pakistani family is the first example of a missense mutation of PCDH15 causing USH1 phenotype. In previous reports, it was hypothesized that severe mutations such as truncated protein of PCDH15 led to the Usher I phenotype and that missense variants are mainly responsible for non-syndromic hearing impairment.

The changing pattern and determinants of declining consanguinity in Jordan during 1990-2012.

PubMed

Islam, M Mazharul

2018-03-01

Consanguinity is a deep rooted cultural trait in Jordan. To examine the patterns and determinants of declining rates of consanguineous marriage in Jordan during 1990-2012 in the context of the changing pattern of socio-economic and demographic conditions. The data come from the 1990 and 2012 Jordan Population and Family Health Surveys (JPFHSs). A total of 6461 women in 1990 and 11,352 women in 2012 were successfully interviewed. Descriptive and multivariate statistical techniques were used for data analysis. Consanguinity was found to be widely practiced (35% in 2012) until recent times in Jordan. However, there has been a secular declining trend over the last few decades as the practice of consanguinity has declined from 56% in 1990 to 35% in 2012. Increasing age at marriage and female education, higher level of education of husbands, declining family size, increasing rate of urbanisation and female employment, exposure to mass media and higher economic status appeared as significant predictors of declining consanguinity in Jordan. The findings of this study support Goode's hypothesis of a decrease of consanguinity with modernisation. Although consanguinity is a deeply rooted cultural trend in Jordan, it is gradually losing ground due to modernisation and socio-demographic transition of the country.

X-linked juvenile retinoschisis in a consanguineous family: phenotypic variability and report of a homozygous female patient.

PubMed

Gliem, Martin; Holz, Frank G; Stöhr, Heidi; Weber, Bernhard H F; Charbel Issa, Peter

2014-12-01

To describe the phenotypic variability in a consanguineous family with genetically confirmed X-linked retinoschisis. Five patients, including one homozygous female, were characterized by clinical examination, optical coherence tomography, fundus autofluorescence, mapping of macular pigment optical density, electroretinography, and DNA testing. The 36-year-old male index patient showed a ring of enhanced autofluorescence and outer retinal atrophy on optical coherence tomography. Electroretinography testing revealed a reduced a/b ratio. His mother presented with a central atrophic retina with markedly reduced autofluorescence signal and a surrounding ring of enhanced autofluorescence. The 40-year-old brother of the index patient and his 2 sons showed characteristic signs for X-linked retinoschisis, including retinal schisis and a reduced a/b ratio. Genetic testing revealed a c.293C>A mutation in the RS1 gene in all affected family members while the mother of the index patient was homozygous for this mutation. X-linked retinoschisis can present with a wide phenotypic variability. Here, detailed family history and genetic testing established the diagnosis of X-linked retinoschisis despite striking differences in phenotypic presentation in affected subjects, homozygosity of one affected female, and seemingly dominant inheritance in three subsequent generations because of multiple consanguinity.

The frequency of consanguineous marriage in eastern Turkey.

PubMed

Akbayram, S; Sari, N; Akgün, C; Doğan, M; Tuncer, O; Caksen, H; Oner, A F

2009-01-01

The frequency of consanguineous marriage in Eastern Turkey: The rate of consanguineous marriage (CM) varies depended on different factors such as race, characteristics of population, and religion and moral features in different countries. Gene frequency and genetic structure are changed by CMs. The aim of the present study is to assess the prevalence of CM and its effects on miscarriage, stillbirth, congenital malformation and ratio of newborn death. This study was performed in Van region, Eastern Turkey, between September 2005 and April 2006. A total of 650 families from 24 districts chosen in accordance with the number of inhabitants were included in this study. First cousin marriages were accepted as a first degree CMs, sesquialter and second cousin marriages as second degree and marriages between distant relatives were accepted as a third degree CM. Monthly income of the families was classified in accordance with minimum wage determined by government. Of all families, 224 (34.4%) had CM, and 168 (75%) had first-degree consanguinity. A lower CM rate was found in mothers who graduated from secondary school or upgrading (p < 0.01). However, no relationship was found between CM and fathers' education level. While a low CM rate was found in families who had two or less children (p < 0.01), high rate was observed in families who had five or more children. In addition, a high rate of miscarriage, stillbirth and mental-motor retardation was found in families with CM (p < 0.05). The rate of child mortality between the aged 0-2 years was found to be higher in families with CM (p < 0.01). The higher CM rate was observed in families who married due to pressure or insistence of their families than married voluntarily (p < 0.05). Our study showed that CM rate was very high, 34.4%, in our region Eastern Turkey.

Search for consanguinity within and among families of patients with trichothiodystrophy associated with xeroderma pigmentosum.

PubMed Central

Nuzzo, F; Zei, G; Stefanini, M; Colognola, R; Santachiara, A S; Lagomarsini, P; Marinoni, S; Salvaneschi, L

1990-01-01

The association of two rare hereditary disorders, trichothiodystrophy (TTD) and xeroderma pigmentosum (XP), was found in four patients from three families, apparently unrelated but living in the same geographical area. In order to test the hypothesis of a common ancestor, consanguinity within and among the families was checked using three different approaches: reconstruction of genealogical trees, typing of blood markers, and surname analysis. The results of the three types of analyses strengthen the hypothesis that, in at least two out of the three families, the genetic defect determining the TTD/XP phenotype is identical by descent, as a consequence of remote inbreeding. This implies that if two mutations are responsible for the two diseases they are at linked loci or affect the same gene. PMID:2308151

[Spectrum of congenital malformations observed in neonates of consanguineous parents].

PubMed

Pinto Escalante, D; Castillo Zapata, I; Ruiz Allec, D; Ceballos Quintal, J M

2006-01-01

Consanguineous unions occur in all populations around the world. Couples related as second cousins or closer have been observed with deleterious effect. Among the clinical effects of parental consanguinity, the incidence of offspring with congenital malformations (CM) increases approximately two-fold. A hospital database of neonates with CM was searched to select neonates with parental consanguinity and two control groups. One control group consisted of healthy neonates and the other control group consisted of neonates with CM but without parental consanguinity. Both control groups consisted of the first neonate of the same sex to be born after a consanguineous neonate with CM. Family, sociodemographic and anthropometric variables, as well as the severity of the malformations, were compared between the two groups with CM. Neonates with CM were grouped into five categories: Major multiple CM, minor multiple CM, isolated major CM, isolated minor CM, and specific diseases. The indigenous Mayan subpopulation was also analyzed. Among 1117 neonates with CM, parental consanguinity was found in 21. Parental consanguinity was also found in 8 neonates in the group of healthy controls (OR 2.4 [1.05-5.95]). The most common form of consanguinity was between second cousins and was more frequent in the Mayan subpopulation. Major multiple CM were more frequent among consanguineous than among nonconsanguineous couples. No association was found between the severity of CM and the degree of relationship. The prevalence of consanguinity found in neonates with CM and healthy controls (1.9 % and 0.8 %) was similar to that found in other Latin populations. A higher prevalence was found in the Mayan population. Mayor multiple CM were more frequent among the neonates of consanguineous than among nonconsanguineous couples.

Constitutional Mismatch Repair Deficiency in Israel: High Proportion of Founder Mutations in MMR Genes and Consanguinity.

PubMed

Baris, Hagit N; Barnes-Kedar, Inbal; Toledano, Helen; Halpern, Marisa; Hershkovitz, Dov; Lossos, Alexander; Lerer, Israela; Peretz, Tamar; Kariv, Revital; Cohen, Shlomi; Half, Elizabeth E; Magal, Nurit; Drasinover, Valerie; Wimmer, Katharina; Goldberg, Yael; Bercovich, Dani; Levi, Zohar

2016-03-01

Heterozygous germline mutations in any of the mismatch repair (MMR) genes, MLH1, MSH2, MSH6, and PMS2, cause Lynch syndrome (LS), an autosomal dominant cancer predisposition syndrome conferring a high risk of colorectal, endometrial, and other cancers in adulthood. Offspring of couples where both spouses have LS have a 1:4 risk of inheriting biallelic MMR gene mutations. These cause constitutional MMR deficiency (CMMRD) syndrome, a severe recessively inherited cancer syndrome with a broad tumor spectrum including mainly hematological malignancies, brain tumors, and colon cancer in childhood and adolescence. Many CMMRD children also present with café au lait spots and axillary freckling mimicking neurofibromatosis type 1. We describe our experience in seven CMMRD families demonstrating the role and importance of founder mutations and consanguinity on its prevalence. Clinical presentations included brain tumors, colon cancer, lymphoma, and small bowel cancer. In children from two nonconsanguineous Ashkenazi Jewish (AJ) families, the common Ashkenazi founder mutations were detected; these were homozygous in one family and compound heterozygous in the other. In four consanguineous families of various ancestries, different homozygous mutations were identified. In a nonconsanguineous Caucasus/AJ family, lack of PMS2 was demonstrated in tumor and normal tissues; however, mutations were not identified. CMMRD is rare, but, especially in areas where founder mutations for LS and consanguinity are common, pediatricians should be aware of it since they are the first to encounter these children. Early diagnosis will enable tailored cancer surveillance in the entire family and a discussion regarding prenatal genetic diagnosis. © 2015 Wiley Periodicals, Inc.

Addressing key issues in the consanguinity-related risk of autosomal recessive disorders in consanguineous communities: lessons from a qualitative study of British Pakistanis.

PubMed

Darr, A; Small, N; Ahmad, W I U; Atkin, K; Corry, P; Modell, B

2016-01-01

Currently, there is no consensus regarding services required to help families with consanguineous marriages manage their increased genetic reproductive risk. Genetic services for communities with a preference for consanguineous marriage in the UK remain patchy, often poor. Receiving two disparate explanations of the cause of recessive disorders (cousin marriage and recessive inheritance) leads to confusion among families. Further, the realisation that couples in non-consanguineous relationships have affected children leads to mistrust of professional advice. British Pakistani families at-risk for recessive disorders lack an understanding of recessive disorders and their inheritance. Such an understanding is empowering and can be shared within the extended family to enable informed choice. In a three-site qualitative study of British Pakistanis, we explored family and health professional perspectives on recessively inherited conditions. Our findings suggest, firstly, that family networks hold strong potential for cascading genetic information, making the adoption of a family-centred approach an efficient strategy for this community. However, this is dependent on provision of high-quality and timely information from health care providers. Secondly, families' experience was of ill-coordinated and time-starved services, with few having access to specialist provision from Regional Genetics Services; these perspectives were consistent with health professionals' views of services. Thirdly, we confirm previous findings that genetic information is difficult to communicate and comprehend, further complicated by the need to communicate the relationship between cousin marriage and recessive disorders. A communication tool we developed and piloted is described and offered as a useful resource for communicating complex genetic information.

A Homozygous TPO Gene Duplication (c.1184_1187dup4) Causes Congenital Hypothyroidism in Three Siblings Born to a Consanguineous Family

PubMed Central

Cangul, Hakan; Aydin, Banu K.; Bas, Firdevs

2015-01-01

Congenital hypothyroidism (CH) is the most common neonatal endocrine disease, and germ-line mutations in the TPO gene cause the inherited form of the disease. Our aim in this study was to determine the genetic basis of congenital hypothyroidism in three affected children coming from a consanguineous Turkish family. Because CH is usually inherited in autosomal recessive manner in consanguineous/multicase families, we adopted a two-stage strategy of genetic linkage studies and targeted sequencing of the candidate genes. First, we investigated the potential genetic linkage of the family to any known CH locus, using microsatellite markers, and then screened for mutations in linked-gene by conventional sequencing. The family showed potential linkage to the TPO gene and we detected a homozygous duplication (c.1184_1187dup4) in all cases. The mutation segregated with disease status in the family. This study confirms the pathogenicity of the c.1184_1187dup4 mutation in the TPO gene and helps establish a genotype/phenotype correlation associated with this mutation. It also highlights the importance of molecular genetic studies in the definitive diagnosis and accurate classification of CH. PMID:27617131

Splice-site mutations identified in PDE6A responsible for retinitis pigmentosa in consanguineous Pakistani families

PubMed Central

Khan, Shahid Y.; Ali, Shahbaz; Naeem, Muhammad Asif; Khan, Shaheen N.; Husnain, Tayyab; Butt, Nadeem H.; Qazi, Zaheeruddin A.; Akram, Javed; Riazuddin, Sheikh; Ayyagari, Radha; Hejtmancik, J. Fielding

2015-01-01

Purpose This study was conducted to localize and identify causal mutations associated with autosomal recessive retinitis pigmentosa (RP) in consanguineous familial cases of Pakistani origin. Methods Ophthalmic examinations that included funduscopy and electroretinography (ERG) were performed to confirm the affectation status. Blood samples were collected from all participating individuals, and genomic DNA was extracted. A genome-wide scan was performed, and two-point logarithm of odds (LOD) scores were calculated. Sanger sequencing was performed to identify the causative variants. Subsequently, we performed whole exome sequencing to rule out the possibility of a second causal variant within the linkage interval. Sequence conservation was performed with alignment analyses of PDE6A orthologs, and in silico splicing analysis was completed with Human Splicing Finder version 2.4.1. Results A large multigenerational consanguineous family diagnosed with early-onset RP was ascertained. An ophthalmic clinical examination consisting of fundus photography and electroretinography confirmed the diagnosis of RP. A genome-wide scan was performed, and suggestive two-point LOD scores were observed with markers on chromosome 5q. Haplotype analyses identified the region; however, the region did not segregate with the disease phenotype in the family. Subsequently, we performed a second genome-wide scan that excluded the entire genome except the chromosome 5q region harboring PDE6A. Next-generation whole exome sequencing identified a splice acceptor site mutation in intron 16: c.2028–1G>A, which was completely conserved in PDE6A orthologs and was absent in ethnically matched 350 control chromosomes, the 1000 Genomes database, and the NHLBI Exome Sequencing Project. Subsequently, we investigated our entire cohort of RP familial cases and identified a second family who harbored a splice acceptor site mutation in intron 10: c.1408–2A>G. In silico analysis suggested that these

[Analysis of clinical phenotype and mode of inheritance in retinitis pigmentosa patients with consanguineous marriage].

PubMed

Rong, Wei-ning; Sheng, Xun-lun; Liu, Ya-ni

2012-10-01

To analyse the mode of inheritance and clinical characteristics of retinitis pigmentosa (RP) patients with consanguineous marriage. RP patients were recruited for this study in Ningxia Eye Hospital from September 2009 to July 2011. All patients received complete ophthalmic examination. The mode of inheritance were determined based on family history and marriage history. Clinical features were characterized by complete ophthalmic examinations including visual acuity, macular OCT, visual field and electroretinogram (ERG). A total of 143 individuals with RP (33 families) were recruited. Based on analysis of family history and marriage history, 20 RP families (23 patients) had consanguineous marriage history accounted for 60.6% RP families (16.1% RP patients). There were 4 patients (from 4 families) diagnosed as Usher syndrome. In 20 RP families with consanguineous marriage history, 7 families (35.0%) were Hui ethnicity and 13 families (65%) were Han ethnicity. The marriages of 15 families were between first cousins and 3 families were between second cousins, only 2 families were between half cousins matrimony. Of 23 RP patients, 12 were males and 11 were females. The average age of onset was 11.4 ± 6.8 years and the average age of recruitment was (32.0 ± 13.5) years. The best-corrected visual acuity was less than 0.6 in 78.2% patients. According to the features of the fundus, 13 patients were classical retinitis pigmentosa and 10 patients were retinitis pigmentosa sine pigmento. Visual field examination showed that all patients had varying degrees of peripheral visual field defect. Retinal neuroepithelial layer of macular and peripheral retina became thinner and retinal photoreceptors were disappeared. The average thickness of macular fovea was (186.1 ± 78.7) µm on right eyes and (187.4 ± 76.3) µm on left eyes. The incidence of RP with consanguineous marriages was high in Ningxia Region. The mode of inheritance of RP patients with consanguinity is autosomal

Consanguinity and primary immunodeficiencies.

PubMed

Al-Herz, Waleed; Aldhekri, Hasan; Barbouche, Mohamed-Ridha; Rezaei, Nima

2014-01-01

Primary immunodeficiencies (PIDs) are a heterogeneous group of genetic disorders caused by defects in the immune system that predispose patients to infections, autoimmune diseases, lymphoproliferation and malignancies. Most PIDs are inherited in an autosomal recessive pattern; therefore, they are more common in areas with high rates of consanguineous marriage. Reports about PIDs from these areas have demonstrated a peculiar prevalence of more severe forms of diseases compared to other regions, and patients born to consanguineous parents have increased rates of morbidity and mortality compared to other patients. Individuals at high risk of having a child with a PID who wish to have a healthy child have limited options, these include prenatal diagnosis and pre-implantation genetic diagnosis. However, these options require a collaborative team of specialists and may not always be implemented due to geographic, religious, financial or social factors. The recent introduction of newborn-screening programs for a number of T and B lymphocyte deficiencies will facilitate early diagnosis and therapeutic interventions, which may include hematopoietic stem cell transplantation and intravenous immunoglobulin treatment. There is a need for the implementation of strategies to increase public awareness of the health risks associated with consanguineous marriage. It should be stressed that genetic counseling should be an important component of the care of patients with PIDs as well as their families. © 2014 S. Karger AG, Basel.

THE CAUSAL RELATIONSHIP BETWEEN CONSANGUINEOUS MARRIAGES AND INFANT MORTALITY IN TURKEY.

PubMed

Koç, İsmet; Eryurt, Mehmet Alİ

2017-07-01

Turkey has high levels of infant mortality and consanguineous marriages. It has had a high level of infant mortality for its economic level for many years. Over recent decades, although adult mortality rates have not been very different from those of other countries with similar socioeconomic structures, its life expectancy at birth has remained low due to its high infant mortality rate. This has been called the Turkish Puzzle. According to the Turkey Family Structure and Population Issues Survey, 27% of women had a consanguineous marriage in 1968. Subsequent Turkish Demographic and Health Surveys (TDHSs) found the rate of consanguineous marriages to be stagnated at 22-24%, with a resistance to reduction. According to the TDHS-2008, 24% of women had a consanguineous marriage. Numerous studies in various countries of the world have indicated that consanguineous marriages, particularly of first-degree, have the effect of increasing infant mortality. The main aim of this study was to assess the causal impact of consanguineous, particularly first-degree consanguineous, marriages on infant mortality, controlling for individual, cultural, bio-demographic and environmental factors. Data were merged from four Turkish DHS data sets (1993, 1998, 2003 and 2008). Multivariate analysis revealed that first-degree consanguineous marriages have increased infant mortality by 45% in Turkey: 57% in urban areas and 39% in rural areas. The results indicate that there is a causal relationship between consanguineous marriages and infant mortality. This finding should be taken into account when planning policies to reduce infant mortality in Turkey, and in other countries with high rates of consanguineous marriage and infant mortality.

Effects of consanguineous marriage on reproductive behaviour, adverse pregnancy outcomes and offspring mortality in Oman.

PubMed

Islam, M Mazharul

2013-05-01

The long tradition of high prevalence of consanguineous marriages in Omani society may have ramifications for reproductive behaviour and health of offspring. To examine the relevance of consanguinity to reproductive behaviour, adverse pregnancy outcome and offspring mortality in Oman. The data analysed came from the 2000 Oman National Health Survey. Selected indicators that are related to reproductive behaviour, adverse pregnancy outcome and offspring mortality were considered as explanatory variables. Various statistical methods and tests were used for data analysis. Consanguineous marriage was found to be associated with lower age at first birth, higher preference for larger family size, lower level of husband-wife communication about use of family planning methods and lower rate of contraceptive use. Although bivariate analysis showed elevated fertility and childhood mortality among the women with consanguineous marriage, after controlling for relevant socio-demographic factors in multivariate analysis, fertility, childhood mortality and foetal loss showed no significant association with consanguinity in Oman. Consanguinity plays an important role in determining some of the aspects of reproduction and health of newborns, but did not show any detrimental effects on fertility and offspring mortality. The high level of consanguinity and its relevance to reproduction in Oman need to be considered in its public health strategy in a culturally acceptable manner.

Consanguineous marriage in Oman: understanding the community awareness about congenital effects of and attitude towards consanguineous marriage.

PubMed

Mazharul Islam, M

2017-05-01

Although consanguinity is widely practiced in Oman, the attitude of community towards consanguinity and the awareness of its health consequences to offspring remain largely unexplored. To analyse the levels and trends of consanguineous marriage and examine community awareness about congenital anomaly associated with consanguinity and attitude towards consanguinity in Oman. The data come from a nationally representative survey on Omani adults of age 18 years and above, irrespective of their marital status. Data were analysed using both descriptive and multivariate statistical techniques. The survey results indicate a very high rate (49%) of consanguineous marriage in Oman. There is a declining trend in consanguinity which may be attributed to decline in first cousin marriage. Omani adults have moderately high knowledge (69%) about health consequences of consanguineous marriage. There is a high positive attitude towards consanguineous marriage (75%) which appeared as a significant predictor of current practice of consanguineous marriage in Oman. The positive attitude of the Omani community towards consanguinity outweighs the negative health consequences of consanguinity, and the practice is likely to remain high in the near future. Strong educational and motivational programmes are needed to bring further changes in attitude towards consanguinity and, thus, reduce the burden of congenital anomalies associated with consanguinity in Oman.

Usher syndrome in four siblings from a consanguineous family of Pakistani origin.

PubMed

Trop, I; Schloss, M D; Polomeno, R; Der Kaloustian, V

1995-04-01

Usher syndrome is a heterogeneous group of disorders of autosomal recessive inheritance characterized by retinitis pigmentosa and congenital sensorineural hearing loss. Two types are accepted clinically: type I is associated with profound congenital deafness with progressive pigmentary retinopathy and total loss of vestibular function. Type II is a milder form, with moderate-to-profound hearing loss and a milder form of retinitis pigmentosa. Vestibular function is preserved. A total of five loci have been identified as accounting for the two distinct phenotypic presentations. We describe a consanguineous family of Pakistani origin whose four children all are affected with Usher syndrome type I. DNA analysis showed non-linkage to any of the loci already identified as tightly linked to the Usher syndrome type I.

Consanguinity and dysmorphology in Arabs.

PubMed

Al-Gazali, Lihadh; Hamamy, Hanan

2014-01-01

Incidence rates of congenital disorders among the 350 million inhabitants of Arab countries could be influenced via the people's demographic and cultural characteristics. Arabs usually marry at a young age and have large families. They share certain core cultural values and beliefs, with the family accepted as the central structure of society. Consanguineous marriage is favored and respected in most if not all Arab communities, and intrafamilial unions currently account for 20-50% of all marriages. First-cousin unions are especially popular and constitute almost one quarter of all marriages in many Arab countries. Consequently, autosomal recessive (AR) dysmorphic syndromes constitute a considerable proportion of all birth defects among Arabs. Arab geneticists, with their persistent commitment to advancing research, have contributed to the description of a number of rare and new AR syndromes with the identification of novel genes. The collaboration with research teams in high-income countries resulted in a plethora of data on pathogenic variants and their function in causing dysmorphic syndromes. There could still be a considerable number of rare dysmorphic syndromes that prevail among Arabs which are not hitherto described and whose underlying molecular pathologies are not yet defined. Arab countries should thus strive to deploy DNA diagnostics and to build research capability around local priorities. Furthermore, a characterization of the prevailing genetic disorders in each geographic location, together with their mutations, is needed to plan for appropriate screening and testing protocols. An overview of consanguinity in Arab countries and examples of dysmorphology syndromes associated with consanguinity with their available molecular bases will be discussed. © 2014 S. Karger AG, Basel

Consanguinity in two Uruguayan cities: historical evolution and characteristics (1800--1994).

PubMed

Lusiardo, A; Barreto, I; Hidalgo, P C; Bonilla, C; Bertoni, B; Portas, M; Sans, M

2004-01-01

Information about consanguinity in Uruguay is scarce and limited to the end of the 20th century. To determine the frequency and characteristics of consanguineous marriages, as well as chronological trends, in two Uruguayan cities over almost two centuries. We analysed 28,393 Roman Catholic Church marriage records and Diocesan consanguinity dispensations belonging to the cities of Melo (Northeast), and Montevideo (South), for the period 1800--1994. 633 (2.23%) marriages were consanguineous. Among them, first cousin marriages were the most common (58.8% of all consanguineous marriages, including double consanguineous), especially those where the bride and groom were related through their maternal side. During the first decades of the 19th century both regions showed low levels of consanguinity. Consanguinity reached its maximum during the mid-1800s and decreased significantly throughout the 20th century. The overall mean coefficients of inbreeding were moderate in both cases, being greater in the Northeast (alpha=0.00165) than in the South (alpha = 0.00089). The low level of consanguinity as well as the structure of consanguineous marriages (distribution by degrees) is similar to that found in other southern South American countries. Temporal trends are similar to those found in industrialized regions in Europe, with maximum inbreeding levels during the middle-late 19th century; however, the clear predominance of first cousin unions, differs from most of the data for European countries. Small differences between the two cities can be related to diverse facts, such as socio-economic conditions, ethnic origin, immigration, and sampling.

APOA5 Q97X mutation identified through homozygosity mapping causes severe hypertriglyceridemia in a Chilean consanguineous family.

PubMed

Dussaillant, Catalina; Serrano, Valentina; Maiz, Alberto; Eyheramendy, Susana; Cataldo, Luis Rodrigo; Chavez, Matías; Smalley, Susan V; Fuentes, Marcela; Rigotti, Attilio; Rubio, Lorena; Lagos, Carlos F; Martinez, José Alfredo; Santos, José Luis

2012-11-15

Severe hypertriglyceridemia (HTG) has been linked to defects in LPL, APOC2, APOA5, LMF1 and GBIHBP1 genes. However, a number of severe HTG cases are probably caused by as yet unidentified mutations. Very high triglyceride plasma levels (>112 mmol/L at diagnosis) were found in two sisters of a Chilean consanguineous family, which is strongly suggestive of a recessive highly penetrant mutation. The aim of this study was to determine the genetic locus responsible for the severe HTG in this family. We carried out a genome-wide linkage study with nearly 300,000 biallelic markers (Illumina Human CytoSNP-12 panel). Using the homozygosity mapping strategy, we searched for chromosome regions with excess of homozygous genotypes in the affected cases compared to non-affected relatives. A large homozygous segment was found in the long arm of chromosome 11, with more than 2,500 consecutive homozygous SNP shared by the proband with her affected sister, and containing the APOA5/A4/C3/A1 cluster. Direct sequencing of the APOA5 gene revealed a known homozygous nonsense Q97X mutation (p.Gln97Ter) found in both affected sisters but not in non-affected relatives nor in a sample of unrelated controls. The Q97X mutation of the APOA5 gene in homozygous status is responsible for the severe hypertriglyceridemia in this family. We have shown that homozygosity mapping correctly pinpointed the genomic region containing the gene responsible for severe hypertriglyceridemia in this consanguineous Chilean family.

APOA5 Q97X Mutation Identified through homozygosity mapping causes severe hypertriglyceridemia in a Chilean consanguineous family

PubMed Central

2012-01-01

Background Severe hypertriglyceridemia (HTG) has been linked to defects in LPL, APOC2, APOA5, LMF1 and GBIHBP1 genes. However, a number of severe HTG cases are probably caused by as yet unidentified mutations. Very high triglyceride plasma levels (>112 mmol/L at diagnosis) were found in two sisters of a Chilean consanguineous family, which is strongly suggestive of a recessive highly penetrant mutation. The aim of this study was to determine the genetic locus responsible for the severe HTG in this family. Methods We carried out a genome-wide linkage study with nearly 300,000 biallelic markers (Illumina Human CytoSNP-12 panel). Using the homozygosity mapping strategy, we searched for chromosome regions with excess of homozygous genotypes in the affected cases compared to non-affected relatives. Results A large homozygous segment was found in the long arm of chromosome 11, with more than 2,500 consecutive homozygous SNP shared by the proband with her affected sister, and containing the APOA5/A4/C3/A1 cluster. Direct sequencing of the APOA5 gene revealed a known homozygous nonsense Q97X mutation (p.Gln97Ter) found in both affected sisters but not in non-affected relatives nor in a sample of unrelated controls. Conclusion The Q97X mutation of the APOA5 gene in homozygous status is responsible for the severe hypertriglyceridemia in this family. We have shown that homozygosity mapping correctly pinpointed the genomic region containing the gene responsible for severe hypertriglyceridemia in this consanguineous Chilean family. PMID:23151256

Consanguinity and isolated atrial septal defect in North East of Iran.

PubMed

Moghaddam, Hasan Mottaghi; Esfehani, Reza Jafarzadeh; Panah, Nader Yazdan; Esfehani, Ali Jafarzadeh

2014-01-01

The rate of consanguineous marriage is high in Middle Eastern countries such as Iran. The relationship between consanguineous marriage and congenital heart disease is discussed in some studies, but there is not much data for relationship between atrial septal defect (ASD) and consanguineous marriage. The aim of this study was to evaluate the relationship between consanguineous marriage and ASD echocardiographic characteristics. This was a cross-sectional study approved by Mashhad University of Medical Sciences ethics committee and took place in Mashhad, Iran, for a period of 3 years from August 2008 till September 2011. In this cross-sectional study, 113 ASD patients participated and they were categorized into 3 groups on the basis of family relationship between their parents: first group-"no relationship," second group- "third degree relationship," and third group- "far relationship." Among the 54 male and 59 female ASD patients, the most prevalent type of ASD was ASD secundum (85.0%) followed by sinus venosus (8.8%). A total of 56% patients were present in the first group and 15% and 29% in the second group and the third group, respectively." The relationship between consanguinity and type of ASD (P < .001) and gender (P < .001 each) was observed. The relationship between the age of onset of disease and consanguinity (P=.003) was also observed. Considering the fact that there is a high prevalence of ASD and consanguineous marriage in Iran and bearing in mind the results of the present study, we recommend educating couples about the outcomes of consanguineous marriage in pre-marriage counseling.

Molecular genetic analysis of consanguineous Pakistani families with autosomal recessive hypohidrotic ectodermal dysplasia.

PubMed

Bibi, Nosheen; Ahmad, Saeed; Ahmad, Wasim; Naeem, Muhammad

2011-02-01

Hypohidrotic ectodermal dysplasia is an inherited disorder characterized by defective development of teeth, hairs and sweat glands. X-linked hypohidrotic ectodermal dysplasia is caused by mutations in the EDA gene, and autosomal forms of hypohidrotic ectodermal dysplasia are caused by mutations in either the EDAR or the EDARADD genes. To study the molecular genetic cause of autosomal recessive hypohidrotic ectodermal dysplasia in three consanguineous Pakistani families (A, B and C), genotyping of 13 individuals was carried out by using polymorphic microsatellite markers that are closely linked to the EDAR gene on chromosome 2q11-q13 and the EDARADD gene on chromosome 1q42.2-q43. The results revealed linkage in the three families to the EDAR locus. Sequence analysis of the coding exons and splice junctions of the EDAR gene revealed two mutations: a novel non-sense mutation (p.E124X) in the probands of families A and B and a missense mutation (p.G382S) in the proband of family C. In addition, two synonymous single-nucleotide polymorphisms were also identified. The finding of mutations in Pakistani families extends the body of evidence that supports the importance of EDAR for the development of hypohidrotic ectodermal dysplasia. © 2010 The Authors. Australasian Journal of Dermatology © 2010 The Australasian College of Dermatologists.

Junctional epidermolysis bullosa in the Middle East: clinical and genetic studies in a series of consanguineous families.

PubMed

Nakano, Aoi; Lestringant, Gilles G; Paperna, Tamar; Bergman, Reuven; Gershoni, Ruth; Frossard, Philippe; Kanaan, Moien; Meneguzzi, Guerrino; Richard, Gabriele; Pfendner, Ellen; Uitto, Jouni; Pulkkinen, Leena; Sprecher, Eli

2002-04-01

Junctional epidermolysis bullosa (JEB) is a group of inherited blistering diseases characterized by epidermal-dermal separation resulting from mutations that affect the function of critical components of the basement membrane zone. This group of autosomal recessive diseases is especially prevalent in regions where consanguinity is common, such as the Middle East. However, the clinical and genetic epidemiology of JEB in this region remains largely unexplored. The aim of the present study was to assess a series of consanguineous JEB families originating from the Middle East. We identified 7 families referred to us between 1998 and 1999 and originating from the United Arab Emirates, Saudi Arabia, Sudan, Yemen, and Israel. Histologic, immunofluorescence, and electron microscopy studies were performed to direct the subsequent molecular analysis. DNA obtained from all family members was amplified by means of polymerase chain reaction and analyzed by conformation-sensitive gel electrophoresis with subsequent direct sequencing. In 6 families presenting with the clinical and histologic features distinctive for JEB, mutations in genes encoding 1 of the 3 subunit polypeptides of laminin-5 were identified. Two families each had mutations in LAMB3, 2 in LAMA3, and 2 in LAMC2. Out of 7 distinct mutations, 5 were novel and 2 were recurrent. No relationship was found between the presence of nonsense/frameshift mutations in laminin-5 genes and perinatal mortality, contradicting a major genotype-phenotype correlation previously reported in the European and US literature. Similarly, none of the recurrent LAMB3 hot spot mutations previously described in other populations was found in our series. Finally, in a family with the clinical diagnosis of generalized atrophic benign epidermolysis bullosa, a homozygous non-sense mutation in Col17A1 gene (encoding the BPAG2 antigen) was identified. The present report suggests (1) the existence of a unique spectrum of mutations in the Middle East

Consanguinity, endogamy and inborn errors of metabolism in Oman: a cross-sectional study.

PubMed

Al-Thihli, Khalid; Al-Murshedi, Fathiya; Al-Hashmi, Nadia; Al-Mamari, Watfa; Islam, M Mazharul; Al-Yahyaee, Said A

2014-01-01

The Sultanate of Oman, like many other Arab countries, has relatively high rates of consanguinity. Reports suggest that the incidence of inborn errors of metabolism (IEM) is also high in Oman. This retrospective cross-sectional study was designed to evaluate the number of patients with IEM being followed at the only two tertiary centers in Oman treating such patients, and to calculate the consanguinity rates among these families. The electronic medical records of all patients were reviewed for demographic and clinical characteristics. A total of 285 patients with IEM were being followed at the 2 centers involved; 162 (56.8%) were male and 123 (43.2%) were female. The history of consanguinity was documented or available for 241 patients: 229 patients (95%) were born to consanguineous parents related as second cousins or closer. First-cousin marriages were reported in 191 families (79.3%), while 31 patients (12.9%) were born to second cousins. The parents of 5 patients (2%) were related as double first cousins, and 2 patients (1%) were born to first cousins once removed. The average coefficient of inbreeding (F) in our study was 0.081. Seventeen patients (6%) had associated comorbid conditions other than IEM. Our study highlights the clinical burden of IEM in Oman and emphasizes the high consanguinity rates among the parents of affected patients. © 2014 S. Karger AG, Basel

Consanguineous marriage and reproductive risk: attitudes and understanding of ethnic groups practising consanguinity in Western society.

PubMed

Teeuw, Marieke E; Loukili, Ghariba; Bartels, Edien Ac; ten Kate, Leo P; Cornel, Martina C; Henneman, Lidewij

2014-04-01

Consanguineous couples should be adequately informed about their increased reproductive risk and possibilities for genetic counselling. Information may only be effective if it meets the needs of the target group. This study aimed to gain more insight into: (1) attitudes of people belonging to ethnic groups in Western society towards consanguinity and their understanding of risk for offspring; and (2) their attitudes regarding reproductive information targeted at consanguineous couples. Dutch Moroccans and Turks were invited to complete an online questionnaire by snowball sampling and by placing a link on two popular Dutch Moroccan/Turkish forum websites between September and October 2011. The questionnaire was completed by 201 individuals who were, on average, neither positive nor negative towards consanguinity. Respondents with a consanguineous partner were more positive, estimated the risk for the offspring lower and were less positive about the provision of risk information to consanguineous couples when compared with respondents without a consanguineous partner. Participants of Turkish origin had a more negative attitude towards consanguinity and estimated the reproductive risk higher than Moroccan participants. More than half of the respondents thought that information should be given before marriage, whereas only 10% thought it should never be provided. The general practitioner was most often mentioned (54%) as the designated professional to inform people. Information about genetic risks related to consanguinity should be offered early, preferably before marriage. The diversity of the target population requires various strategies to disseminate information and reach consanguineous couples with the offer of genetic counselling.

Consanguineous marriage and reproductive risk: attitudes and understanding of ethnic groups practising consanguinity in Western society

PubMed Central

Teeuw, Marieke E; Loukili, Ghariba; Bartels, Edien AC; ten Kate, Leo P; Cornel, Martina C; Henneman, Lidewij

2014-01-01

Consanguineous couples should be adequately informed about their increased reproductive risk and possibilities for genetic counselling. Information may only be effective if it meets the needs of the target group. This study aimed to gain more insight into: (1) attitudes of people belonging to ethnic groups in Western society towards consanguinity and their understanding of risk for offspring; and (2) their attitudes regarding reproductive information targeted at consanguineous couples. Dutch Moroccans and Turks were invited to complete an online questionnaire by snowball sampling and by placing a link on two popular Dutch Moroccan/Turkish forum websites between September and October 2011. The questionnaire was completed by 201 individuals who were, on average, neither positive nor negative towards consanguinity. Respondents with a consanguineous partner were more positive, estimated the risk for the offspring lower and were less positive about the provision of risk information to consanguineous couples when compared with respondents without a consanguineous partner. Participants of Turkish origin had a more negative attitude towards consanguinity and estimated the reproductive risk higher than Moroccan participants. More than half of the respondents thought that information should be given before marriage, whereas only 10% thought it should never be provided. The general practitioner was most often mentioned (54%) as the designated professional to inform people. Information about genetic risks related to consanguinity should be offered early, preferably before marriage. The diversity of the target population requires various strategies to disseminate information and reach consanguineous couples with the offer of genetic counselling. PMID:23921534

Social structure and consanguinity in a French mountain Population (1550-1849).

PubMed

Rabino-Massa, Emma; Prost, Michel; Boëtsch, Gilles

2005-04-01

Sociocultural factors play a crucial role in the variation of consanguinity in a population. The choice of specific matrimonial strategies can favor the closure or opening of the group to the outside, whereas differential fertility affects the gene flow from one generation to another. In the present study we analyzed the role of socioprofessional groups in the maintenance of endogamy and consanguinity in a French Alpine valley: Vallouise in the Briançon area. In mountain environments, where the reproductive space is limited and quickly saturated, the autochthonous families adopt diversified matrimonial strategies. These marriage practices tend to prevent fragmentation of agricultural property. We analyzed the matrimonial behavior in the two main social groups of this population (décideurs and farmers) from 1550 to 1849. To better understand the behavior of the two social groups, we considered the two components of consanguinity, close and distant. Our study showed that the two groups had similar behavior regarding consanguinity. The way to prevent fragmentation of the patrimony was to choose a consanguineous spouse. This type of strategy inevitably leads to a high percentage of endogamy, which in this region of the Alps exceeded 90% through many centuries.

Consanguinity in Lebanon: prevalence, distribution and determinants.

PubMed

Barbour, Bernadette; Salameh, Pascale

2009-07-01

The union of individuals with a common ancestor may lead to serious health consequences in their offspring. Consanguinity is high in Middle Eastern communities; it was around 26% in 1988. The objective of this study was to determine the prevalence of consanguinity in Beirut and other Lebanese regions, and its associated factors in different subgroups. The cross-sectional study was performed on a convenience sample of married women in Lebanon. The women were administered a standardized questionnaire in a face-to-face interview by independent enquirers. Among 1556 women, the overall prevalence of consanguineous marriages was 35.5%, and the consanguinity coefficient was 0.020; 968 marriages (62.2%) were not consanguineous, 492 (31.6%) were first cousin, 61 (3.9%) were second cousin and 36 (2.3%) had lower degrees of consanguinity. Beirut suburb dwelling, low education subgroups, women working in the home and non-Christian religion presented the highest rates of consanguinity (p<0.05). Consanguinity is associated with couples' nulliparity and child chronic morbidity. Factors that could affect consanguinity are having consanguineous parents, having a favourable opinion towards consanguinity, choosing a spouse for religious reasons, particularly in Islam, woman having a low education, woman working in the home and women thinking that consanguinity would not lead to serious diseases. Consanguinity is therefore still a prevailing problem in Lebanon. Specific health education, and genetic counselling in particular, are suggested to explain the consequences of consanguinity to the general population and to help couples make informed choices.

Wolcott-Rallison Syndrome Is the Most Common Genetic Cause of Permanent Neonatal Diabetes in Consanguineous Families

PubMed Central

Rubio-Cabezas, Oscar; Patch, Ann-Marie; Minton, Jayne A. L.; Flanagan, Sarah E.; Edghill, Emma L.; Hussain, Khalid; Balafrej, Amina; Deeb, Asma; Buchanan, Charles R.; Jefferson, Ian G.; Mutair, Angham; Hattersley, Andrew T.; Ellard, Sian

2009-01-01

Context and Objective: Mutations in EIF2AK3 cause Wolcott-Rallison syndrome (WRS), a rare recessive disorder characterized by early-onset diabetes, skeletal abnormalities, and liver dysfunction. Although early diagnosis is important for clinical management, genetic testing is generally performed after the full clinical picture develops. We aimed to identify patients with WRS before any other abnormalities apart from diabetes are present and study the overall frequency of WRS among patients with permanent neonatal diabetes. Research Design and Methods: The coding regions of EIF2AK3 were sequenced in 34 probands with infancy-onset diabetes with a clinical phenotype suggestive of WRS (n = 28) or homozygosity at the WRS locus (n = 6). Results: Twenty-five probands (73.5%) were homozygous or compound heterozygous for mutations in EIF2AK3. Twenty of the 26 mutations identified were novel. Whereas a diagnosis of WRS was suspected before genetic testing in 22 probands, three patients with apparently isolated diabetes were diagnosed after identifying a large homozygous region encompassing EIF2AK3. In contrast to nonconsanguineous pedigrees, mutations in EIF2AK3 are the most common known genetic cause of diabetes among patients born to consanguineous parents (24 vs. < 2%). Age at diabetes onset and birth weight might be used to prioritize genetic testing in the latter group. Conclusions: WRS is the most common cause of permanent neonatal diabetes mellitus in consanguineous pedigrees. In addition to testing patients with a definite clinical diagnosis, EIF2AK3 should be tested in patients with isolated neonatal diabetes diagnosed after 3 wk of age from known consanguineous families, isolated populations, or countries in which inbreeding is frequent. PMID:19837917

Consanguinity and reproductive health among Arabs.

PubMed

Tadmouri, Ghazi O; Nair, Pratibha; Obeid, Tasneem; Al Ali, Mahmoud T; Al Khaja, Najib; Hamamy, Hanan A

2009-10-08

Consanguineous marriages have been practiced since the early existence of modern humans. Until now consanguinity is widely practiced in several global communities with variable rates depending on religion, culture, and geography. Arab populations have a long tradition of consanguinity due to socio-cultural factors. Many Arab countries display some of the highest rates of consanguineous marriages in the world, and specifically first cousin marriages which may reach 25-30% of all marriages. In some countries like Qatar, Yemen, and UAE, consanguinity rates are increasing in the current generation. Research among Arabs and worldwide has indicated that consanguinity could have an effect on some reproductive health parameters such as postnatal mortality and rates of congenital malformations. The association of consanguinity with other reproductive health parameters, such as fertility and fetal wastage, is controversial. The main impact of consanguinity, however, is an increase in the rate of homozygotes for autosomal recessive genetic disorders. Worldwide, known dominant disorders are more numerous than known recessive disorders. However, data on genetic disorders in Arab populations as extracted from the Catalogue of Transmission Genetics in Arabs (CTGA) database indicate a relative abundance of recessive disorders in the region that is clearly associated with the practice of consanguinity.

Consanguinity and reproductive health among Arabs

PubMed Central

Tadmouri, Ghazi O; Nair, Pratibha; Obeid, Tasneem; Al Ali, Mahmoud T; Al Khaja, Najib; Hamamy, Hanan A

2009-01-01

Consanguineous marriages have been practiced since the early existence of modern humans. Until now consanguinity is widely practiced in several global communities with variable rates depending on religion, culture, and geography. Arab populations have a long tradition of consanguinity due to socio-cultural factors. Many Arab countries display some of the highest rates of consanguineous marriages in the world, and specifically first cousin marriages which may reach 25-30% of all marriages. In some countries like Qatar, Yemen, and UAE, consanguinity rates are increasing in the current generation. Research among Arabs and worldwide has indicated that consanguinity could have an effect on some reproductive health parameters such as postnatal mortality and rates of congenital malformations. The association of consanguinity with other reproductive health parameters, such as fertility and fetal wastage, is controversial. The main impact of consanguinity, however, is an increase in the rate of homozygotes for autosomal recessive genetic disorders. Worldwide, known dominant disorders are more numerous than known recessive disorders. However, data on genetic disorders in Arab populations as extracted from the Catalogue of Transmission Genetics in Arabs (CTGA) database indicate a relative abundance of recessive disorders in the region that is clearly associated with the practice of consanguinity. PMID:19811666

A missense mutation in the CRBN gene that segregates with intellectual disability and self-mutilating behaviour in a consanguineous Saudi family

PubMed Central

Sheereen, Atia; Alaamery, Manal; Bawazeer, Shahad; Al Yafee, Yusra; Massadeh, Salam; Eyaid, Wafaa

2017-01-01

Background Autosomal-recessive non-syndromic intellectual disability (ARNS-ID) is an aetiologically heterogeneous disorder. Although little is known about the function of human cereblon (CRBN), its relationship to mild cognitive deficits suggests that it is involved in the basic processes of human memory and learning. Objectives We aim to identify the genetic cause of intellectual disability and self-mutilation in a consanguineous Saudi family with five affected members. Methods Clinical whole-exome sequencing was performed on the proband patient, and Sanger sequencing was done to validate and confirm segregation in other family members. Results A missense variant (c. 1171T>C) in the CRBN gene was identified in five individuals with severe intellectual disability (ID) in a consanguineous Saudi family. The homozygous variant was co-segregating in the family with the phenotype of severe ID, seizures and self-mutilating behaviour. The missense mutation (p.C391R) reported here results in the replacement of a conserved cysteine residue by an arginine in the CULT (cereblon domain of unknown activity, binding cellular ligands and thalidomide) domain of CRBN, which contains a zinc-binding site. Conclusions These findings thus contribute to a growing list of ID disorders caused by CRBN mutations, broaden the spectrum of phenotypes attributable to ARNS-ID and provide new insight into genotype–phenotype correlations between CRBN mutations and the aetiology of ARNS-ID. PMID:28143899

Consanguineous marriage in PR China: a study in rural Man (Manchu) communities.

PubMed

Wang, W; Qian, Cong; Bittles, A H

2002-01-01

Although there is a long history of consanguineous marriage in China, information on its prevalence is very limited. The Man (Qing) dynasty ruled China for over 250 years, but no consanguinity studies have been reported on this important population. The objective of the present investigation was to determine the present-day level of consanguineous marriage in the Man community, and to compare the data with existing consanguinity information on other Chinese populations. The study was conducted in a group of 11 rural Man communities in the north-eastern Chinese province of Liaoning. Household-based interviews were conducted by local staff on 513 couples, 418 of whom were Man with another 95 Man-Han inter-ethnic marriages. Basic pedigrees were constructed to determine the biological relationship between each set of spouses. Thirty of the 418 couples were in a consanguineous union, with a mean coefficient of inbreeding alpha = 0.0012. The small population sizes of the study may have contributed to the spatial variation in the patterns of inbreeding. Across generations there was a reduction in consanguineous marriages and an increase in inter-ethnic unions, which paralleled changes in civil marriage regulations.

Novel C8orf37 mutations cause retinitis pigmentosa in consanguineous families of Pakistani origin

PubMed Central

Ravesh, Zeinab; El Asrag, Mohammed E.; Weisschuh, Nicole; McKibbin, Martin; Reuter, Peggy; Watson, Christopher M.; Baumann, Britta; Poulter, James A.; Sajid, Sundus; Panagiotou, Evangelia S.; O’Sullivan, James; Abdelhamed, Zakia; Bonin, Michael; Soltanifar, Mehdi; Black, Graeme C.M.; Din, Muhammad Amin-ud; Toomes, Carmel; Ansar, Muhammad; Inglehearn, Chris F.; Wissinger, Bernd

2015-01-01

Purpose To investigate the molecular basis of retinitis pigmentosa in two consanguineous families of Pakistani origin with multiple affected members. Methods Homozygosity mapping and Sanger sequencing of candidate genes were performed in one family while the other was analyzed with whole exome next-generation sequencing. A minigene splicing assay was used to confirm the splicing defects. Results In family MA48, a novel homozygous nucleotide substitution in C8orf37, c.244–2A>C, that disrupted the consensus splice acceptor site of exon 3 was found. The minigene splicing assay revealed that this mutation activated a cryptic splice site within exon 3, causing a 22 bp deletion in the transcript that is predicted to lead to a frameshift followed by premature protein truncation. In family MA13, a novel homozygous null mutation in C8orf37, c.555G>A, p.W185*, was identified. Both mutations segregated with the disease phenotype as expected in a recessive manner and were absent in 8,244 unrelated individuals of South Asian origin. Conclusions In this report, we describe C8orf37 mutations that cause retinal dystrophy in two families of Pakistani origin, contributing further data on the phenotype and the spectrum of mutations in this form of retinitis pigmentosa. PMID:25802487

Consanguineous marriages in the United Arab Emirates.

PubMed

al-Gazali, L I; Bener, A; Abdulrazzaq, Y M; Micallef, R; al-Khayat, A I; Gaber, T

1997-10-01

This study examines the frequency of consanguineous marriage and the coefficient of inbreeding in the United Arab Emirates (UAE). The study was conducted in Al Ain and Dubai cities between October 1994 and March 1995. A sample of 2033 married UAE females aged 15 years and over participated. The degree of consanguinity between each female and her spouse, and the degree of consanguinity between their parents were recorded. The rate of consanguinity in the present generation was high (50.5%) with a coefficient of inbreeding of 0.0222. The commonest type of consanguineous marriage was between first cousins (26.2%). Double first cousin marriages were common (3.5%) compared to other populations. The consanguinity rate in the UAE has increased from 39% to 50.5% in one generation. The level of consanguinity was higher in Al Ain (54.2%) than in Dubai (40%).

KIN AND NON-KIN MARRIAGES AND FAMILY STRUCTURE IN A RICH TRIBAL SOCIETY.

PubMed

Bakoush, Omran; Bredan, Amin; Denic, Srdjan

2016-11-01

Human consanguinity is often attributed to poverty, lack of education and social insecurity. Nevertheless, kin unions continue to be arranged in socioeconomically transformed societies. This study examined the structure of families and marriages in the rich tribal society of the United Arab Emirates, which has had a high gross domestic product for the last two generations and currently has one of the highest in the world. The respondents were 217 national medical students whose families are proportionally distributed to the population of the country emirates. The rate of parental consanguinity (defined as a union of any two cousins) was 36%. The social status and mean size of consanguineous and non-consanguineous families were not significantly different. In non-consanguineous families, polygamy was more common and the number of half-siblings per family was higher. The extended families were on average 7% larger among non-consanguineous families. In contrast, for the extended families of the participants' grandparents, non-consanguineous families were smaller than their consanguineous counterparts. Participants from consanguineous families indicated that marriage of either a son or daughter was more difficult to arrange than did participants from non-consanguineous families. Though consanguineous parents had their offspring marry consanguineously more often than non-consanguineous parents, the numbers of married offspring in the two groups of families were not different. Consanguineous parents have more difficulty than non-consanguineous parents in finding spouses for themselves and for their offspring, and they arranged kin marriages for their children more often.

Attitude of Saudi Arabian adults towards consanguineous marriage

PubMed Central

Alharbi, Omar A.; Al-Shaia, Walaa A.; Al-Hamam, Abdulaziz A.; Al-Marzoug, Hala M.; Ahmed, Anwar E.; Bagha, Muhammed

2015-01-01

Background: Research on the attitudes of Saudi adults towards consanguinity is scarce. The study aimed to explore the attitudes towards consanguinity and its associations with socio-demographic characteristics in a sample of Saudi adults. Methods: A cross-sectional study was conducted using a self-administered questionnaire. A total of 386 outpatient waiting-area attendees at King Abdul-Aziz Medical City-Riyadh were included. Participants were asked about their socio-demographic characteristics, attitude towards consanguinity and the reasons behind this. Results: The positive attitude towards consanguinity among the study respondents was 48.1% with 95% confidence interval (42.91–53.33%). Social and traditional culture (59.9%) were found to be the predominant reasons for favoring consanguinity in Saudi Arabia. Evidence against a positive attitude towards consanguinity was noted in respondents who received medical information about consanguinity versus those who had not received medical information (42.3% vs. 57%, p-value = 0.008). According to the multivariate logistic model, the odds of a positive attitude towards consanguinity were 2 times higher for males (adjusted odds ratio [aOR]: 2.2; 95% CI: 1.147, 4.290) and 4.1 times higher in respondents in consanguineous marriages (aOR: 4.1; 95% CI: 2.350, 7.156). The odds of a positive attitude towards consanguinity were 50% less in respondents who received health information on consanguinity compared to those who had not received health information about consanguinity (aOR: 0.50; 95% CI: 0.253, 0.863). Conclusion: One in every two Saudi adults favors consanguinity however, Saudi men and women differ in their attitudes towards consanguinity. Receiving health information on consanguinity was associated with a negative attitude towards this practice. PMID:26835408

Mapping autosomal recessive intellectual disability: combined microarray and exome sequencing identifies 26 novel candidate genes in 192 consanguineous families.

PubMed

Harripaul, R; Vasli, N; Mikhailov, A; Rafiq, M A; Mittal, K; Windpassinger, C; Sheikh, T I; Noor, A; Mahmood, H; Downey, S; Johnson, M; Vleuten, K; Bell, L; Ilyas, M; Khan, F S; Khan, V; Moradi, M; Ayaz, M; Naeem, F; Heidari, A; Ahmed, I; Ghadami, S; Agha, Z; Zeinali, S; Qamar, R; Mozhdehipanah, H; John, P; Mir, A; Ansar, M; French, L; Ayub, M; Vincent, J B

2018-04-01

Approximately 1% of the global population is affected by intellectual disability (ID), and the majority receive no molecular diagnosis. Previous studies have indicated high levels of genetic heterogeneity, with estimates of more than 2500 autosomal ID genes, the majority of which are autosomal recessive (AR). Here, we combined microarray genotyping, homozygosity-by-descent (HBD) mapping, copy number variation (CNV) analysis, and whole exome sequencing (WES) to identify disease genes/mutations in 192 multiplex Pakistani and Iranian consanguineous families with non-syndromic ID. We identified definite or candidate mutations (or CNVs) in 51% of families in 72 different genes, including 26 not previously reported for ARID. The new ARID genes include nine with loss-of-function mutations (ABI2, MAPK8, MPDZ, PIDD1, SLAIN1, TBC1D23, TRAPPC6B, UBA7 and USP44), and missense mutations include the first reports of variants in BDNF or TET1 associated with ID. The genes identified also showed overlap with de novo gene sets for other neuropsychiatric disorders. Transcriptional studies showed prominent expression in the prenatal brain. The high yield of AR mutations for ID indicated that this approach has excellent clinical potential and should inform clinical diagnostics, including clinical whole exome and genome sequencing, for populations in which consanguinity is common. As with other AR disorders, the relevance will also apply to outbred populations.

Genetic analysis of fructose-1,6-bisphosphatase (FBPase) deficiency in nine consanguineous Pakistani families.

PubMed

Ijaz, Sadaqat; Zahoor, Muhammad Yasir; Imran, Muhammad; Ramzan, Khushnooda; Bhinder, Munir Ahmad; Shakeel, Hussain; Iqbal, Muhammad; Aslam, Asim; Shehzad, Wasim; Cheema, Huma Arshad; Rehman, Habib

2017-10-26

Fructose-1,6-bisphosphatase (FBPase) deficiency is a rare inherited metabolic disorder characterized by recurrent episodes of hypoglycemia, ketosis and lactic acidosis. FBPase is encoded by FBP1 gene and catalyzes the hydrolysis of fructose-1,6-bisphosphate to fructose-6-phosphate in the last step of gluconeogenesis. We report here FBP1 mutations in nine consanguineous Pakistani families affected with FBPase deficiency. Nine families having one or two individuals affected with FBPase deficiency were enrolled over a period of 3 years. All FBP1 exonic regions including splicing sites were PCR-amplified and sequenced bidirectionally. Familial cosegregation of mutations with disease was confirmed by direct sequencing and PCR-RFLP analysis. Three different FBP1 mutations were identified. Each of two previously reported mutations (c.472C>T (p.Arg158Trp) and c.841G>A (p.Glu281Lys)) was carried by four different families. The ninth family carried a novel 4-bp deletion (c.609_612delAAAA), which is predicted to result in frameshift (p.Lys204Argfs*72) and loss of FBPase function. The novel variant was not detected in any of 120 chromosomes from normal ethnically matched individuals. FBPase deficiency is often fatal in the infancy and early childhood. Early diagnosis and prompt treatment is therefore crucial to preventing early mortality. We recommend the use of c.472C>T and c.841G>A mutations as first choice genetic markers for molecular diagnosis of FBPase deficiency in Pakistan.

A missense mutation in the CRBN gene that segregates with intellectual disability and self-mutilating behaviour in a consanguineous Saudi family.

PubMed

Sheereen, Atia; Alaamery, Manal; Bawazeer, Shahad; Al Yafee, Yusra; Massadeh, Salam; Eyaid, Wafaa

2017-04-01

Autosomal-recessive non-syndromic intellectual disability (ARNS-ID) is an aetiologically heterogeneous disorder. Although little is known about the function of human cereblon (CRBN), its relationship to mild cognitive deficits suggests that it is involved in the basic processes of human memory and learning. We aim to identify the genetic cause of intellectual disability and self-mutilation in a consanguineous Saudi family with five affected members. Clinical whole-exome sequencing was performed on the proband patient, and Sanger sequencing was done to validate and confirm segregation in other family members. A missense variant (c. 1171T>C) in the CRBN gene was identified in five individuals with severe intellectual disability (ID) in a consanguineous Saudi family. The homozygous variant was co-segregating in the family with the phenotype of severe ID, seizures and self-mutilating behaviour. The missense mutation (p.C391R) reported here results in the replacement of a conserved cysteine residue by an arginine in the CULT (cereblon domain of unknown activity, binding cellular ligands and thalidomide) domain of CRBN, which contains a zinc-binding site. These findings thus contribute to a growing list of ID disorders caused by CRBN mutations, broaden the spectrum of phenotypes attributable to ARNS-ID and provide new insight into genotype-phenotype correlations between CRBN mutations and the aetiology of ARNS-ID. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

SYNE1 related cerebellar ataxia presents with variable phenotypes in a consanguineous family from Turkey.

PubMed

Yucesan, E; Ugur Iseri, Sibel A; Bilgic, B; Gormez, Z; Bakir Gungor, B; Sarac, A; Ozdemir, O; Sagiroglu, M; Gurvit, H; Hanagasi, H; Ozbek, U

2017-12-01

SYNE1 related autosomal recessive cerebellar ataxia type 1 (ARCA1) is a late-onset cerebellar ataxia with slow progression originally demonstrated in French-Canadian populations of Quebec, Canada. Nevertheless, recent studies on SYNE1 ataxia have conveyed the condition from a geographically limited pure cerebellar recessive ataxia to a complex multisystem phenotype that is relatively common on the global scale. To determine the underlying genetic cause of the ataxia phenotype in a consanguineous family from Turkey presenting with very slow progressive cerebellar symptoms including dysarthria, dysmetria, and gait ataxia, we performed SNP-based linkage analysis in the family along with whole exome sequencing (WES) in two affected siblings. We identified a homozygous variant in SYNE1 (NM_033071.3: c.13086delC; p.His4362GlnfsX2) in all four affected siblings. This variant presented herein has originally been associated with only pure ataxia in a single case. We thus present segregation and phenotypic manifestations of this variant in four affected family members and further extend the pure ataxia phenotype with upper motor neuron involvement and peripheral neuropathy. Our findings in turn established a precise molecular diagnosis in this family, demonstrating the use of WES combined with linkage analysis in families as a powerful tool for establishing a quick and precise genetic diagnosis of complex neurological phenotypes.

Pathogenic mutations in TULP1 responsible for retinitis pigmentosa identified in consanguineous familial cases

PubMed Central

Ullah, Inayat; Kabir, Firoz; Iqbal, Muhammad; Gottsch, Clare Brooks S.; Naeem, Muhammad Asif; Assir, Muhammad Zaman; Khan, Shaheen N.; Akram, Javed; Riazuddin, Sheikh; Ayyagari, Radha; Hejtmancik, J. Fielding

2016-01-01

Purpose To identify pathogenic mutations responsible for autosomal recessive retinitis pigmentosa (arRP) in consanguineous familial cases. Methods Seven large familial cases with multiple individuals diagnosed with retinitis pigmentosa were included in the study. Affected individuals in these families underwent ophthalmic examinations to document the symptoms and confirm the initial diagnosis. Blood samples were collected from all participating members, and genomic DNA was extracted. An exclusion analysis with microsatellite markers spanning the TULP1 locus on chromosome 6p was performed, and two-point logarithm of odds (LOD) scores were calculated. All coding exons along with the exon–intron boundaries of TULP1 were sequenced bidirectionally. We constructed a single nucleotide polymorphism (SNP) haplotype for the four familial cases harboring the K489R allele and estimated the likelihood of a founder effect. Results The ophthalmic examinations of the affected individuals in these familial cases were suggestive of RP. Exclusion analyses confirmed linkage to chromosome 6p harboring TULP1 with positive two-point LOD scores. Subsequent Sanger sequencing identified the single base pair substitution in exon14, c.1466A>G (p.K489R), in four families. Additionally, we identified a two-base deletion in exon 4, c.286_287delGA (p.E96Gfs77*); a homozygous splice site variant in intron 14, c.1495+4A>C; and a novel missense variation in exon 15, c.1561C>T (p.P521S). All mutations segregated with the disease phenotype in the respective families and were absent in ethnically matched control chromosomes. Haplotype analysis suggested (p<10−6) that affected individuals inherited the causal mutation from a common ancestor. Conclusions Pathogenic mutations in TULP1 are responsible for the RP phenotype in seven familial cases with a common ancestral mutation responsible for the disease phenotype in four of the seven families. PMID:27440997

Prevalence of consanguineous marriages among Iranian Georgians.

PubMed

Rafiee, Laleh; Saadat, Mostafa

2011-01-01

Consanguineous marriage--marriage between relatives--has received a great deal of attention as a potential risk factor for many adverse health outcomes. The present cross-sectional study was done in order to illustrate the prevalence and types of consanguineous marriages among Iranian Georgians living in Frydoonshahr (Isfahan province, central Iran). Data on consanguineous marriages were collected using a simple questionnaire. The total number of couples in this study was 646. Consanguineous marriage was classified by the degree of relationship between couples. First cousin marriages (14.2%) were the most common type of consanguineous marriages, followed by second cousin (7.0%), beyond second cousin (1.5%) and first cousin once removed (0.6%). The mean inbreeding coefficient (α) was calculated as 0.0104 for the population. The present study shows that the study population, as other Iranian populations, has a high level of consanguinity.

Consanguineous marriages in Afghanistan.

PubMed

Saify, Khyber; Saadat, Mostafa

2012-01-01

The present cross-sectional study was done in order to illustrate the prevalence and types of consanguineous marriages among Afghanistan populations. Data on types of marriages were collected using a simple questionnaire. The total number of couples in the study was 7140 from the following provinces: Badakhshan, Baghlan, Balkh, Bamyan, Kabul, Kunduz, Samangan and Takhar. Consanguineous marriages were classified by the degree of relationship between couples: double first cousins, first cousins, first cousins once removed, second cousins and beyond second cousins. The coefficient of inbreeding (F) was calculated for each couple and the mean coefficient of inbreeding (α) estimated for each population. The proportion of consanguineous marriages in the country was 46.2%, ranging from 38.2% in Kabul province to 51.2% in Bamyan province. The equivalent mean inbreeding coefficient (α) was 0.0277, and ranged from 0.0221 to 0.0293 in these two regions. There were significant differences between provinces for frequencies of different types of marriages (p<0.001). First cousin marriages (27.8%) were the most common type of consanguineous marriages, followed by double first cousin (6.9%), second cousin (5.8%), beyond second cousin (3.9%) and first cousin once removed (1.8%). There were significant differences between ethnic groups for the types of marriages (χ2=177.6, df=25, p<0.001). Tajiks (Soni) and Turkmens (also Pashtuns) showed the lowest (α=0.0250) and highest (α=0.0297) mean inbreeding coefficients, respectively, among the ethnic groups in Afghanistan. The study shows that Afghanistan's populations, like other Islamic populations, have a high level of consanguinity.

Relationship between birth order of spouses with different degrees of consanguineous relationship.

PubMed

Reddy, B M; Malhotra, K C

1991-08-01

The relationship between birth order of spouses with different degrees of consanguinity is examined in a sample of 1826 couples belonging to the endogamous Vadde Fisherfolk of Kolleru Lake, Andhra Pradesh, India. We attempt to explain the wide variation in the frequency of different kinds of consanguineous marriages through the age-sex structure of the population in general and especially of the related families. This structure may also be manifested in the association between the birth orders of spouses. A highly significant and large correlation between the birth orders of spouses in uncle-niece marriages and a gradual decrease in the correlation with increase in remoteness of the relationship between the spouses were observed. Given the distribution of age differences between the spouses and assuming a standard age-sex structure, it seems possible to estimate the optimum frequency with which at least close consanguineous marriages occur in any particular population.

Impact of 226C>T MSH2 gene mutation on cancer phenotypes in two HNPCC-associated highly-consanguineous families from Kuwait: emphasis on premarital genetic testing.

PubMed

Marafie, Makia J; Al-Awadi, Sadiqa; Al-Mosawi, Fatemah; Elshafey, Alaa; Al-Ali, Waleed; Al-Mulla, Fahd

2009-01-01

Lynch syndrome or hereditary nonpolyposis colorectal cancer (HNPCC) is one of the commonest cancer susceptibility syndromes. It is characterized by early onset colon cancer and a variety of extracolonic tumours. Germline mutations in the DNA mismatch repair genes (MLH1, MSH2, MSH6, PMS1, and PMS2) are responsible for this disorder. Identifying an affected individual depends on the tumour histopathology, family history that fulfils the Amsterdam and/or Bethesda criteria, tumour immunohistochemistry, microsatellite instability, and finally molecular analysis of an affected member. It is a laborious, time consuming and expensive procedure, which needs the effort of a multi-disciplinary team. However, once the diagnosis is established and germline defect is identified, other high risk pre-symptomatic carriers could be offered intensive surveillance and management as a preventive measure against cancer development. Here, we present two large highly consanguineous HNPCC-families from Kuwait in whom a founder MSH2 mutation was identified. The relationship between this mutation and cancer expressivity in two large consanguineous families harbouring other genetic defects is discussed. Moreover, we shed light on the challenges pertaining to diagnosis, screening, premarital counselling of couples and prenatal diagnosis of offspring with biallelic MSH2 gene mutation.

Prevalence of consanguineous marriages in Syria.

PubMed

Othman, Hasan; Saadat, Mostafa

2009-09-01

Consanguineous marriage is the union of individuals having at least one common ancestor. The present cross-sectional study was done in order to illustrate the prevalence and types of consanguineous marriages in the Syrian Arab Republic. Data on consanguineous marriages were collected using a simple questionnaire. The total number of couples in this study was 67,958 (urban areas: 36,574 couples; rural areas: 31,384 couples) from the following provinces: Damascus, Hamah, Tartous, Latakia, Al Raqa, Homs, Edlep and Aleppo. In each province urban and rural areas were surveyed. Consanguineous marriage was classified by the degree of relationship between couples: double first cousins (F=1/8), first cousins (F=1/16), second cousins (F=1/64) and beyond second cousins (F<1/64). The coefficient of inbreeding (F) was calculated for each couple and the mean coefficient of inbreeding (alpha) estimated for the population of each province, stratified by rural and urban areas. The results showed that the overall frequency of consanguinity was 30.3% in urban and 39.8% in rural areas. Total rate of consanguinity was found to be 35.4%. The equivalent mean inbreeding coefficient (alpha) was 0.0203 and 0.0265 in urban and rural areas, respectively. The mean proportion of consanguineous marriages ranged from 67.5% in Al Raqa province to 22.1% in Latakia province. The alpha-value ranged from 0.0358 to 0.0127 in these two provinces, respectively. The western and north-western provinces (including Tartous, Lattakia and Edlep) recorded lower levels of inbreeding than the central, northern and southern provinces. The overall alpha-value was estimated to be about 0.0236 for the studied populations. First cousin marriages (with 20.9%) were the most common type of consanguineous marriages, followed by double first cousin (with 7.8%) and second cousin marriages (with 3.3%), and beyond second cousin was the least common type.

Consanguinity and Its Sociodemographic Differentials in Bhimber District, Azad Jammu and Kashmir, Pakistan

PubMed Central

Jabeen, Nazish

2014-01-01

ABSTRACT Kashmiri population in the northeast of Pakistan has strong historical, cultural and linguistic affinities with the neighbouring populations of upper Punjab and Potohar region of Pakistan. However, the study of consanguineous unions, which are customarily practised in many populations of Pakistan, revealed marked differences between the Kashmiris and other populations of northern Pakistan with respect to the distribution of marriage types and inbreeding coefficient (F). The current descriptive epidemiological study carried out in Bhimber district of Mirpur division, Azad Jammu and Kashmir, Pakistan, demonstrated that consanguineous marriages were 62% of the total marriages (F=0.0348). First-cousin unions were the predominant type of marriages and constituted 50.13% of total marital unions. The estimates of inbreeding coefficient were higher in the literate subjects, and consanguinity was witnessed to be rising with increasing literacy level. Additionally, consanguinity was observed to be associated with ethnicity, family structure, language, and marriage arrangements. Based upon these data, a distinct sociobiological structure, with increased stratification and higher genomic homozygosity, is expected for this Kashmiri population. In this communication, we present detailed distribution of the types of marital unions and the incidences of consanguinity and inbreeding coefficient (F) across various sociodemographic strata of Bhimber/Mirpuri population. The results of this study would have implication not only for other endogamous populations of Pakistan but also for the sizeable Kashmiri community immigrated to Europe. PMID:25076667

A novel DFNB31 mutation associated with Usher type 2 syndrome showing variable degrees of auditory loss in a consanguineous Portuguese family.

PubMed

Audo, Isabelle; Bujakowska, Kinga; Mohand-Saïd, Saddek; Tronche, Sophie; Lancelot, Marie-Elise; Antonio, Aline; Germain, Aurore; Lonjou, Christine; Carpentier, Wassila; Sahel, José-Alain; Bhattacharya, Shomi; Zeitz, Christina

2011-01-01

To identify the genetic defect of a consanguineous Portuguese family with rod-cone dystrophy and varying degrees of decreased audition. A detailed ophthalmic and auditory examination was performed on a Portuguese patient with severe autosomal recessive rod-cone dystrophy. Known genetic defects were excluded by performing autosomal recessive retinitis pigmentosa (arRP) genotyping microarray analysis and by Sanger sequencing of the coding exons and flanking intronic regions of eyes shut homolog-drosophila (EYS) and chromosome 2 open reading frame 71 (C2orf71). Subsequently, genome-wide homozygosity mapping was performed in DNA samples from available family members using a 700K single nucleotide polymorphism (SNP) microarray. Candidate genes present in the significantly large homozygous regions were screened for mutations using Sanger sequencing. The largest homozygous region (~11 Mb) in the affected family members was mapped to chromosome 9, which harbors deafness, autosomal recessive 31 (DFNB31; a gene previously associated with Usher syndrome). Mutation analysis of DFNB31 in the index patient identified a novel one-base-pair deletion (c.737delC), which is predicted to lead to a truncated protein (p.Pro246HisfsX13) and co-segregated with the disease in the family. Ophthalmic examination of the index patient and the affected siblings showed severe rod-cone dystrophy. Pure tone audiometry revealed a moderate hearing loss in the index patient, whereas the affected siblings were reported with more profound and early onset hearing impairment. We report a novel truncating mutation in DFNB31 associated with severe rod-cone dystrophy and varying degrees of hearing impairment in a consanguineous family of Portuguese origin. This is the second report of DFNB31 implication in Usher type 2.

Consanguineous marriages in the province of Antalya, Turkey.

PubMed

Alper, O M; Erengin, H; Manguoğlu, A E; Bilgen, T; Cetin, Z; Dedeoğlu, N; Lüleci, G

2004-01-01

To assess the trends in the frequency and the medical effects of consanguinity in the south coast of Turkish population using local and national data in the last 11 years. This cross-sectional study was carried out in Manavgat province, which is a major tourism center on the Mediterranean coast of Turkey. The authors studied consanguineous marriages in rural and urban population in the Mediterranean coast, Manavgat province, Turkey, via a 1500 random survey sample of married couples. There has been a significant increase in the incidence of consanguineous marriages in rural areas (40.7%) since 1989 in the southern population of Turkey. The results showed that the most frequent type of marriage was between the first cousins. It is found that there is no statistically significant difference between the consanguineous and non-consanguineous marriages in the different age groups. The results were discussed on the basis of educational status, reasons for having consanguineous marriages and the general medical effects as well as with the relation of congenital malformations. The custom of consanguineous unions in the Mediterranean population of Turkey is still extremely high, and preventive measures should be done to decrease its frequency and associated complications.

Variable pathogenicity of exon 43del (FAA) in four Fanconi anaemia patients within a consanguineous family.

PubMed

Koc, A; Pronk, J C; Alikasifoglu, M; Joenje, H; Altay, C

1999-01-01

Four Fanconi anaemia group A (FAA) patients within two related consanguineous families are presented: the propositus (male, 13 years, transplanted at age 10), and his three cousins (one male, 8 years, and two female newborns). Assignment of the patients to FAA was based on the functional complementation analysis by somatic cell hybridization and confirmed by mutation screening showing a homozygous deletion of exon 43 (4267-4404del) in the FAA gene to be present in all four patients. The newborn patients had been diagnosed prenatally by DNA analysis. In spite of identical molecular pathology and close familial relationship the clinical phenotypes of the four patients were not concordant. Discordant symptoms included birthweight, pigmentation abnormalities, skeletal, renal and genital abnormalities, whereas microcephaly and possibly the haematological course were concordant. Differences in environmental conditions and/or genetic make-up along with chance effects during development may explain discordant phenotypes despite identical molecular pathology in these patients. However, our results do not rule out the possibility that the exon 43del mutation may have prognostic value for the haematological course of the disease.

Biosocial correlates and spatial distribution of consanguinity in South America.

PubMed

Bronberg, Ruben; Gili, Juan; Gimenez, Lucas; Dipierri, Jose; Lopez Camelo, Jorge

2016-05-01

To analyze potential biosocial factors in consanguineous unions according to the level of consanguinity and its spatial distribution in South America. The data used came from the Latin American Collaborative Study of Congenital Malformations. Information on 126,213 nonmalformed newborns out of 6,014,749 births was used. This information was collected between 1967 and 2011 at 204 hospitals in 116 cities in 10 South American countries. The spatial scan statistic was performed under a model of nonhierarchical k-means segmentation, based on statistically significant clusters, areas with levels of high, medium, and low consanguinity were determined. Consanguinity in South America is heterogeneously distributed, with two groups of high consanguinity, in northwestern Venezuela and southeast of Brazil, and two clusters of low consanguinity located in the south of the continent, mainly Argentina. The socio-demographic factors associated with consanguinity influence the population structure in areas of high consanguinity. This study demonstrates that consanguinity in the South American continent is strongly associated with a greater magnitude of poverty in the area of high consanguinity. Am. J. Hum. Biol. 28:405-411, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

A Common Ancestral Mutation in CRYBB3 Identified in Multiple Consanguineous Families with Congenital Cataracts

PubMed Central

Irum, Bushra; Khan, Arif O.; Wang, Qiwei; Li, David; Khan, Asma A.; Husnain, Tayyab; Akram, Javed; Riazuddin, Sheikh

2016-01-01

Purpose This study was performed to investigate the genetic determinants of autosomal recessive congenital cataracts in large consanguineous families. Methods Affected individuals underwent a detailed ophthalmological examination and slit-lamp photographs of the cataractous lenses were obtained. An aliquot of blood was collected from all participating family members and genomic DNA was extracted from white blood cells. Initially, a genome-wide scan was performed with genomic DNAs of family PKCC025 followed by exclusion analysis of our familial cohort of congenital cataracts. Protein-coding exons of CRYBB1, CRYBB2, CRYBB3, and CRYBA4 were sequenced bidirectionally. A haplotype was constructed with SNPs flanking the causal mutation for affected individuals in all four families, while the probability that the four familial cases have a common founder was estimated using EM and CHM-based algorithms. The expression of Crybb3 in the developing murine lens was investigated using TaqMan assays. Results The clinical and ophthalmological examinations suggested that all affected individuals had nuclear cataracts. Genome-wide linkage analysis localized the causal phenotype in family PKCC025 to chromosome 22q with statistically significant two-point logarithm of odds (LOD) scores. Subsequently, we localized three additional families, PKCC063, PKCC131, and PKCC168 to chromosome 22q. Bidirectional Sanger sequencing identified a missense variation: c.493G>C (p.Gly165Arg) in CRYBB3 that segregated with the disease phenotype in all four familial cases. This variation was not found in ethnically matched control chromosomes, the NHLBI exome variant server, or the 1000 Genomes or dbSNP databases. Interestingly, all four families harbor a unique disease haplotype that strongly suggests a common founder of the causal mutation (p<1.64E-10). We observed expression of Crybb3 in the mouse lens as early as embryonic day 15 (E15), and expression remained relatively steady throughout

Autosomal Recessive Mental Retardation, Deafness, Ankylosis, and Mild Hypophosphatemia Associated with a Novel ANKH Mutation in a Consanguineous Family

PubMed Central

Morava, Eva; Kühnisch, Jirko; Drijvers, Jefte M.; Robben, Joris H.; Cremers, Cor; van Setten, Petra; Branten, Amanda; Stumpp, Sabine; de Jong, Alphons; Voesenek, Krysta; Vermeer, Sascha; Heister, Angelien; Claahsen-van der Grinten, Hedi L.; O'Neill, Charles W.; Willemsen, Michèl A.; Lefeber, Dirk; Deen, Peter M. T.; Kornak, Uwe; Kremer, Hannie; Wevers, Ron A.

2011-01-01

Context: Mutations in ANKH cause the highly divergent conditions familial chondrocalcinosis and craniometaphyseal dysplasia. The gene product ANK is supposed to regulate tissue mineralization by transporting pyrophosphate to the extracellular space. Objective: We evaluated several family members of a large consanguineous family with mental retardation, deafness, and ankylosis. We compared their skeletal, metabolic, and serological parameters to that of the autosomal recessive progressive ankylosis (ank) mouse mutant, caused by a loss-of-function mutation in the murine ortholog Ank. Participants: The studied patients had painful small joint soft-tissue calcifications, progressive spondylarthropathy, osteopenia, mild hypophosphatemia, mixed hearing loss, and mental retardation. Results: After mapping the disease gene to 5p15, we identified the novel homozygous ANK missense mutation L244S in all patients. Although L244 is a highly conserved amino acid, the mutated ANK protein was detected at normal levels at the plasma membrane in primary patient fibroblasts. The phenotype was highly congruent with the autosomal recessive progressive ankylosis (ank) mouse mutant. This indicates a loss-of-function effect of the L244S mutation despite normal ANK protein expression. Interestingly, our analyses revealed that the primary step of joint degeneration is fibrosis and mineralization of articular soft tissues. Moreover, heterozygous carriers of the L244S mutation showed mild osteoarthritis without metabolic alterations, pathological calcifications, or central nervous system involvement. Conclusion: Beyond the description of the first human progressive ankylosis phenotype, our results indicate that ANK influences articular soft tissues commonly involved in degenerative joint disorders. Furthermore, this human disorder provides the first direct evidence for a role of ANK in the central nervous system. PMID:20943778

Autosomal recessive mental retardation, deafness, ankylosis, and mild hypophosphatemia associated with a novel ANKH mutation in a consanguineous family.

PubMed

Morava, Eva; Kühnisch, Jirko; Drijvers, Jefte M; Robben, Joris H; Cremers, Cor; van Setten, Petra; Branten, Amanda; Stumpp, Sabine; de Jong, Alphons; Voesenek, Krysta; Vermeer, Sascha; Heister, Angelien; Claahsen-van der Grinten, Hedi L; O'Neill, Charles W; Willemsen, Michèl A; Lefeber, Dirk; Deen, Peter M T; Kornak, Uwe; Kremer, Hannie; Wevers, Ron A

2011-01-01

Mutations in ANKH cause the highly divergent conditions familial chondrocalcinosis and craniometaphyseal dysplasia. The gene product ANK is supposed to regulate tissue mineralization by transporting pyrophosphate to the extracellular space. We evaluated several family members of a large consanguineous family with mental retardation, deafness, and ankylosis. We compared their skeletal, metabolic, and serological parameters to that of the autosomal recessive progressive ankylosis (ank) mouse mutant, caused by a loss-of-function mutation in the murine ortholog Ank. The studied patients had painful small joint soft-tissue calcifications, progressive spondylarthropathy, osteopenia, mild hypophosphatemia, mixed hearing loss, and mental retardation. After mapping the disease gene to 5p15, we identified the novel homozygous ANK missense mutation L244S in all patients. Although L244 is a highly conserved amino acid, the mutated ANK protein was detected at normal levels at the plasma membrane in primary patient fibroblasts. The phenotype was highly congruent with the autosomal recessive progressive ankylosis (ank) mouse mutant. This indicates a loss-of-function effect of the L244S mutation despite normal ANK protein expression. Interestingly, our analyses revealed that the primary step of joint degeneration is fibrosis and mineralization of articular soft tissues. Moreover, heterozygous carriers of the L244S mutation showed mild osteoarthritis without metabolic alterations, pathological calcifications, or central nervous system involvement. Beyond the description of the first human progressive ankylosis phenotype, our results indicate that ANK influences articular soft tissues commonly involved in degenerative joint disorders. Furthermore, this human disorder provides the first direct evidence for a role of ANK in the central nervous system.

Race, consanguinity and social features in Birmingham babies: a basis for prospective study.

PubMed Central

Bundey, S; Alam, H; Kaur, A; Mir, S; Lancashire, R J

1990-01-01

STUDY OBJECTIVE--The aim of the study was to investigate the influence of consanguinity on children's health. DESIGN--The study is a prospective survey from birth to five years of a cohort of babies born in a multiracial community. This report details the initial findings on consanguinity. SETTING--Participating families live predominantly in three health districts of Birmingham, and were recruited in three local maternity hospitals. PARTICIPANTS--Babies of 2432 European mothers, 509 Afro-Caribbean mothers, 625 Indian mothers, 956 Pakistani mothers, and 216 Bangladeshi mothers have been enrolled in the study. Eighty mothers refused to participate. MEASUREMENTS AND RESULTS--Sociodemographic information was obtained using a structured questionnaire administered at interview. Interview data were supplemented with obstetric information from the medical records. The highest prevalence of parental consanguinity was in Pakistani Muslims (69%), whereas in Muslims from other countries it was 23%, and it was less than 1% in non-Muslims. In the majority of consanguineous Muslim pedigrees the degree of inbreeding was greater than that for first cousin parents. CONCLUSIONS--This prospective study will allow an assessment to be made about any ill health in childhood arising from parental consanguinity, about whether screening programmes are indicated for particular autosomal recessive diseases, and about whether premarital health education might be beneficial. The study has also documented parental ages in different races and this, together with the levels of parental consanguinity in all races, will be useful in genetic methods for assessing the frequency of recessive genes, the possibility of genetic heterogeneity, and whether or not parental age effect exists for new mutations of specific genetic disorders. PMID:2370500

Impact of consanguineous marriages and degrees of inbreeding on fertility, child mortality, secondary sex ratio, selection intensity, and genetic load: a cross-sectional study from Northern India.

PubMed

Fareed, Mohd; Kaisar Ahmad, Mir; Azeem Anwar, Malik; Afzal, Mohammad

2017-01-01

The aim of our study was to understand the relationship between consanguineous marriages and reproductive outcomes. A total of 999 families were recruited from five Muslim populations of Jammu region. Family pedigrees were drawn to access the family history and inbreeding status in terms of coefficient of inbreeding (F). Fertility, mortality, secondary sex ratio, selection intensity, and lethal equivalents were measured using standard methods. The significant differences for gross fertility was found to be higher among inbred groups as compared to the unrelated families (P < 0.05) and higher mortality rates were observed among consanguineous families of all populations in comparison with the non-consanguineous family groups. Moreover, the prenatal and postnatal child mortality rates (i.e., U5MR and U18MR) have presented a persuasive increase with an upsurge in the homozygosity level. The mortality rate was found to be maximum among families with the highest value of coefficient of inbreeding (F). The selection intensity (SI) also showed inflations among families with respect to their increasing inbreeding coefficients. The greater values of lethal equivalents per gamete (LEs/gamete) were observed for autosomal inheritance in comparison with sex-linked inheritance. Our conclusive assessment brings out the deleterious consequence of consanguineous marriages on reproductive outcomes.

The prevalence of isolated growth hormone deficiency among children of short stature in Jordan and its relationship with consanguinity.

PubMed

Zayed, Ayman A; Mustafa Ali, Moaath K; Al-Ani, Mohammad A; Momani, Munther S; Yousef, Al-Motassem F

2014-12-01

The prevalence of isolated growth hormone deficiency (IGHD) among short-statured children in Jordan, where consanguineous marriage (CM) is common, is unknown. No studies have investigated the relationship between degrees of consanguinity and IGHD. This study aimed to determine the prevalence of IGHD among short-statured children referred to a university hospital in Jordan and its relationship with different degrees of consanguinity. We conducted a 24-month cross-sectional observational trial at an outpatient tertiary care center in Amman, Jordan. We obtained detailed family histories, medical evaluations and laboratory tests for 94 short-statured children (50 boys and 44 girls aged 6-16 years). Complete and partial GHD were defined as peak GH responses of 5 and 7 μg/l (15 and 21 mIU/l) [IRMA/DiaSorin®], respectively, in both exercise and insulin tolerance tests. GHD was diagnosed in 69·1% of the short children, including 86% (43/50) of the children of consanguineous parents (83·3%, 93·8% and 81·8% of children of first cousins, first cousins once removed and second cousins, respectively) and 50% (20/44) of the children of nonconsanguineous parents (P = 0·039, 0·002 and 0·013, respectively). However, there was no statistically significant difference in the prevalence of small pituitary MRI between GH-deficient children of consanguineous parents and those of nonconsanguineous parents (28·6% vs 13·6%, P = 0·3). The prevalence of IGHD among referred short children in Jordan was exceptionally high and significantly higher in the children of CM. In countries where CM is common, preconception counselling and rigorous surveillance for GHD in short children may be indicated. © 2014 John Wiley & Sons Ltd.

Consanguinity and other marriage market effects of a wealth shock in Bangladesh.

PubMed

Mobarak, Ahmed Mushfiq; Kuhn, Randall; Peters, Christina

2013-10-01

This paper uses a wealth shock from the construction of a flood protection embankment in rural Bangladesh coupled with data on the universe of all 52,000 marriage decisions between 1982 and 1996 to examine changes in marital prospects for households protected by the embankment relative to unprotected households living on the other side of the river. We use difference-in-difference specifications to document that brides from protected households commanded larger dowries, married wealthier households, and became less likely to marry biological relatives. Financial liquidity-constrained households appear to use within-family marriage (in which one can promise ex-post payments) as a form of credit to meet up-front dowry demands, but the resultant wealth shock for households protected by the embankment relaxed this need to marry consanguineously. Our results shed light on the socioeconomic roots of consanguinity, which carries health risks for offspring but can also carry substantial benefits for the families involved.

Consanguineous marriages in the genetic counseling centers of Isfahan and the ethical issues of clinical consultations.

PubMed

Nouri, Narges; Nouri, Nayereh; Tirgar, Samane; Soleimani, Elham; Yazdani, Vida; Zahedi, Farzaneh; Larijani, Bagher

2017-01-01

Consanguineous marriage, which is common in many regions in the world, has absorbed much attention as a causative factor in raising the incidence of genetic diseases. The adverse effects may be attributed to the expression of the genes received from common ancestors and mortality and morbidity of the offspring. Iran has a high rate of consanguineous marriages. In recent years genetic counseling has come to be considered in health care services. This cross-sectional study was conducted in order to determine the prevalence and types of consanguineous marriages in the genetic clinics in Isfahan. We aimed to define the different types of marriages, specific categories of genetic disorders associated with consanguineous marriages, and mode of inheritance in the family tree. We also narratively reviewed the ethical aspects of the issue. The data were collected using a simple questionnaire. A total number of 1535 couples from urban and rural areas formed the study population. The marriages were classified according to the degree of the relationship between couples, including: double cousin, first cousin, first cousin once removed, second cousin and beyond second cousin. The SPSS software version 16 was used for data analysis. Data obtained through genetic counseling offered during a 5-year period revealed that 74.3% had consanguineous relationships, 62.3% were first cousins, 1% were double cousins and 7.8% were second cousins. In addition, 76% of the couples had at least one genetic disease in their family tree. Related ethical issues were also considered in this study, including autonomy and informed decision making, benefit and harm assessment, confidentiality, ethics in research, justice in access to counseling services, financial problems ethics, and the intellectual property of scientific success.

Exome sequencing of Pakistani consanguineous families identifies 30 novel candidate genes for recessive intellectual disability

PubMed Central

Riazuddin, S; Hussain, M; Razzaq, A; Iqbal, Z; Shahzad, M; Polla, D L; Song, Y; van Beusekom, E; Khan, A A; Tomas-Roca, L; Rashid, M; Zahoor, M Y; Wissink-Lindhout, W M; Basra, M A R; Ansar, M; Agha, Z; van Heeswijk, K; Rasheed, F; Van de Vorst, M; Veltman, J A; Gilissen, C; Akram, J; Kleefstra, T; Assir, M Z; Grozeva, D; Carss, K; Raymond, F L; O'Connor, T D; Riazuddin, S A; Khan, S N; Ahmed, Z M; de Brouwer, A P M; van Bokhoven, H; Riazuddin, S

2017-01-01

Intellectual disability (ID) is a clinically and genetically heterogeneous disorder, affecting 1–3% of the general population. Although research into the genetic causes of ID has recently gained momentum, identification of pathogenic mutations that cause autosomal recessive ID (ARID) has lagged behind, predominantly due to non-availability of sizeable families. Here we present the results of exome sequencing in 121 large consanguineous Pakistani ID families. In 60 families, we identified homozygous or compound heterozygous DNA variants in a single gene, 30 affecting reported ID genes and 30 affecting novel candidate ID genes. Potential pathogenicity of these alleles was supported by co-segregation with the phenotype, low frequency in control populations and the application of stringent bioinformatics analyses. In another eight families segregation of multiple pathogenic variants was observed, affecting 19 genes that were either known or are novel candidates for ID. Transcriptome profiles of normal human brain tissues showed that the novel candidate ID genes formed a network significantly enriched for transcriptional co-expression (P<0.0001) in the frontal cortex during fetal development and in the temporal–parietal and sub-cortex during infancy through adulthood. In addition, proteins encoded by 12 novel ID genes directly interact with previously reported ID proteins in six known pathways essential for cognitive function (P<0.0001). These results suggest that disruptions of temporal parietal and sub-cortical neurogenesis during infancy are critical to the pathophysiology of ID. These findings further expand the existing repertoire of genes involved in ARID, and provide new insights into the molecular mechanisms and the transcriptome map of ID. PMID:27457812

Exome sequencing of Pakistani consanguineous families identifies 30 novel candidate genes for recessive intellectual disability.

PubMed

Riazuddin, S; Hussain, M; Razzaq, A; Iqbal, Z; Shahzad, M; Polla, D L; Song, Y; van Beusekom, E; Khan, A A; Tomas-Roca, L; Rashid, M; Zahoor, M Y; Wissink-Lindhout, W M; Basra, M A R; Ansar, M; Agha, Z; van Heeswijk, K; Rasheed, F; Van de Vorst, M; Veltman, J A; Gilissen, C; Akram, J; Kleefstra, T; Assir, M Z; Grozeva, D; Carss, K; Raymond, F L; O'Connor, T D; Riazuddin, S A; Khan, S N; Ahmed, Z M; de Brouwer, A P M; van Bokhoven, H; Riazuddin, S

2017-11-01

Intellectual disability (ID) is a clinically and genetically heterogeneous disorder, affecting 1-3% of the general population. Although research into the genetic causes of ID has recently gained momentum, identification of pathogenic mutations that cause autosomal recessive ID (ARID) has lagged behind, predominantly due to non-availability of sizeable families. Here we present the results of exome sequencing in 121 large consanguineous Pakistani ID families. In 60 families, we identified homozygous or compound heterozygous DNA variants in a single gene, 30 affecting reported ID genes and 30 affecting novel candidate ID genes. Potential pathogenicity of these alleles was supported by co-segregation with the phenotype, low frequency in control populations and the application of stringent bioinformatics analyses. In another eight families segregation of multiple pathogenic variants was observed, affecting 19 genes that were either known or are novel candidates for ID. Transcriptome profiles of normal human brain tissues showed that the novel candidate ID genes formed a network significantly enriched for transcriptional co-expression (P<0.0001) in the frontal cortex during fetal development and in the temporal-parietal and sub-cortex during infancy through adulthood. In addition, proteins encoded by 12 novel ID genes directly interact with previously reported ID proteins in six known pathways essential for cognitive function (P<0.0001). These results suggest that disruptions of temporal parietal and sub-cortical neurogenesis during infancy are critical to the pathophysiology of ID. These findings further expand the existing repertoire of genes involved in ARID, and provide new insights into the molecular mechanisms and the transcriptome map of ID.

Consanguinity and spousal concordance in Kuwait.

PubMed

al-Kandari, Y; Crews, D E; Poirier, F E

2002-12-01

Consanguineous marriage is favored in Kuwait. This research focuses on the relationship of physical and cultural traits to marriage types in Kuwait and examines concordance as a function of consanguinity and marriage duration. In a nonrandom opportunistic sample of 242 couples anthropometric and blood pressure data have been collected as well as data on acculturation, religiosity, Farsi proficiency, level of education, occupation, and attitudes regarding fertility. Significant concordances occur in cultural characteristics among couples in all three types of marriages with respect to the degree of religiosity, acculturation, language similarity, education, and occupation. Non-consanguineous spouses have the highest concordance in educational level, occupation, and degree of acculturation, but the lowest for religiosity and Farsi proficiency. Nonkin marriages seem to be based on personal preferences. In the wider potential nonkin marriage pool spouses show more concordance in stature and education indicating the positive assortative mating for those traits. Non-consanguineous spouses show a significant association for triceps and subscapular skinfold thicknesses hip and waist circumferences, and body fat distribution. Unrelated spouses exhibit more concordance for physical traits than do related spouses. There is a significant correlation between spouses in first and double cousin marriages as well as in spouses in second and less than second cousin unions for systolic and diastolic blood pressure, while non-consanguineous spouses show a significant association in diastolic blood pressure only.

Genetic Diagnosis in Consanguineous Families With Kidney Disease by Homozygosity Mapping Coupled With Whole-Exome Sequencing

PubMed Central

Al-Romaih, Khaldoun I.; Genovese, Giulio; Al-Mojalli, Hamad; Al-Othman, Saleh; Al-Manea, Hadeel; Al-Suleiman, Mohammed; Al-Jondubi, Mohammed; Atallah, Nourah; Al-Rodhyan, Maha; Weins, Astrid; Pollak, Martin R.; Adra, Chaker N.

2011-01-01

Background Accurate diagnosis of the primary cause of an individual’s kidney disease can be essential for proper management. Some kidney diseases have overlapping histopathological features despite being caused by defects in different genes. In this report we describe two consanguineous Saudi Arabian families in which individuals presented with kidney failure and mixed clinical and histological features initially thought consistent with focal segmental glomerulosclerosis. Study Design Case series. Setting and participants We studied members of two apparently unrelated families from Saudi Arabia with kidney disease. Measurements Whole-genome single-nucleotide polymorphism analysis followed by targeted isolation and sequencing of exons using genomic DNA samples from affected members of these families, followed by additional focused genotyping and sequence analysis. Results The two apparently unrelated families shared a region of homozygosity on chromosome 2q13. Exome sequence from the affected individuals lacked any sequence reads from the NPHP1 gene, which is located within this homozygous region. Additional PCR based genotyping confirmed that affected individuals had NPHP1 deletions, rather than defects in a known FSGS-associated gene. Limitations The methods used here may not result in a clear genetic diagnosis in many cases of apparent familial kidney disease. Conclusions This analysis demonstrates the power of new high-throughput genotyping and sequencing technologies to aid in the rapid genetic diagnosis of individuals with an inherited form of kidney disease. We believe it is likely that such tools may become useful clinical genetic tools and alter the manner in which diagnoses are made in nephrology. PMID:21658830

Modernization and Consanguineous Marriage in Iran.

ERIC Educational Resources Information Center

Givens, Benjamin P.; Hirschman, Charles

1994-01-01

Used data on 4,667 women from the Iran Fertility Survey to examine trends and social correlates of consanguineous marriage. Found modest increase in proportion of marriages between cousins in Iran from 1940s to 1970s. Results suggest that modernization may be eroding social bases on consanguinity, whereas increased availability of cousins may lead…

Consanguinity Among Parents of Iranian Deaf Children

PubMed Central

Ajallouyan, Mohammad; Radfar, Shokofeh; Nouhi, Sima; Tavallaie, Seid Abbas; Amirsalari, Susan; Yousefi, Jaleh; Hasanali Fard, Mahdieh

2016-01-01

Background It seems that there is a relationship between consanguinity and profound hearing loss but there is little data about the association of consanguinity and hearing loss in Iran. Objectives The aim of this study is to demonstrate the causes of profound bilateral sensorineural hearing loss among Iranian samples who are candidates for cochlear implantation. Methods This study was retrospective, analytical, and designed to collect information about profound hearing impaired cases referred to the Baqiyatallah Cochlear implantation center using enumeration. A total of 310 children with profound hearing impairments participated in this study. They were aged from 6 months to 4 years old. The study was done between January 2007 and April 2009. Chi-square tests were used to show whether there was any statistical difference between the incidence of marital consanguinity of their parents and the normal population. Results Sixty-five percent of those 310 children had parents who had married with their relatives. Of the 203 (65%) parents that had consanguineous marriages, 132 were first cousins, which includes the children of two brothers (37 [11.8%] patrilateral parallel cousins), the children of two sisters (38 [12.2%] multi-lateral parallel cousins), or the children of a brother and a sister (57 [18.3%] cross cousins). Fifty-four (17.4%) of the parents were second cousins and 17 (5.2%) were beyond second cousins. Also, hearing loss etiology was obvious in 237 (76.3%) of the patients with profound hearing loss but was unknown in 73 (23.7%). Hereditary was identified as the most common cause in 33% of the cases. Conclusions Our data demonstrated a 65% occurrence of consanguineous marriage among the parents of deaf children, which is statistically different from the percentage of consanguineous marriage among Iranian population (38%). This indicates an obvious relationship between severe hearing loss and consanguineous marriage. PMID:28191326

Consanguinity Among Parents of Iranian Deaf Children.

PubMed

Ajallouyan, Mohammad; Radfar, Shokofeh; Nouhi, Sima; Tavallaie, Seid Abbas; Amirsalari, Susan; Yousefi, Jaleh; Hasanali Fard, Mahdieh

2016-11-01

It seems that there is a relationship between consanguinity and profound hearing loss but there is little data about the association of consanguinity and hearing loss in Iran. The aim of this study is to demonstrate the causes of profound bilateral sensorineural hearing loss among Iranian samples who are candidates for cochlear implantation. This study was retrospective, analytical, and designed to collect information about profound hearing impaired cases referred to the Baqiyatallah Cochlear implantation center using enumeration. A total of 310 children with profound hearing impairments participated in this study. They were aged from 6 months to 4 years old. The study was done between January 2007 and April 2009. Chi-square tests were used to show whether there was any statistical difference between the incidence of marital consanguinity of their parents and the normal population. Sixty-five percent of those 310 children had parents who had married with their relatives. Of the 203 (65%) parents that had consanguineous marriages, 132 were first cousins, which includes the children of two brothers (37 [11.8%] patrilateral parallel cousins), the children of two sisters (38 [12.2%] multi-lateral parallel cousins), or the children of a brother and a sister (57 [18.3%] cross cousins). Fifty-four (17.4%) of the parents were second cousins and 17 (5.2%) were beyond second cousins. Also, hearing loss etiology was obvious in 237 (76.3%) of the patients with profound hearing loss but was unknown in 73 (23.7%). Hereditary was identified as the most common cause in 33% of the cases. Our data demonstrated a 65% occurrence of consanguineous marriage among the parents of deaf children, which is statistically different from the percentage of consanguineous marriage among Iranian population (38%). This indicates an obvious relationship between severe hearing loss and consanguineous marriage.

Consanguineous marriages in the genetic counseling centers of Isfahan and the ethical issues of clinical consultations

PubMed Central

Nouri, Narges; Nouri, Nayereh; Tirgar, Samane; Soleimani, Elham; Yazdani, Vida; Zahedi, Farzaneh; Larijani, Bagher

2017-01-01

Consanguineous marriage, which is common in many regions in the world, has absorbed much attention as a causative factor in raising the incidence of genetic diseases. The adverse effects may be attributed to the expression of the genes received from common ancestors and mortality and morbidity of the offspring. Iran has a high rate of consanguineous marriages. In recent years genetic counseling has come to be considered in health care services. This cross-sectional study was conducted in order to determine the prevalence and types of consanguineous marriages in the genetic clinics in Isfahan. We aimed to define the different types of marriages, specific categories of genetic disorders associated with consanguineous marriages, and mode of inheritance in the family tree. We also narratively reviewed the ethical aspects of the issue. The data were collected using a simple questionnaire. A total number of 1535 couples from urban and rural areas formed the study population. The marriages were classified according to the degree of the relationship between couples, including: double cousin, first cousin, first cousin once removed, second cousin and beyond second cousin. The SPSS software version 16 was used for data analysis. Data obtained through genetic counseling offered during a 5-year period revealed that 74.3% had consanguineous relationships, 62.3% were first cousins, 1% were double cousins and 7.8% were second cousins. In addition, 76% of the couples had at least one genetic disease in their family tree. Related ethical issues were also considered in this study, including autonomy and informed decision making, benefit and harm assessment, confidentiality, ethics in research, justice in access to counseling services, financial problems ethics, and the intellectual property of scientific success. PMID:29416832

The practice of consanguineous marriage in Oman: prevalence, trends and determinants.

PubMed

Islam, M Mazharul

2012-09-01

The practice of consanguineous marriage has been the culturally preferred form of marriage in most Arab and the Middle Eastern countries, including Oman, but due to a paucity of population-based data in the past there is a dearth of information about its form and dynamics in Oman. Recent national-level surveys allow this gap to be filled. This paper examines the prevalence, trends and determinants of consanguineous marriages in Oman using data from the 2000 Oman National Health Survey. The results indicate a very high prevalence of consanguineous marriage in Oman, as more than half (52%) of marriages are consanguineous. First cousin unions are the most common type of consanguineous unions, constituting 39% of all marriages and 75% of all consanguineous marriages. The study observed various patterns of consanguinity, some of them common with other Arab nations, and some unique in nature. Women's age at marriage, employment, place of childhood residence and geographical region appear to be significant determinants of consanguineous marriages. Consanguineous marriage shows a strong association with marital stability, early age at marriage and early-age childbearing. There has been no appreciable change in the prevalence of consanguineous unions in Oman over the last four decades despite massive socioeconomic development and modernization. However, recent marriage cohorts show slight declining trends. The results suggest that consanguinity is likely to remain stable in the future or decline at a slow rate. Specific health education and genetic counselling should be followed in line with WHO recommendations to minimize the negative health consequences of consanguinity for child health.

Consanguinity and pregnancy outcomes in a multi-ethnic, metropolitan European population.

PubMed

Becker, Rolf; Keller, Thomas; Wegner, Rolf-Dieter; Neitzel, Heidemarie; Stumm, Markus; Knoll, Ute; Stärk, Markus; Fangerau, Heiner; Bittles, Alan

2015-01-01

The aim of the present study was to assess the risk of major anomalies in the offspring of consanguineous couples, including data on the prenatal situation. Over 20 years (1993-2012), 35,391 fetuses were examined by prenatal sonography. In 675 cases (1.9%), parents were consanguineous, with 307 couples (45.5%) related as first cousins, 368 couples (54.5%) beyond first cousins. Detailed information was retrieved on 31,710 (89.6%) fetuses, (consanguineous 568: 1.8%). Overall prevalence of major anomalies among fetuses with non-consanguineous parents was 2.9% (consanguineous, 10.9%; first cousins, 12.4%; beyond first cousins, 6.5%). Adjusting the overall numbers for cases having been referred because of a previous index case, the prevalences were 2.8% (non-consanguineous) and 6.1% (consanguineous) (first cousin, 8.5%; beyond first cousin, 3.9%). Further adjustment for differential rates of trisomic pregnancies indicated 2.0%/5.9% congenital anomalies (non-consanguineous/consanguineous groups), that is, a consanguinity-associated excess of 3.9%, 6.1% in first cousin progeny and 1.9% beyond first cousin. The prevalence of major fetal anomalies associated with consanguinity is higher than in evaluations based only on postnatal life. It is important that this information is made available in genetic counselling programmes, especially in multi-ethnic and multi-religious communities, to enable couples to make informed decisions. © 2014 John Wiley & Sons, Ltd.

Consanguinity and its socio-biological parameters in Rahim Yar Khan District, Southern Punjab, Pakistan.

PubMed

Riaz, Hafiza Fizzah; Mannan, Shaheen; Malik, Sajid

2016-05-20

Rahim Yar Khan (RYK) District is a multi-ethnic assemblage of both ancient and migrated communities in Southern Punjab, Pakistan. There is a paucity of knowledge on the bio-demographic structure of this endogamous population. We have carried out a cross-sectional epidemiological study in RYK District and recruited 2174 random Muslim married females. Detailed account of marital union types, level of consanguinity, and subject's fertility, was taken. The analyses of these data revealed that consanguineous unions (CU) were 58.46 %, rendering an inbreeding coefficient (IC-F) = 0.0355. The CU were observed to be significantly higher in subjects originating from rural areas, speaking Saraiki language, illiterate or having a religious/Madarsa education only, and belonging to nuclear family type. The rate of consanguinity was also higher in subjects whose husbands were engaged in unskilled manual or skilled manual jobs, and had consanguinity in the parental generation. Multivariate logistic regression analyses revealed that variables like Saraiki language, illiteracy, reciprocal marriages, and parental consanguinity, were the significant predictors of CU in the subject. Among the first cousin unions (which constituted 52 % of all marriages), parallel-cousin and patrilineal unions were in the majority (54 and 57 %, respectively), and father's brother's daughter type had the highest representation (31 %). The analyses further demonstrated that fertility and mean live-births were significantly higher in women who had CU compared to the non-consanguineous (NCU) group (p < 0.006); and significantly higher number of sons per women were born to the mothers who had CU compared with the NCU sample (p = 0.0002). However, there were no differences in the CU and NCU samples with respect to pre- or post-natal mortalities and child morbidities. The scientific findings in RYK District are distinct from the observations in other Pakistani populations and clue to a unique nature

Consanguineous marriage and reproduction in Beirut, Lebanon.

PubMed

Khlat, M

1988-08-01

Effects of consanguineous marriages on couples' fertility and on offspring mortality were investigated in Beirut through a population-based health survey of 2,752 households. A multistage random sampling procedure was used, and information was obtained from all ever-married women in the household about their reproductive performance and genealogical relationship with spouse; demographic and socioeconomic information was also recorded. Twenty-five percent of all marriages were between relatives, and the spouses were first cousins in approximately 57% of all consanguineous marriages. Total pregnancies, live births, and living children were significantly higher among consanguineous couples than among nonconsanguineous ones, as was the proportion dead among children ever born. However, no difference remained in either fertility or mortality, when allowance was made for socioeconomic status, religious affiliation, and marriage duration. The issue of confounding is discussed, and the lack of significant pattern in the final analysis is interpreted as resulting from a long-term practice of consanguineous marriages.

The ideology of small family.

PubMed

Lakshminarayana, H D

1991-01-01

Data are obtained and analyzed from 4232 rural families of handloom weavers in Karnataka state, India. 60.20% families are small families with 6 or fewer family members, of whom 25% have 3 members. 96.78% of small families have only one occupation. 30.50% of large families and 12.42% of medium sized families have more than one occupation. About 74% of families have income under the poverty line (under Rs 3500/year). 83% of small families are under the poverty line. The dependency ratio of small families is 1:2. 33% of all dependents are found among small families which are below the poverty line. 82% of dependents in small families are in small families under the poverty line. Almost 50% of dependents belong to small families. Small families are found to have slightly lower levels of education, although average level of education is very similar regardless of family size. The findings are used as evidence that small families do not necessarily augment the economy and that economic, educational, and cultural thresholds may be necessary before small family size affects economic development and improves the general well-being of family members. The social system that the small family is operating in is considered an important factor affecting the quality of life of the family.

Consanguinity, prematurity, birth weight and pregnancy loss: a prospective cohort study at four primary health center areas of Karnataka, India.

PubMed

Bellad, M B; Goudar, S S; Edlavitch, S A; Mahantshetti, N S; Naik, V; Hemingway-Foday, J J; Gupta, M; Nalina, H R; Derman, R; Moss, N; Kodkany, B S

2012-06-01

To determine whether consanguinity adversely influences pregnancy outcome in South India, where consanguinity is a common means of family property retention. Data were collected from a prospective cohort of 647 consenting women, consecutively registered for antenatal care between 14 and 18 weeks gestation, in Belgaum district, Karnataka in 2005. Three-generation pedigree charts were drawn for consanguineous participants. χ (2)-Test and Student's t-test were used to assess categorical and continuous data, respectively, using SPSS version 14. Multivariate logistic regression adjusted for confounding variables. Overall, 24.1% of 601 women with singleton births and outcome data were consanguineous. Demographic characteristics between study groups were similar. Non-consanguineous couples had fewer stillbirths (2.6 vs 6.9% P=0.017; adjusted P=0.050), miscarriages (1.8 vs 4.1%, P=0.097; adjusted P=0.052) and lower incidence of birth weight <2500 g (21.8 vs 29.5%, P=0.071, adjusted P=0.044). Gestation <37 weeks was 6.2% in both the groups. Adjusted for consanguinity and other potential confounders, age <20 years was protective of stillbirth (P=0.01), pregnancy loss (P=0.023) and preterm birth (P=0.013), whereas smoking (P=0.015) and poverty (P=0.003) were associated with higher rates of low birth weight. Consanguinity significantly increases pregnancy loss and birth weight <2500 g.

Effect of Consanguinity on Low Birth Weight: A Meta-Analysis.

PubMed

Poorolajal, Jalal; Ameri, Pegah; Soltanian, Alireza; Bahrami, Masoud

2017-03-01

Consanguinity (when couples share at least one common ancestor) is a public health issue with a variety of distributions and incidence rates worldwide. Several epidemiological studies have explored the association between consanguinity and low birth weight (LBW). However, the results are inconsistent. This meta-analysis aimed to explore the overall association between consanguineous marriage and LBW. We searched PubMed, Web of Science, Scopus, ScienceDirect, and reference lists of articles up to May 2015. We included cohort, case-control, and cross-sectional studies addressing the association between consanguinity and LBW. We assessed heterogeneity using Q-test and I2 statistic. We explored publication bias using the Egger's and Begg's tests and the funnel plot. We meta-analyzed the data and reported the overall odds ratio (OR) and mean difference with 95% confidence intervals (CI) using the random-effects model. We included 24 out of 3941 retrieved studies, with 44,131 participants. We indicated that LBW was associated significantly with first-cousin marriages (OR = 1.36; 95% CI: 1.03, 1.69) and non-significantly with second-cousin marriages (OR = 1.20; 95% CI: 0.49, 1.91). Furthermore, first-cousin marriages can reduce the birth weight of siblings of consanguineous couples 144 g more compared to non-consanguineous marriages. This meta-analysis measured the association between consanguinity and LBW. Based on the current evidence, consanguineous marriage can increase the risk for LBW. However, further evidence based on large cohort studies conducted in different settings is required to make a robust conclusion regarding the effect of consanguinity on LBW.

Prevalence of consanguineous marriages and associated factors among Israeli Bedouins.

PubMed

Na'amnih, Wasef; Romano-Zelekha, Orly; Kabaha, Ahmed; Rubin, Liza Pollack; Bilenko, Natalya; Jaber, Lutfi; Honovich, Mira; Shohat, Tamy

2014-10-01

The Bedouin population in Israel is a semi-nomadic traditional patriarchal society. Consanguineous marriages are very common, contributing to high rates of congenital malformations and genetic diseases, resulting in high infant mortality. Data on consanguineous marriages among Bedouins in Israel are limited. This study examined the current prevalence of consanguineous marriages and their determinants among Israeli Bedouins. One thousand two hundred ninety Bedouin women who delivered in the maternity wards of the only hospital serving the Bedouin population were interviewed between November 2009 and January 2010. The prevalence of consanguineous marriages was 44.8 %. The most common type of spousal relationship was first cousins (65.7 % of all consanguineous marriages). The mean inbreeding coefficient was 0.0238. Factors significantly associated with consanguinity were less years of schooling (OR 0.94, 95 % CI (0.88-0.99), p = 0.02) and younger age at marriage of the wife (OR 0.90, 95 % CI (0.80-0.96), p = 0.0002). In conclusion, the rate of consanguineous marriages among Bedouins is very high, making this population at risk for congenital malformations and genetic diseases. Efforts should be directed at better education and provision of premarital and prenatal counseling on the health consequences of consanguineous marriages and the possibilities to lower those risks.

The Implications of Parental Consanguinity on the Care of Neonates.

PubMed

Ng, Diana

2016-08-01

Approximately 6% of births worldwide, 7.9 million children, are born with a serious genetic congenital abnormality each year. A factor thought to increase the prevalence of birth defects is parental consanguinity, which is a social custom practiced in at least 20% of the world's population. The purpose of this article is to explore the relationship between consanguinity and congenital defects. This article also aims to enhance neonatal healthcare practitioners' comprehension of its implications for practice and research. A review of literature was compiled from a search of the online databases Cumulative Index of Nursing and Allied Health (CINAHL), PubMed, EBSCO MegaFILE, and Google Scholar. Literature pertinent to this topic primarily consists of research studies that examine the inbreeding depression phenomenon through comparison of the prevalence of birth defects among the offspring of consanguineous and nonconsanguineous couples. Current studies indicate that the progeny of consanguineous couples are at an increased risk of congenital defects compared with those of nonconsanguineous couples. Consanguinity is one risk factor among many that can lead to a major birth defect. Relationships between consanguineous populations and neonatal healthcare practitioners such as registered nurses, advanced practice nurses, and physicians could significantly alter neonatal health outcomes. Specific recommendations such as genetic counseling and therapeutic communication are discussed. Further studies need to investigate the connection between consanguinity and birth defects while controlling for nongenetic variables. Moreover, a focus on consanguineous communities in the United States would prove beneficial.

Socioeconomic, demographic, and geographic variables affecting the diverse degrees of consanguineous marriages in Spain.

PubMed

Fuster, V; Colantonio, S E

2004-02-01

In a population the inbreeding coefficient alpha is determined by the relative incidence of the various degrees of consanguineous marriages--uncle-niece or aunt-nephew (C12), first cousin (C22), first cousin once removed (C23), second cousin (C33)--which may be related to temporal, geographic, demographic, and economic factors. Using published information from Spain corresponding to urban and rural areas, in this article we seek to establish how each specific relationship behaves with respect to geographic, demographic, and socioeconomic factors, to determine differential urban-rural patterns, and to study whether the diverse types of consanguineous matings relate homogeneously to these factors. For this purpose we performed multiple regressions in which the dependent variables were the different degrees of consanguinity previously selected and the independent variables were geographic, demographic, and economic factors. Our results indicate that the various types of consanguineous marriages in Spain are more conditioned by geographic, demographic, and economic variables than by the inbreeding level alpha (the coefficient of determination was between 0.22 and 0.72; the maximum for alpha was 0.35). A regional pattern exists in Spain and corresponds to close and to remote kinship, which may be mainly related to economic and family factors. Close relationships appear to be more associated with economic variables, whereas second-cousin marriages correspond largely to rural areas of the Spanish Central Plateau.

A novel mutation in PGAP2 gene causes developmental delay, intellectual disability, epilepsy and microcephaly in consanguineous Saudi family.

PubMed

Naseer, Muhammad Imran; Rasool, Mahmood; Jan, Mohammed M; Chaudhary, Adeel G; Pushparaj, Peter Natesan; Abuzenadah, Adel M; Al-Qahtani, Mohammad H

2016-12-15

PGAP2 (Post-GPI Attachment to Proteins 2) gene is involved in lipid remodeling steps of Glycosylphosphatidylinositol (GPI)-anchor maturation. At the surface of the cell this gene is required for proper expression of GPI-anchored proteins. Hyperphosphatasia with mental retardation syndrome-3 is an autosomal recessive disorder usually characterized by severe mental retardation. Mutations in the PGAP2 gene cause hyperphosphatasia mental retardation syndrome-3. We have identified a large consanguineous family from Saudi origin segregating developmental delay, intellectual disability, epilepsy and microcephaly. Whole exome sequencing with 100× coverage was performed on two affected siblings of the family. Data analysis in the patient revealed a novel missense mutation c.191C>T in PGAP2 gene resulting in Alanine to Valine substitution (Ala64Val). The mutation was reconfirmed and validated by subsequent Sanger sequencing method. The mutation was ruled out in 100 unrelated healthy controls. We suggest that this pathogenic mutation disrupts the proper function of the gene proteins resulting in the disease state. Copyright © 2016 Elsevier B.V. All rights reserved.

Organ donation consanguinity or universality.

PubMed

Kishore, R R

1996-01-01

1. Neither the "Diseased Persons" nor the "Genetic Relations" provide an answer to "trading" in human body parts. 2. Live human body constitutes a vital source of supply of organs and tissues and the possibilities of optimum utilisation should be explored. 3. There is no scope for dogmatic postures and open-mindedness should be the approach while dealing with the issue of Organ Transplantation. 4. Society owes a duty to save the file of a dying man and in the event of failure to do so, it is absolutely immoral to interfere with his own arrangements by making unrealistic laws. No immorality is involved if an individual disposes of his spare body parts for a valid consideration to a needy person. 5. The scarcity needs to be urgently overcome otherwise unwarranted trade and crime are liable to thrive. 6. Families are not unconnected or antagonistic fragments of humanity. After thousands of years of continuous efforts the individuals on this earth have attained the stage of organic and functional integration. Atomisation of society on the basis of consanguineous proximities amounts to reversing this holistic trend. Organ transplantation is a functional expression of a highly evolved pursuit with inherent and intimate interaction in the form of organic exchange at the individual level, independent of consanguineous inducements or motivations. As such there is absolutely no scope for restricting organ donations by strangers. 7. Commercialisation should be curbed by making the enforcement agencies more efficient and not by depriving a needy person of his genuine requirements. Legislative craftsmanship lies in providing an answer without curtailing the freedom of the people.

Homozygosity mapping in 64 Syrian consanguineous families with non-specific intellectual disability reveals 11 novel loci and high heterogeneity

PubMed Central

Abou Jamra, R; Wohlfart, Sigrun; Zweier, Markus; Uebe, Steffen; Priebe, Lutz; Ekici, Arif; Giesebrecht, Susanne; Abboud, Ahmad; Al Khateeb, Mohammed Ayman; Fakher, Mahmoud; Hamdan, Saber; Ismael, Amina; Muhammad, Safia; Nöthen, Markus M; Schumacher, Johannes; Reis, André

2011-01-01

Non-specific intellectual disability of autosomal recessive inheritance (NS-ARID) represents an important fraction of severe cognitive dysfunction disorders. To date, only 10 genes have been identified, and further 24 linked-ARID loci have been reported, as well as others with suggestive linkage. To discover novel genes causing NS-ARID, we undertook genome-wide homozygosity mapping in 64 consanguineous multiplex families of Syrian descent. A total of 11 families revealed unique, significantly linked loci at 4q26-4q28 (MRT17), 6q12-q15 (MRT18), 18p11 (MRT19), 16p12-q12 (MRT20), 11p15 (MRT21), 11p13-q14 (MRT23), 6p12 (MRT24), 12q13-q15 (MRT25), 14q11-q12 (MRT26), 15q23-q26 (MRT27), and 6q26-q27 (MRT28), respectively. Loci ranged between 1.2 and 45.6 Mb in length. One family showed linkage to chromosome 8q24.3, and we identified a mutation in TRAPPC9. Our study further highlights the extreme heterogeneity of NS-ARID, and suggests that no major disease gene is to be expected, at least in this study group. Systematic analysis of large numbers of affected families, as presented here, will help discovering the genetic causes of ID. PMID:21629298

WDR73 missense mutation causes infantile onset intellectual disability and cerebellar hypoplasia in a consanguineous family.

PubMed

Jiang, Chen; Gai, Nan; Zou, Yongyi; Zheng, Yu; Ma, Ruiyu; Wei, Xianda; Liang, Desheng; Wu, Lingqian

2017-01-01

Galloway-Mowat syndrome (GMS) is a very rare autosomal-recessive disorder characterized by nephrotic syndrome associated with microcephaly, and various central nervous system abnormalities, mostly cerebral hypoplasia or cerebellar atrophy, intellectual disability and neural-migration defects. WDR73 is the only gene known to cause GMS, and has never been implicated in other disease. Here we present a Chinese consanguineous family with infantile onset intellectual disability and cerebellar hypoplasia but no microcephaly. Whole exome sequencing identified a WDR73 p.W371G missense mutation. The mutation is confirmed to be segregated in this family by Sanger sequencing according to a recessive inheritance pattern. It is predicted to be deleterious by multiple algorithms and affect highly conserved site. Structural modeling revealed conformational differences between the wild type protein and the p.W371G protein. Real-time PCR and Western blotting revealed altered mRNA and protein levels in mutated samples. Our study indicates the novel WDR73 p.W371G missense mutation causes infantile onset intellectual disability and cerebellar hypoplasia in recessive mode of inheritance. Our findings imply that microcephaly is a variable phenotype in WDR73-related disease, suggest WDR73 to be a candidate gene of severe intellectual disability and cerebellar hypoplasia, and expand the molecular spectrum of WDR73-related disease. Copyright © 2016 Elsevier B.V. All rights reserved.

Parental consanguinity and associated factors in congenital talipes equinovarus.

PubMed

Sreenivas, T; Nataraj, A R

2012-03-01

The cause of congenital talipes equinovarus (CTEV) is multifactorial and, consanguinity could be one of the causative factors in its development. The purpose of this study was, to determine the prevalence of parental consanguinity in CTEV and other factors like associated, congenital anomalies, maternal and fetal factors and also the severity of CTEV in these patients. The above factors were studied in 54 patients of less than 1 month of age with parental, consanguinity and 91 feet were evaluated for its severity using Dimeglio classification at the time of presentation. Out of 174 children presented to our department with CTEV, 54 (31%) children were born out, of consanguineous marriage. Thirty seven (68.5%) patients had bilateral CTEV. Twenty five (46.3%), patients had associated congenital anomalies and myelomeningocele being the commonest anomaly, associated. Out of 91 feet 61 (67%) were of grade 4 severity. High grade of severity observed in both idiopathic and non idiopathic CTEV suggests the, probable role of consanguinity as an etiological factor in the development of CTEV especially in our, part of the world. Copyright © 2011 Elsevier Ltd. All rights reserved.

The relationship between consanguineous marriage and death in fetus and infants.

PubMed

Mohammadi, Majid Mehr; Hooman, Heidar Ali; Afrooz, Gholam Ali; Daramadi, Parviz Sharifi

2012-05-01

Given the high prevalence of consanguineous marriages in rural and urban areas of Iran, the aim of this study was to identify its role in increasing fetal and infant deaths. This was a cross-sectional study in which 494 mothers with more than one exceptional child (mentally retarded and physically-dynamically disabled) or with normal children were selected based on multi-stage random sampling method. Data was gathered using the features of parents with more than one exceptional child questionnaire. The validity and reliability of this questionnaire was acceptable. Hierarchical log-linear method was used for statistical analysis. Consanguineous marriage significantly increased the number of births of exceptional children. Moreover, there was a significant relation between the history of fetal/infant death and belonging to the group. There was a significant relation between consanguineous marriage and the history of fetal/infant death which means consanguineous marriage increased the prevalence of fetal/infant death in parents with exceptional children rather than in parents with normal children. The rate of fetal/infant death in exceptional births of consanguineous marriages was higher than that of non-consanguineous marriages.

The relationship between consanguineous marriage and death in fetus and infants

PubMed Central

Mohammadi, Majid Mehr; Hooman, Heidar Ali; Afrooz, Gholam Ali; Daramadi, Parviz Sharifi

2012-01-01

Background: Given the high prevalence of consanguineous marriages in rural and urban areas of Iran, the aim of this study was to identify its role in increasing fetal and infant deaths. Materials ans Methods: This was a cross-sectional study in which 494 mothers with more than one exceptional child (mentally retarded and physically-dynamically disabled) or with normal children were selected based on multi-stage random sampling method. Data was gathered using the features of parents with more than one exceptional child questionnaire. The validity and reliability of this questionnaire was acceptable. Hierarchical log-linear method was used for statistical analysis. Results: Consanguineous marriage significantly increased the number of births of exceptional children. Moreover, there was a significant relation between the history of fetal/infant death and belonging to the group. There was a significant relation between consanguineous marriage and the history of fetal/infant death which means consanguineous marriage increased the prevalence of fetal/infant death in parents with exceptional children rather than in parents with normal children. Conclusions: The rate of fetal/infant death in exceptional births of consanguineous marriages was higher than that of non-consanguineous marriages. PMID:23626609

Exome Sequencing Discerns Syndromes in Patients from Consanguineous Families with Congenital Anomalies of the Kidneys and Urinary Tract

PubMed Central

Vivante, Asaf; Hwang, Daw-Yang; Kohl, Stefan; Chen, Jing; Shril, Shirlee; Schulz, Julian; van der Ven, Amelie; Daouk, Ghaleb; Soliman, Neveen A.; Kumar, Aravind Selvin; Senguttuvan, Prabha; Kehinde, Elijah O.; Tasic, Velibor

2017-01-01

Congenital anomalies of the kidneys and urinary tract (CAKUT) are the leading cause of CKD in children, featuring a broad variety of malformations. A monogenic cause can be detected in around 12% of patients. However, the morphologic clinical phenotype of CAKUT frequently does not indicate specific genes to be examined. To determine the likelihood of detecting causative recessive mutations by whole-exome sequencing (WES), we analyzed individuals with CAKUT from 33 different consanguineous families. Using homozygosity mapping and WES, we identified the causative mutations in nine of the 33 families studied (27%). We detected recessive mutations in nine known disease–causing genes: ZBTB24, WFS1, HPSE2, ATRX, ASPH, AGXT, AQP2, CTNS, and PKHD1. Notably, when mutated, these genes cause multiorgan syndromes that may include CAKUT as a feature (syndromic CAKUT) or cause renal diseases that may manifest as phenocopies of CAKUT. None of the above monogenic disease–causing genes were suspected on clinical grounds before this study. Follow-up clinical characterization of those patients allowed us to revise and detect relevant new clinical features in a more appropriate pathogenetic context. Thus, applying WES to the diagnostic approach in CAKUT provides opportunities for an accurate and early etiology–based diagnosis and improved clinical management. PMID:27151922

Prevalence of consanguineous marriages in west and south of Afghanistan.

PubMed

Saadat, Mostafa; Tajbakhsh, Khadijeh

2013-11-01

The prevalence of consanguinity in eight provinces of Afghanistan has recently been reported by Saify & Saadat (2012). The present cross-sectional study was done in order to illustrate the prevalence and types of consanguineous marriages among other populations of Afghanistan. Data on types of marriages were collected using a simple questionnaire. The total number of couples in this study was 5200 from the following provinces: Farah, Ghazni, Herat, Hilmand, Kabul, Kandahar, Logar, Parwan and Wardak. Consanguineous marriages were classified by the degree of relationship between couples: double first cousins, first cousins, first cousins once removed, second cousins and beyond second cousins. The coefficient of inbreeding (F) was calculated for each couple and the mean coefficient of inbreeding (α) estimated for each population. The α in the country was 0.0226, ranging from 0.0203 in Farah province to 0.0246 in Herat province. There were significant differences between provinces for frequencies of different types of marriages (p<0.001). First cousin marriages (21.7%) were the most common type of consanguineous marriages, followed by second cousins (16.0%), first cousins once removed (14.0%), beyond second cousins (6.9%) and double first cousins (1.6%). There was significant difference between ethnic groups for the types of marriages (p<0.001). Tajiks (Soni) and Sadats showed the lowest (α=0.0215) and highest (α=0.0242) levels of consanguinity among ethnic groups in Afghanistan, respectively. The present study shows that the Afghani populations, the same as other Islamic populations, have high levels of consanguinity.

CONSANGUINITY AND INBREEDING COEFFICIENT IN TRIBAL PASHTUNS INHABITING THE TURBULENT AND WAR-AFFECTED TERRITORY OF BAJAUR AGENCY, NORTH-WEST PAKISTAN.

PubMed

Ahmad, Bashir; Rehman, Atta Ur; Malik, Sajid

2016-01-01

The north-western populations of Pakistan in the Federally Administered Tribal Areas (FATA) adjoining the Pakistan-Afghanistan border are an amalgamation of native and migrated Pashtun tribes. These tribal populations are in transition due to war conditions and geo-political turmoil on both sides of the border since the Soviet invasion in 1979. Bio-demographic and epidemiological data for these tribes are scarce. A prospective cross-sectional sample of 967 males was selected from a representative Pashtun population of Bajaur Agency, and information obtained on bio-demographic variables and marital union types. Analysis of these data revealed that consanguinity was 22.34% and the inbreeding coefficient F was calculated to be 0.0134. The inbreeding coefficient was observed to be higher in subjects who were illiterate, had unskilled jobs and who belonged to younger age categories, extended families and the Tarkalani tribe. Further analyses with respect to temporal variables like subject's age, year of marriage and age at marriage revealed that after a transition in marital union types in the early 80s, there has been a declining trend in the rate of consanguineous unions. Further, consanguineous unions in the parental generation were only 5%, but parental marriage types were predictors of subjects' marital union types. The data further establish that, contrary to a general notion about a high consanguinity rate in Pakistan, consanguineous unions are not common in Bajaur Agency and first cousin marriage is not the preferred type. Furthermore, this research shows that there is a great regional variation in the pattern of consanguinity in Pakistan that needs to be documented in order to draw a more comprehensive picture of the inbreeding coefficient in the country.

Exome Sequencing Discerns Syndromes in Patients from Consanguineous Families with Congenital Anomalies of the Kidneys and Urinary Tract.

PubMed

Vivante, Asaf; Hwang, Daw-Yang; Kohl, Stefan; Chen, Jing; Shril, Shirlee; Schulz, Julian; van der Ven, Amelie; Daouk, Ghaleb; Soliman, Neveen A; Kumar, Aravind Selvin; Senguttuvan, Prabha; Kehinde, Elijah O; Tasic, Velibor; Hildebrandt, Friedhelm

2017-01-01

Congenital anomalies of the kidneys and urinary tract (CAKUT) are the leading cause of CKD in children, featuring a broad variety of malformations. A monogenic cause can be detected in around 12% of patients. However, the morphologic clinical phenotype of CAKUT frequently does not indicate specific genes to be examined. To determine the likelihood of detecting causative recessive mutations by whole-exome sequencing (WES), we analyzed individuals with CAKUT from 33 different consanguineous families. Using homozygosity mapping and WES, we identified the causative mutations in nine of the 33 families studied (27%). We detected recessive mutations in nine known disease-causing genes: ZBTB24, WFS1, HPSE2, ATRX, ASPH, AGXT, AQP2, CTNS, and PKHD1 Notably, when mutated, these genes cause multiorgan syndromes that may include CAKUT as a feature (syndromic CAKUT) or cause renal diseases that may manifest as phenocopies of CAKUT. None of the above monogenic disease-causing genes were suspected on clinical grounds before this study. Follow-up clinical characterization of those patients allowed us to revise and detect relevant new clinical features in a more appropriate pathogenetic context. Thus, applying WES to the diagnostic approach in CAKUT provides opportunities for an accurate and early etiology-based diagnosis and improved clinical management. Copyright © 2016 by the American Society of Nephrology.

Health problems, complex life, and consanguinity among ethnic minority Muslim women in Nepal.

PubMed

Bhatta, Dharma Nand; Haque, Anwarul

2015-01-01

Marriage between blood relatives is common among Muslim ethnic minority population in Nepal. Albeit, the adverse effects of such a consanguineous marriage on health are controversial. To determine the prevalence, characteristics and health outcomes related to consanguineous marriage. A cross-sectional survey was carried out using a cluster sampling technique to select the respondents. A total of 400 women aged 15-49 years were interviewed from September 2011 to February 2012. A structured questionnaire was administered through face-to-face meetings. Adjusted odds ratios (AOR) were estimated by a stepwise likelihood ratio method with binary logistic regression. The overall prevalence of consanguinity was 36.7%. The median age at marriage and age at first childbirth was 15 and 18 years, respectively. The association of being in a consanguineous marriage among women whose husband's education level were secondary or higher was 3.35 (95% CI 1.56, 7.12) times greater than among those whose husbands were unable to read and write. Woman who have consanguineous marriage were less likely to have (AOR 0.46, 95% CI 0.26, 0.82) used contraceptive than those who have non-consanguineous marriage. Women who have consanguineous marriage were more (AOR 1.80; 95% CI 0.90, 3.61) likely to have birth defect in their children than those who have non-consanguineous marriage. The association of having a history of death after live birth among women who experienced emotional violence was 2.60 (95% CI 1.36, 5.00) and physical violence 2.15 (95% CI 1.16, 3.93) times greater than among those who did not experience violence. Several factors like husband's education and dowry practices are associated with consanguineous marriage. Further, these factors including consanguineous marriage and marital violence are also accountable for negative health consequences. Thus, multicomponent interventions are needed in order to improve the health condition of Nepalese Muslim community in rural area.

CONSANGUINEOUS MARRIAGES AMONG IRANIAN MANDAEANS LIVING IN SOUTH-WEST IRAN.

PubMed

Saadat, Mostafa; Zarghami, Mahdis

2018-07-01

SummarySeveral studies have indicated that consanguineous marriages (unions between biologically related persons) are associated with increased risk of autosomal recessive diseases and several multifactorial traits. Mandaeans are a closed ethno-religious community living in areas of southern Iraq and Iran (Khuzestan Province). There are currently no data on the prevalence of consanguineous marriages among Mandaeans. The present study was carried out in 2016 to determine the prevalence of consanguinity among Iranian Mandaeans living in Khuzestan Province, south-west Iran. A total of 137 couples (urban areas: 79 couples; rural areas: 58 couples) were included in the study. Information on the consanguineous marriages of the subjects was collected through direct interviews. Marriages were classified by the degree of relationship between couples as double first cousins, first cousins, first cousin once removed, second cousins and unrelated marriages. The coefficient of inbreeding (F) was calculated for each couple and the mean coefficient of inbreeding (α) estimated for the population, stratified by rural and urban areas. The overall frequency of consanguinity was found to be 50.7% in urban and 86.2% in rural areas. There was a significant difference between rural and urban areas in types of marriages (χ 2=24.8, df=4, p<0.001) and first cousin marriages (51.8%) were the most common type. The overall α-value was estimated to be 0.0363 for the Iranian Mandaean population.

Homozygous missense mutation in the LMAN2L gene segregates with intellectual disability in a large consanguineous Pakistani family.

PubMed

Rafiullah, Rafiullah; Aslamkhan, Muhammad; Paramasivam, Nagarajan; Thiel, Christian; Mustafa, Ghulam; Wiemann, Stefan; Schlesner, Matthias; Wade, Rebecca C; Rappold, Gudrun A; Berkel, Simone

2016-02-01

Intellectual disability (ID) is a neurodevelopmental disorder affecting 1%-3% of the population worldwide. It is characterised by high phenotypic and genetic heterogeneity and in most cases the underlying cause of the disorder is unknown. In our study we investigated a large consanguineous family from Baluchistan, Pakistan, comprising seven affected individuals with a severe form of autosomal recessive ID (ARID) and epilepsy, to elucidate a putative genetic cause. Whole exome sequencing (WES) of a trio, including a child with ID and epilepsy and its healthy parents that were part of this large family, revealed a homozygous missense variant p.R53Q in the lectin mannose-binding 2-like (LMAN2L) gene. This homozygous variant was co-segregating in the family with the phenotype of severe ID and infantile epilepsy; unaffected family members were heterozygous variant carriers. The variant was predicted to be pathogenic by five different in silico programmes and further three-dimensional structure modelling of the protein suggests that variant p.R53Q may impair protein-protein interaction. LMAN2L (OMIM: 609552) encodes for the lectin, mannose-binding 2-like protein which is a cargo receptor in the endoplasmic reticulum important for glycoprotein transport. Genome-wide association studies have identified an association of LMAN2L to different neuropsychiatric disorders. This is the first report linking LMAN2L to a phenotype of severe ARID and seizures, indicating that the deleterious homozygous p.R53Q variant very likely causes the disorder. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Parental consanguinity and susceptibility to drug abuse among offspring, a case-control study.

PubMed

Saadat, Mostafa; Vakili-Ghartavol, Roghayyeh

2010-11-30

Consanguineous marriage is the union of individuals having at least one common ancestor. It is well established that consanguinity is a potential risk factor for many adverse health outcome of offspring. In the present case-control study we tested the hypothesis of an association between parental consanguinity marriages and risk of offspring substance abuse. The study was performed in Shiraz (Fars province, Iran). Here 156 male drug abusers (case group) and 264 randomly selected healthy blood donors, matched for age and gender as control group, were included in the study. The prevalence of parental consanguineous marriages in the studied sample was 39.1 and 28.0% among cases and controls, respectively. The difference was statistically significant. The substance abusers were more smokers and drinkers compared with the control group. There was significant negative linear trend between drug abuse and level of education. The participants stratified using drinking habits and then the analysis was carried out separately for drinker and non-drinker subjects. Among drinkers, neither before nor after adjusting for smoking status and educational level, parental consanguinity did not show association with risk of substance abuse. Among non-drinkers, after adjusting for smoking status and educational level, parental consanguineous marriage was significantly associated with increased risk of substance abuse. Our study supports a significant relationship between parental consanguinity and drug abuse among non-drinker subjects. Copyright © 2010 Elsevier Ltd. All rights reserved.

Modernization or cultural maintenance: the practice of consanguineous marriage in Iran.

PubMed

Jalal Abbasi-Shavazi, Mohammad; McDonald, Peter; Hosseini-Chavoshi, Meimanat

2008-11-01

Consanguineous marriage has been the culturally preferred form of marriage in Iran. This paper examines the extent to which education, urbanization and changes in modes of economic production have affected the incidence of consanguineous marriage and attitudes towards consanguineous marriages. The 2002 Iran Fertility Transition Survey conducted in the four provinces of Gilan, Sistan and Baluchistan, Yazd and West Azarbaijan provides information on the degree of relationship of marriage partners from around 6550 ever-married women aged 15-49. Attitudinal data were also obtained. Overall, the level of marriage to biological relatives ranged from 23% in Gilan to 78% in Sistan and Baluchistan. The paper finds that the practice of marriage to biological relatives has remained surprisingly resilient in the face of modernizing influences and that ethnicity, province and area of residence remain important determinants. On the other hand, attitudes have shifted towards marriage with a non-relative. Anthropological research would illuminate the processes of consanguineous marriage in Iran.

Prevalence of consanguineous marriages among shi'a populations of Lebanon.

PubMed

El-Kheshen, Ghadir; Saadat, Mostafa

2013-09-01

In genetics, a consanguineous marriage means union between couples who are related as second cousins or closer. The present cross-sectional study was carried out in order to illustrate the prevalence and types of consanguineous marriages in the Shi'a population living in widespread territories in Lebanon including the Bekaa Valley, the south of Lebanon and the southern suburb of Beirut. Data on types of marriages were collected using a simple questionnaire. The total number of couples in the study was 1203. Consanguineous marriage was classified by the degree of relationship between couples. The overall frequency of consanguinity was found to be 28.4%, with first cousin marriages (21.3%) being the most common type followed by first cousins once removed (5.5%), then double first cousins (0.8%). The frequencies of second cousin and beyond second cousin marriages were the same at 0.4% of all the marriages. The mean inbreeding coefficient (α) was estimated at about 0.0161 for the population. There were no significant differences between the three studied territories for frequencies of different types of marriages (p>0.1), nor were there significant differences between the rural and urban areas (p>0.1).

Consanguineous marriages and matrimonial distance: a study among three South Indian caste groups.

PubMed

Reddy, P G

1988-12-01

Reddy studies consanguineous marriages and matrimonial distance in 3 castes of Nellore district, Andhra Pradesh, South India. The castes include the well-to-do agricultural caste, the Desuri Kapu; the 2nd, artisan caste in the middle of the hierarchy, the Devanga; and the third caste at the bottom of the social ladder, the Mala. During field work conducted in 1978-1979, prominent elders of the villages were approached; information on the consanguinity of marriage and matrimonial distance was gathered through intensive interviews of both men and women from all the households of the 3 castes. Among the total of 979 marriages, 28.9% occurred within the village, the proportion of intra-village marriages being significantly higher in Nellore taluk than in Sullurpet. The 3 castes overall show little difference in the incidence of intra-village marriages, but there is some within caste regional variation in the incidence of intra-village marriages, the Devanga showing a significantly higher incidence in Nellore than in Sullurpet. Intra-village marriages are more common among consanguineous couples (41.5%) than among non-consanguineous (18.3%), a highly significant excess in each of the caste groups. In short, Reddy concludes that intra-village marriages are more common among consanguineous couples than non-consanguineous, and mean matrimonial distance is also lower.

A Mitochondrial DNA A8701G Mutation Associated with Maternally Inherited Hypertension and Dilated Cardiomyopathy in a Chinese Pedigree of a Consanguineous Marriage

PubMed Central

Zhu, Ye; Gu, Xiang; Xu, Chao

2016-01-01

Background: Cardiovascular diseases, including dilated cardiomyopathy (DCM) and hypertension, are the leading cause of death worldwide. The role of mitochondrial DNA (mtDNA) in the pathogenesis of these diseases has not been completely clarified. In this study, we evaluate whether A8701G mutation is associated with maternally inherited hypertension and DCM in a Chinese pedigree of a consanguineous marriage. Methods: Fourteen subjects in a three-generation Han Chinese family with hypertension and DCM, in which consanguineous marriage was present in the parental generation, were interviewed. We divided all the family members into case (7 maternal members) and control group (7 nonmaternal members) for comparison. Clinical evaluations and sequence analysis of mtDNA were obtained from all participants. Frequency differences between maternal and nonmaternal members were tested to locate the disease-associated mutations. Results: The majority of the family members presented with a maternal inheritance of hypertension and DCM. Sequence analysis of mtDNA in this pedigree identified eight mtDNA mutations. Among the mutations identified, there was only one significant mutation: A8701G (P = 0.005), which is a homoplasmic mitochondrial missense mutation in all the matrilineal relatives. There was no clear evidence for any synergistic effects between A8701G and other mutations. Conclusions: A8701G mutation may act as an inherited risk factor for the matrilineal transmission of hypertension and DCM in conjunction with genetic disorders caused by consanguineous marriage. PMID:26831225

Genetics of consanguineous marriage: Impact and importance of counseling.

PubMed

Akrami, Seyed Mohammad

2012-12-01

Consanguineous marriage, marriage between close biological kin, especially that between first cousins, is socially favored in some parts of North Africa, the Middle East and Asia. An increased rate of congenital anomalies and autosomal recessive disorders are significantly associated with such practice. In such communities, misunderstanding and external attempts to discourage such marriage without proper genetic counseling seem to be inappropriate and unsuccessful. Update in knowledge of clinicians especially pediatricians is the aim of this paper regarding importance and issues behind consanguineous marriage.

Novel homozygous missense mutation in GAN associated with Charcot-Marie-Tooth disease type 2 in a large consanguineous family from Israel.

PubMed

Aharoni, Sharon; Barwick, Katy E S; Straussberg, Rachel; Harlalka, Gaurav V; Nevo, Yoram; Chioza, Barry A; McEntagart, Meriel M; Mimouni-Bloch, Aviva; Weedon, Michael; Crosby, Andrew H

2016-11-16

CMT-2 is a clinically and genetically heterogeneous group of peripheral axonal neuropathies characterized by slowly progressive weakness and atrophy of distal limb muscles resulting from length-dependent motor and sensory neurodegeneration. Classical giant axonal neuropathy (GAN) is an autosomal recessively inherited progressive neurodegenerative disorder of the peripheral and central nervous systems, typically diagnosed in early childhood and resulting in death by the end of the third decade. Distinctive phenotypic features are the presence of "kinky" hair and long eyelashes. The genetic basis of the disease has been well established, with over 40 associated mutations identified in the gene GAN, encoding the BTB-KELCH protein gigaxonin, involved in intermediate filament regulation. An Illumina Human CytoSNP-12 array followed by whole exome sequence analysis was used to identify the disease associated gene mutation in a large consanguineous family diagnosed with Charcot-Marie-Tooth disease type 2 (CMT-2) from which all but one affected member had straight hair. Here we report the identification of a novel GAN missense mutation underlying the CMT-2 phenotype observed in this family. Although milder forms of GAN, with and without the presence of kinky hair have been reported previously, a phenotype distinct from that was investigated in this study. All family members lacked common features of GAN, including ataxia, nystagmus, intellectual disability, seizures, and central nervous system involvement. Our findings broaden the spectrum of phenotypes associated with GAN mutations and emphasize a need to proceed with caution when providing families with diagnostic or prognostic information based on either clinical or genetic findings alone.

Potential social, economic and general health benefits of consanguineous marriage: results from the Born in Bradford cohort study.

PubMed

Bhopal, Raj S; Petherick, Emily S; Wright, John; Small, Neil

2014-10-01

More than 1 billion people live in societies where consanguineous marriages are common. When children are born to consanguineous unions, there is an increased probability of the expression of single-gene disorders with a recessive mode of inheritance. There are presumptive social benefits of consanguineous marriages reported in the literature. The UK's Born in Bradford birth cohort study recruited 12 453 women at 26-28 weeks' gestation between 2007 and 2010. In all, 11 396 completed a questionnaire, including questions about their relationship to their baby's father. We compared Pakistani and Other ethnic groups in consanguineous relationships and Pakistani, Other and White British groups not in consanguineous relationships, calculating percentages and age-adjusted prevalence ratios (95% confidence intervals). In the Pakistani group, 59.3% of women (n = 3038) were blood relatives of their baby's father. Consanguinity was uncommon in the Other ethnic group (7.3%, n = 127) and rare (n = 5) in the White British group. Compared with non-consanguineous counterparts, mothers in consanguineous relationships were socially and economically disadvantaged (e.g. never employed, less likely to have higher education). The Pakistani consanguineous group's social, economic and health lifestyle circumstances were equivalent to, in some cases better than, women in non-consanguineous relationships (e.g. up-to-date in paying bills, or in disagreeing that they wished for more warmth in their marital relationship). The consanguineous relationship group had less separation/divorce. Rates of cigarette smoking during pregnancy were lower in mothers in consanguineous relationships. Debate about consanguinity should balance the potential protective effect of consanguineous relationships with established genetic risk of congenital anomaly in children. © The Author 2013. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

Clinical and molecular effect on offspring of a marriage of consanguineous spinocerebellar ataxia type 7 mutation carriers: a family case report

PubMed Central

Magaña, Jonathan J; Tapia-Guerrero, Yessica S; Velázquez-Pérez, Luis; Cruz-Mariño, Tania; Cerecedo-Zapata, Cesar M; Gómez, Rocío; Murillo-Melo, Nadia M; González-Piña, Rigoberto; Hernández-Hernández, Oscar; Cisneros, Bulmaro

2014-01-01

Spinocerebellar ataxia type 7 (SCA7) is a genetic disorder characterized by degeneration of the cerebellum, brainstem, and retina that is caused by abnormal expansion of a CAG repeat located in the ATXN7 gene encoding sequence on chromosome 3p21.1. Although SCA7 is an uncommon autosomal dominant ataxia, we previously found increased prevalence of the disease in a Southeastern Mexican population. In this study, we described to our knowledge for the first time a marriage of consanguineous SCA7 mutation carriers and their offspring effect. We characterized a severely affected infantile-onset female patient whose parents and two siblings exhibited no symptoms of the disease at time of diagnosis. A comprehensive clinical analysis of the proband showed a progressive cerebellar syndrome, including gait ataxia, movement disorders, and saccadic movements, as well as hyperreflexia, visual deterioration, urinary and cardiovascular dysfunction, and impaired nerve conduction. The SCA7 mutation was detected in the proband patient. Subsequently, genetic examination using four ATXN7 gene-linked markers (three centromeric microsatellite markers [D3S1228, D3S1287, and D3S3635] and an intragenic Single Nucleotide Polymorphism [SNP-3145G/A]) revealed that the proband descends from a couple of consanguineous SCA7 mutation carriers. Genotyping analysis demonstrated that all offspring inherited only one mutant allele, and that the severe infantile-onset phenotype is caused by germinal expansion (from 37 to 72 CAG repeats) of the paternal mutant allele. Interestingly, the couple also referred a miscarriage. Finally, we found no CAA interruptions in the ATXN7 gene CAG repeats tract in this family, which might explain, at least in part, the triplet instability in the proband. PMID:25664129

Inbreeding coefficients and degree of consanguineous marriages in Spain: a review.

PubMed

Fuster, Vicente; Colantonio, Sonia Edith

2003-01-01

The contribution of consanguineous marriages corresponding to uncle-niece or aunt-nephew (C12), first cousin (C22), first cousin once removed (C23), and second cousin (C33) to the inbreeding coefficient (alpha) was analyzed from a sample of Spanish areas and periods. Multiple regressions were performed taking as independent variables the different degrees of consanguinity previously selected (C12, C22, C23, and C33) and as dependent variable the inbreeding coefficient (alpha). According to the results obtained for any degree and period, rural frequencies always surpass urban. However, the pattern is similar in both areas. In the period where consanguinity was more elevated (1890-1929) the C22/C33 ratio increased. Its variation is not due to C22 and C33 changes in the same way. In rural areas, this ratio surpasses the expected value by a factor of 2-3, but in urban areas it was 7-10 times larger, in some cases due to migration. While in rural Spain the C33 frequency was approximately 1.5 times C22, in cities C22 was 1.5 times C33. The best fit among the various types of consanguineous matings and alpha involves a lineal relationship. Regardless of the number of variables contributing significantly to alpha, C22 matings are always present. Moreover, their standardized (beta) coefficients are the highest. The above indicates that this consanguineous relationship conditions the inbreeding coefficient the most. In the period of greater consanguinity, close relationships, uncle-niece C12, and first cousin once removed (C23) make a significant contribution to alpha. In rural Spain second cousins (C33) always significantly determined alpha; however, in cities the inbreeding variation was mainly due to C12 and C23. Copyright 2003 Wiley-Liss, Inc.

Genetics of consanguineous marriage: Impact and importance of counseling

PubMed Central

Akrami, Seyed Mohammad

2012-01-01

Consanguineous marriage, marriage between close biological kin, especially that between first cousins, is socially favored in some parts of North Africa, the Middle East and Asia. An increased rate of congenital anomalies and autosomal recessive disorders are significantly associated with such practice. In such communities, misunderstanding and external attempts to discourage such marriage without proper genetic counseling seem to be inappropriate and unsuccessful. Update in knowledge of clinicians especially pediatricians is the aim of this paper regarding importance and issues behind consanguineous marriage. PMID:27625826

Inbreeding in Gredos mountain range (Spain): contribution of multiple consanguinity and intervalley variation.

PubMed

Fuster, V; Jiménez, A M; Colantonio, S E

2001-04-01

The present paper examines consanguineous marriages occurring between 1874 and 1975 in three valleys (Tormes, Alberche, and Tiétar) in the Sierra de Gredos mountain range, Avila province, Spain. Information was obtained from parish registers of 42 localities, corresponding to a total of 41,696 weddings. Consanguineous marriages were defined as those up to the third degree of consanguinity (second cousins). From 1874 to 1975 the percentage of related mates was 4.45% and the inbreeding coefficient was 0.0011868 (for 1874 to 1917 corresponding figures up to the fourth degree were 16.44% and 0.00 19085, respectively). In order to ascertain the characteristics and evolution of mating patterns in Gredos, the contribution of each degree of kinship was analyzed as a whole and then for each valley separately. Regarding total consanguineous marriages in Gredos, there is a low frequency of uncle-niece matings (0.21%) and a first-second cousin mating ratio (C22/C33) of 0.23 (up to the third degree of consanguinity). Before 1918 multiple matings (i.e., those involving more than a single relationship) accounted for 19.16% of consanguineous marriages (up to the fourth degree). The observed frequencies of multiple consanguineous marriages was, on average, about twice that expected at random, and the proportion of such marriages to total inbreeding was 34.65%. The temporal change of the Gredos inbreeding pattern was characterized by a recent decrease; the highest inbreeding levels correspond to the period from 1915 to 1944. Finally, intervalley differences (maximum inbreeding coefficient in the Tormes, minimum in the Tiétar) are interpreted considering the geography, population size, and population mobility for each valley

Tuberous sclerosis complex: neonatal deaths in three of four children of consanguineous, non-expressing parents.

PubMed Central

Ruggieri, M; Carbonara, C; Magro, G; Migone, N; Grasso, S; Tinè, A; Pavone, L; Gomez, M R

1997-01-01

We describe here four sibs, born to consanguineous, healthy, asymptomatic parents. Three of these infants had a rapidly fatal course in the neonatal period; death was attributed to congestive heart failure with radiographic evidence of cardiomegaly in all of them. Necropsy was done in only one of them and showed the typical findings of tuberous sclerosis complex (TSC) in the central nervous system (CNS), kidneys, heart, and liver. The fourth sib, currently 2 years old, also has typical signs of TSC, namely hypomelanotic skin macules and calcified subependymal nodules. Both parents and a living maternal grandmother had appropriate examination, which included skin inspection under Wood's lamp, dental examination, fundoscopy, echocardiography, abdominal and renal ultrasound, and head CT and MRI scans, and no signs of TSC were found in either parent or in the only living grandmother. By history alone there is no other relative with signs or symptoms suggestive of TSC. Linkage analysis and loss of heterozygosity (LOH) investigations on a variety of lesions obtained from postmortem and tissue or blood specimens from all available family members studied failed to identify a microdeletion in the chromosomal regions where TSC genes are located. It is very unusual that in a single TSC family there were three consecutive neonatal deaths, and very likely that all had cardiac rhabdomyomas. Moreover, to the best of our knowledge, there are no previous reports of TSC families with more than one affected sib, unusually severe manifestations of the disease, and completely normal, consanguineous parents. Images PMID:9132502

Genealogical and molecular analysis of a family-based cohort of congenital heart disease patients from the São Miguel Island (Azores, Portugal).

PubMed

Cabral, Rita; Pires, Renato; Anjos, Rui; Branco, Claudia C; Maciel, Paula; Mota-Vieira, Luisa

2016-11-01

Congenital heart disease (CHD) is one common birth malformation, accounting for ∼30% of total congenital abnormalities. Considering the unknown role of consanguinity in causing CHD, this study hypothesised that consanguineous unions and/or familial aggregation may be frequent in the Azorean Island of São Miguel (Portugal). To that end, a retrospective observational study was performed based on genealogical and molecular analyses. The study enrolled 112 CHD patients from São Miguel Island, which allowed the assessment of type of family (simplex or multiplex), parental consanguinity and grandparental endogamy. Based on 15 STR markers, inbreeding coefficients (F IS ) in the CHD cohort and healthy control group (n = 114) were estimated. Multiplex families were 37.6% (n = 41/109), a rate considerably higher than previously described in the literature (< 15%). Moreover, 9.2% (n = 10/109) of the CHD families were consanguineous, mostly derived from third cousin unions, and 20.2% (n = 22/109) presented full grandparental endogamy. Higher F IS values were found in patients with parental consanguinity (0.0371) and patent ductus arteriosus (0.0277). This study analysed several genealogical and genetic features related with CHD, revealing the presence of parental consanguinity and extensive familial aggregation in the CHD patients from São Miguel Island.

Novel SIL1 nonstop mutation in a Chinese consanguineous family with Marinesco-Sjögren syndrome and Dandy-Walker syndrome.

PubMed

Gai, Nan; Jiang, Chen; Zou, Yong-Yi; Zheng, Yu; Liang, De-Sheng; Wu, Ling-Qian

2016-07-01

Marinesco-Sjögren syndrome (MSS) is a rare autosomal recessive disorder, which is characterized by congenital cataracts, cerebellar ataxia, progressive muscle weakness, and delayed psychomotor development. SIL1, which is located at 5q31.2, is the only gene known to cause MSS. Dandy-Walker syndrome (DWS) is defined by hypoplasia, upward rotation of the cerebellar vermis, and cystic dilation of the fourth ventricle; however, its genetic pathogeny remains unclear. Here, we report a Chinese consanguineous family with MSS and DWS. Whole exome sequencing identified a novel nonstop mutation in SIL1. Sanger sequencing revealed that the mutation was segregated in this family according to a recessive mode of inheritance. We found that the mutation changed a stop codon (TGA) to an arginine codon (CGA), and no in-frame termination codon in the 3' untranslated region (UTR) of SIL1 could be found. The mRNA levels of SIL1 were decreased by 56.6% and 37.5% in immortalized lymphoblasts of the patients respectively; the protein levels of SIL1 were substantially decreased. This case study is the first report on Chinese MSS patients, MSS complicated by DWS, and a nonstop mutation in SIL1. Our findings imply the pathogenetic association between DWS and MSS. Copyright © 2016 Elsevier B.V. All rights reserved.

Prevalence of hereditary cancer susceptibility syndromes in children with cancer in a highly consanguineous population.

PubMed

Jastaniah, Wasil; Aljefri, Abdullah; Ayas, Mouhab; Alharbi, Musa; Alkhayat, Nawaf; Al-Anzi, Faisal; Yassin, Fawwaz; Alkasim, Fawaz; Alharbi, Qasim; Abdullah, Shaker; Abrar, Mohammed Burhan; Alsultan, Abdulrahman

2018-05-30

Hereditary cancer susceptibility syndromes (HCSS) are reported in up to one-third of children with cancer. Diagnosis of HCSS is crucial for implementation of surveillance protocols. We identified children who fulfilled criteria for HCSS in Saudi Arabia using the American College of Medical Genetics and Genomics (ACMG) guidelines, addressing the utility of these guidelines in a highly consanguineous population. This multi-center cross-sectional study recruited 1858 children with cancer between January 2011 and December 2014. HCSS criteria were based on the ACMG guidelines. Seven hundred and four (40.4%) out of 1742 eligible patients fulfilled criteria for HCSS. Consanguinity was reported in 629 (38%) patients, with 50 (2.9%) first-degree, 535 (30.7%) second-degree, and 272 (15.6%) third-degree relatives affected with cancer. Two hundred and eighty eight (17.4%) leukemia and 87 (5.3%) brain tumour patients fulfilled HCSS criteria, with parental consanguinity being the most frequent criterion in both (leukemia 85.4%, brain tumors 83.9%). However, leukemia was less frequent in patients of consanguineous parents (p = 0.023). Four out of 10 children with cancer fulfilled criteria for HCSS, most often due to consanguinity. This higher than expected prevalence suggests the need to validate consanguinity as a criterion for HCSS in highly consanguineous populations. Copyright © 2018 Elsevier Ltd. All rights reserved.

Survey of familial glaucoma shows a high incidence of cytochrome P450, family 1, subfamily B, polypeptide 1 (CYP1B1) mutations in non-consanguineous congenital forms in a Spanish population

PubMed Central

Millá, Elena; Mañé, Begoña; Duch, Susana; Hernan, Imma; Borràs, Emma; Planas, Ester; Dias, Miguel de Sousa; Carballo, Miguel

2013-01-01

Purpose To identify myocilin (MYOC) and cytochrome P450, family 1, subfamily B, polypeptide 1 (CYP1B1) mutations in a Spanish population with different clinical forms of familial glaucoma or ocular hypertension (OHT). Methods Index patients from 226 families participated in this study. Patients were diagnosed with familial glaucoma or OHT by complete ophthalmologic examination. Screening for MYOC mutations was performed in 207 index patients: 96 with adult-onset primary open-angle glaucoma (POAG), 21 with primary congenital glaucoma (PCG), 18 with juvenile-onset open-angle glaucoma (JOAG), five with Axenfeld-Rieger syndrome (ARS), and 67 with other types of glaucoma. One hundred two of the families (including all those in whom a MYOC mutation was detected) were also screened for CYP1B1 mutations: 45 POAG, 25 PCG, 21 JOAG, four ARS, and seven others. Results We examined 292 individuals (patients and relatives) with a positive family history of glaucoma or OHT. We identified two novel MYOC variants, p.Lys39Arg and p.Glu218Lys, in two families with POAG, and six previously reported MYOC mutations in seven families with POAG (four), JOAG (one), PCG (one), and normotensive glaucoma (one). CYP1B1 mutations were found in 16 index patients with PCG (nine), POAG (three), JOAG (two), and ARS (two). Conclusions The high percentage (9/25=36%) of mutations in CYP1B1 found in non-consanguineous patients with congenital glaucoma mandates genetic testing. However, the percentage of mutations (9/207=4.4%) in MYOC associated with glaucoma is relatively low in our population. The variable phenotype expression of glaucoma, even in families, cannot be explained with a digenic mechanism between MYOC and CYP1B1. PMID:23922489

Consanguineous marriage in an urban area of Saudi Arabia: rates and adverse health effects on the offspring.

PubMed

al-Abdulkareem, A A; Ballal, S G

1998-02-01

The objective of this cross-sectional study was to determine the pattern and time trend of consanguineous marriage and its adverse health effects on the offspring in Dammam city, Eastern Province, in the Kingdom of Saudi Arabia. This city is known to attract Saudis from different parts of the country because it is in the heart of this industrial region. Five primary health care centers were randomly selected from different sectors of the city in addition to the city's only Maternity and Children's Hospital. For inclusion in the study a wife must have at least one pregnancy that terminated in either full term liveborn baby, still birth, or abortion. A total of 1307 ever-married Saudis completed a pre-structured questionnaire during an interview. The rate of consanguineous marriage was 52.0% with an average inbreeding coefficient of 0.0312. First-cousin marriages were the commonest (39.3%) of all matings. The consanguineous groups had a significantly higher number of pregnancies. The mean birth weight of the offspring of consanguineous couples was not statistically significant being less than that of the non-consanguineous. However, within the consanguineous groups the more closely related couples had smaller babies on average. No significant differences were noted for the rates of inherited diseases and reproductive wastage. The rate of consanguineous marriage in this city was high and so was the inbreeding coefficient. These figures place this nation among the countries with a high rate of consanguineous marriages. A nationwide study to determine accurately the relationship between consanguinity and inherited diseases has much to commend it.

Ignoring Intermarker Linkage Disequilibrium Induces False-Positive Evidence of Linkage for Consanguineous Pedigrees when Genotype Data Is Missing for Any Pedigree Member

PubMed Central

Li, Bingshan; Leal, Suzanne M.

2008-01-01

Missing genotype data can increase false-positive evidence for linkage when either parametric or nonparametric analysis is carried out ignoring intermarker linkage disequilibrium (LD). Previously it was demonstrated by Huang et al. [1] that no bias occurs in this situation for affected sib-pairs with unrelated parents when either both parents are genotyped or genotype data is available for two additional unaffected siblings when parental genotypes are missing. However, this is not the case for autosomal recessive consanguineous pedigrees, where missing genotype data for any pedigree member within a consanguinity loop can increase false-positive evidence of linkage. False-positive evidence for linkage is further increased when cryptic consanguinity is present. The amount of false-positive evidence for linkage, and which family members aid in its reduction, is highly dependent on which family members are genotyped. When parental genotype data is available, the false-positive evidence for linkage is usually not as strong as when parental genotype data is unavailable. For a pedigree with an affected proband whose first-cousin parents have been genotyped, further reduction in the false-positive evidence of linkage can be obtained by including genotype data from additional affected siblings of the proband or genotype data from the proband's sibling-grandparents. For the situation, when parental genotypes are unavailable, false-positive evidence for linkage can be reduced by including genotype data from either unaffected siblings of the proband or the proband's married-in-grandparents in the analysis. PMID:18073490

The prevalence and correlates of consanguineous marriages in Yemen: similarities and contrasts with other Arab countries.

PubMed

Jurdi, Rozzet; Saxena, Prem C

2003-01-01

Using data on 9762 women from the 1997 Yemen Demographic and Maternal and Child Health Survey, this paper examines the prevalence and socioeconomic correlates of consanguineous marriages in Yemen. The results indicate that 40% of marriages are consanguineous, over 85% of which are between first cousins. The prevalence of consanguineous marriages appears to have increased over time, particularly for the last marriage cohort. As for socioeconomic correlates, the study confirms the inverse association between consanguineous marriages and women's education and occupation, age at marriage and economic status. However, no statistically significant difference in the prevalence of consanguinity has been found by place of residence and geographical region. Somewhat unexpected results have been obtained by husband's background characteristics, with higher educated men and those working in the modern sector of the economy being more likely to be married to cousins.

Consanguinity in Qatar: knowledge, attitude and practice in a population born between 1946 and 1991.

PubMed

Sandridge, A L; Takeddin, J; Al-Kaabi, E; Frances, Y

2010-01-01

From March 2007 to March 2008 a cross-sectional study was conducted in Qatar to estimate the prevalence of consanguinity among Qataris and to assess their knowledge of the risks and their attitudes towards the practice. A secondary objective was to test the acceptability of sixteen Likert-style questions within the Qatari population. Face-to-face interviews using a 70-item structured questionnaire were conducted by three native Arabic-speaking medical students with 362 Qatari employees. Where consanguinity existed between the employee's parents, a diagram of the consanguinal relationship (phylogram) was completed. The response rate was 93%. By phylogram, 22% of participants reported a cousin relationship between their parents (consanguinal relationship) and another 15% reported that their parents were from the same tribe (affinal relationship). With respect to their own marital decision, 68% of the respondents had been married at least once. By phylogram, 35% of these reported a consanguineous relationship (first marriage), 9% reported only an affinal relationship and 56% reported that they were not married to a blood relative. Results on the sixteen Likert-style attitude questions were stratified by consanguinity status of parents and of self. In the stratification by consanguinity status of parents the top five attitudes differed by group but there appeared to be more similarity between the consanguinal and only tribal groups. Attitudinal results were stratified by sex. Results showed that the males had a stronger belief in several of the attitudes than females with the exception of causation of genetic abnormalities and health problems. The phylogram was shown to collect more detailed and explicit data than hard-coding. With respect to knowledge, the results showed that knowledge was imperfect with high proportions of participants not knowing that consanguinity has been implicated in autosomal recessive diseases such as thalassaemia, inborn errors of metabolism

In silico analysis of SIGMAR1 variant (rs4879809) segregating in a consanguineous Pakistani family showing amyotrophic lateral sclerosis without frontotemporal lobar dementia.

PubMed

Ullah, Muhammad Ikram; Ahmad, Arsalan; Raza, Syed Irfan; Amar, Ali; Ali, Amjad; Bhatti, Attya; John, Peter; Mohyuddin, Aisha; Ahmad, Wasim; Hassan, Muhammad Jawad

2015-10-01

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. It has been found to be associated with frontotemporal lobar degeneration (FTLD). In the present study, we have described homozygosity mapping and gene sequencing in a consanguineous autosomal recessive Pakistani family showing non-juvenile ALS without signs of FTLD. Gene mapping was carried out in all recruited family members using microsatellite markers, and linkage was established with sigma non-opioid intracellular receptor 1 (SIGMAR1) gene at chromosome 9p13.2. Gene sequencing of SIGMAR1 revealed a novel 3'-UTR nucleotide variation c.672*31A>G (rs4879809) segregating with disease in this family. The C9ORF72 repeat region in intron 1, previously implicated in a related phenotype, was excluded through linkage, and further confirmation of exclusion was obtained by amplifying intron 1 of C9ORF72 with multiple primers in affected individuals and controls. In silico analysis was carried out to explore the possible role of 3'-UTR variant of SIGMAR1 in ALS. The Regulatory RNA motif and Element Finder program revealed disturbance in miRNA (hsa-miR-1205) binding site due to this variation. ESEFinder analysis showed new SRSF1 and SRSF1-IgM-BRCA1 binding sites with significant scores due to this variation. Our results indicate that the 3'-UTR SIGMAR1 variant c.672*31A>G may have a role in the pathogenesis of ALS in this family.

Potential role of gender specific effect of leptin receptor deficiency in an extended consanguineous family with severe early-onset obesity.

PubMed

Dehghani, Mohammad Reza; Mehrjardi, Mohammad Yahya Vahidi; Dilaver, Nafi; Tajamolian, Masoud; Enayati, Samaneh; Ebrahimi, Pirooz; Amoli, Mahsa M; Farooqi, Sadaf; Maroofian, Reza

2018-03-12

Congenital Leptin receptor (LEPR) deficiency is a rare genetic cause of early-onset morbid obesity characterised by severe early onset obesity, major hyperphagia, hypogonadotropic hypogonadism and immune and neuroendocrine/metabolic dysfunction. We identified a homozygous loss-of-function mutation, NM_002303.5:c.464 T > G; p.(Tyr155*), in the LEPR in an extended consanguineous family with multiple individuals affected by early-onset severe obesity and hyperphagia. Interestingly, the LEPR-deficient adult females have extremely high body mass index (BMI) with hypogonadal infertility, the BMI of the affected males began to decline around the onset of puberty (13-15 years) with fertility being preserved. These findings lead to the speculation that LEPR deficiency may have a gender-specific effect on the regulation of body weight. In order to elucidate gender-specific effects of LEPR deficiency on reproduction further investigations are needed. The limitations of this study are that our conclusion is based on observations of two males and two females. Further LEPR deficient males and females are required for comparison in order to support this finding more confidently. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

A prospective study of hepatitis B virus markers in patients with chronic HBV infection from Brazilian families of Western and Asian origin.

PubMed

Carrilho, F J; Ono-Nita, S K; Cardoso, R A; Cancado, E L R; Pinho, J R R; Alves, V A F; Da Silva, L C

2005-09-01

The purpose of the present study was to determine the frequency of hepatitis B virus (HBV) markers in families of HBsAg-positive patients with chronic liver disease. Serum anti-HBc, HBsAg and anti-HBs were determined by enzyme immunoassay and four subpopulations were considered: genetically related (consanguineous) and non-genetically related (non-consanguineous) Asian subjects and genetically related and non-genetically related Western subjects. A total of 165 and 186 relatives of Asian and Western origin were enrolled, respectively. The occurrence of HBsAg and anti-HBs antibodies was significantly higher (P < 0.0001) in family members of Asian origin (81.8%) than in family members of Western origin (36.5%). HBsAg was also more frequent among brothers (79.6 vs 8.5%; P < 0.0001), children (37.9 vs 3.3%; P < 0.0001) and other family members (33.9 vs 16.7%; P < 0.0007) of Asian than Western origin, respectively. No difference between groups was found for anti-HBs, which was more frequently observed in fathers, spouses and other non-genetic relatives. HBV infection was significantly higher in children of Asian than Western mothers (P < 0.0004). In both ethnic groups, the mothers contributed more to their children's infection than the fathers (P < 0.0001). Furthermore, HBsAg was more frequent among consanguineous members and anti-HBs among non-consanguineous members. These results suggest the occurrence of vertical transmission of HBV among consanguineous members and probably horizontal sexual transmission among non-consanguineous members of a family cluster. Thus, the high occurrence of dissemination of HBV infection characterizes family members as a high-risk group that calls for immunoprophylaxis. Finally, the study showed a high familial aggregation rate for both ethnic groups, 18/19 (94.7%) and 23/26 (88.5%) of the Asian and Western origin, respectively.

Do consanguineous parents of a child affected by an autosomal recessive disease have more DNA identical-by-descent than similarly-related parents with healthy offspring? Design of a case-control study

PubMed Central

2010-01-01

Background The offspring of consanguineous relations have an increased risk of congenital/genetic disorders and early mortality. Consanguineous couples and their offspring account for approximately 10% of the global population. The increased risk for congenital/genetic disorders is most marked for autosomal recessive disorders and depends on the degree of relatedness of the parents. For children of first cousins the increased risk is 2-4%. For individual couples, however, the extra risk can vary from zero to 25% or higher, with only a minority of these couples having an increased risk of at least 25%. It is currently not possible to differentiate between high-and low-risk couples. The quantity of DNA identical-by-descent between couples with the same degree of relatedness shows a remarkable variation. Here we hypothesize that consanguineous partners with children affected by an autosomal recessive disease have more DNA identical-by-descent than similarly-related partners who have only healthy children. The aim of the study is thus to establish whether the amount of DNA identical-by-descent in consanguineous parents of children with an autosomal recessive disease is indeed different from its proportion in consanguineous parents who have healthy children only. Methods/Design This project is designed as a case-control study. Cases are defined as consanguineous couples with one or more children with an autosomal recessive disorder and controls as consanguineous couples with at least three healthy children and no affected child. We aim to include 100 case couples and 100 control couples. Control couples are matched by restricting the search to the same family, clan or ethnic origin as the case couple. Genome-wide SNP arrays will be used to test our hypothesis. Discussion This study contains a new approach to risk assessment in consanguineous couples. There is no previous study on the amount of DNA identical-by-descent in consanguineous parents of affected children

Pre-marital genetic counselling to consanguineous couples: attitudes, beliefs and decisions among counselled, noncounselled and unrelated couples in Israel.

PubMed

Shiloh, S; Reznik, H; Bat-Miriam-Katznelson, M; Goldman, B

1995-11-01

Semi-structured interviews were conducted with 65 Israeli subjects who received genetic counselling while considering marriage to a close relative, 40 subjects married to a close relative who did not receive pre-marital genetic counselling, and 125 controls married to a nonrelative and never having considered marrying a relative. It was found that 72% of the consanguineous couples who received pre-marital genetic counselling proceeded with their plans and married their relative; 86% of them reported that the counselling influenced their final decision to some degree. Counsellees' appraisals of genetic counselling revealed unfulfilled expectations to obtain more definitive answers, and mixed reactions to the nondirective approach applied by the counsellors. Comparisons between consanguineous and control couples revealed different views about consanguinity in general, and genetic risks in particular. Consanguineous couples, unlike controls, perceived consanguinity as an ordinary form of marriage, and had more favorable attitudes towards it. Compared to the noncounselled consanguineous group, consanguineous couples who received pre-marital genetic counselling had fewer children, estimated their genetic risk as lower but its subjective significance as higher, and perceived genetic disorders as more severe. The implications of these results are discussed from both theoretical and practical standpoints.

Cervical vertebral fusion (Klippel-Feil) syndrome with consanguineous parents.

PubMed

Juberg, R C; Gershanik, J J

1976-06-01

We describe a female infant with the cervical vertebral fusion (Klippel-Feil) syndrome whom we recognized at birth because of her short neck, restriction of cervical movement, and low posterior hairline. X-ray examination showed anomalies of C1, and between C2-3 and C3-4; thus, we classified her as type II, with variable cervical fusion. At 24 months she was small and manifested hearing deficiency. The mother and father were consanguineous with five common ancestors four generations ago, which resulted in a coefficient of inbreeding equivalent to a second cousin relationship. The parents and grandparents were phenotypically normal, and the parents were radiologically normal. This form of the syndrome has previously been said to be autosomal dominant. Our conclusion of determination by a single autosomal recessive gene is evidence of genetic heterogeneity.

Application of a high-throughput genotyping method for loci exclusion in non-consanguineous Australian pedigrees with autosomal recessive retinitis pigmentosa.

PubMed

Paterson, Rachel L; De Roach, John N; McLaren, Terri L; Hewitt, Alex W; Hoffmann, Ling; Lamey, Tina M

2012-01-01

Retinitis pigmentosa (RP) is the most common form of inherited blindness, caused by progressive degeneration of photoreceptor cells in the retina, and affects approximately 1 in 3,000 people. Over the past decade, significant progress has been made in gene therapy for RP and related diseases, making genetic characterization increasingly important. Recently, high-throughput technologies have provided an option for reasonably fast, cost-effective genetic characterization of autosomal recessive RP (arRP). The current study used a single nucleotide polymorphism (SNP) genotyping method to exclude up to 28 possible disease-causing genes in 31 non-consanguineous Australian families affected by arRP. DNA samples were collected from 59 individuals affected with arRP and 74 unaffected family members from 31 Australian families. Five to six SNPs were genotyped for 28 genes known to cause arRP or the related disease Leber congenital amaurosis (LCA). Cosegregation analyses were used to exclude possible causative genes from each of the 31 families. Bidirectional sequencing was used to identify disease-causing mutations in prioritized genes that were not excluded with cosegregation analyses. Two families were excluded from analysis due to identification of false paternity. An average of 28.9% of genes were excluded per family when only one affected individual was available, in contrast to an average of 71.4% or 89.8% of genes when either two, or three or more affected individuals were analyzed, respectively. A statistically significant relationship between the proportion of genes excluded and the number of affected individuals analyzed was identified using a multivariate regression model (p<0.0001). Subsequent DNA sequencing resulted in identification of the likely disease-causing gene as CRB1 in one family (c.2548 G>A) and USH2A in two families (c.2276 G>T). This study has shown that SNP genotyping cosegregation analysis can be successfully used to refine and expedite the

Challenges in the care for consanguineous couples: an exploratory interview study among general practitioners and midwives

PubMed Central

2012-01-01

Background It is often suggested that an effort must be made to increase awareness among consanguineous couples of their reproductive risk, and to refer them for genetic counseling if needed. Primary care professionals are considered most appropriate for addressing the subject and identifying couples at risk during consultations in their practice. This Dutch study aims to explore the experiences, attitudes and beliefs of such professionals regarding their care for consanguineous couples. Methods Sixteen semi-structured interviews were conducted with midwives and general practitioners. Results Although most primary care professionals considered it their task to inform couples about the risks of consanguinity, during consultations the topic was generally only briefly touched upon and quickly abandoned. Important reasons for this were professionals’ beliefs about religious and social values of couples, their low perception of the couples’ reproductive risk and expected limited feasibility of referral. Feelings of embarrassment regarding addressing consanguinity did not seem to play a significant role. Conclusions Primary care professional beliefs about their clients’ religious and social values, their attitudes toward the risk, and perceived limited options for referral seem to conflict with the professional norm to address the topic of consanguinity. PMID:23102514

An empirical analysis of the effects of consanguineous marriages on economic development.

PubMed

Bildirici, Melike; Kökdener, Meltem; Ersin, Oezgür ömer

2010-01-01

In this study, development experiences toward economic development are investigated to provide an alternative analysis of economic development, human capital, and genetic inheritance in the light of consanguineous marriages. The countries analyzed in the study are discussed in accordance with consanguineous marriage practices and classified by their per capita gross domestic product (GDP) growth. A broad range of countries are analyzed in the study. Arab countries that experienced high rates of growth in their gross national income during the twentieth century but failed to fulfill adequate development measures as reflected in the growth in national income, countries undergoing transition from tight government regulation to free market democracy, and African nations that have experienced complications in the process of development show important differences in the process of economic development. It is shown that the countries that have reached high average development within the context of per capita GDP have overcome problems integral to consanguineous marriage.

Prevalence and characteristics of non-syndromic orofacial clefts and the influence of consanguinity.

PubMed

Alamoudi, N M; Sabbagh, H J; Innes, N P T; El Derwi, D; Hanno, A Z; Al-Aama, J Y; Habiballah, A H; Mossey, P A

2014-01-01

The Objective of this study was to identify the prevalence and describe the characteristics of non-syndromic orofacial cleft (NSOFC) in Jeddah, Saudi Arabia and examine the influence of consanguinity. Six hospitals were selected to represent Jeddah's five municipal districts. New born infants with NSOFC born between 1st of January 2010 to 31st of December 2011 were clinically examined and their number compared to the total number of infants born in these hospitals to calculate the prevalence of NSOFC types and sub-phenotypes. Referred Infants were included for the purpose of studying NSOFC characteristics and their relationship to consanguinity. Information on NSOFC infants was gathered through parents' interviews, infants 'files and patient examinations. Prospective surveillance of births resulted in identifying 37 NSOFC infants born between 1st of January 2010 to 31st of December 2011 giving a birth prevalence of 0.80/1000 living births. The total infants seen, including referred cases, were 79 children. Consanguinity among parents of cleft palate (CP) cases was statistically higher than that among cleft lip with or without cleft palate (CL/P) patients (P = 0.039). Although there appears to be a trend in the relationship between consanguinity and severity of CL/P sub-phenotype, it was not statistically significant (P = 0.248). Birth prevalence of NSOFC in Jeddah City was 0.8/1000 live births with CL/P: 0.68/1000 and CP: 0.13/1000. Both figures were low compared to the global birth prevalence (NSOFC: 1.25/1000, CL/P: 0.94/1000 and CP: 0.31/1000 live births). Consanguineous parents were statistically higher among CP cases than among other NSOFC phenotypes.

Missouri Small Farm Family Program. Revised.

ERIC Educational Resources Information Center

Enlow, George; And Others

Records maintained by rural extension designees on the Missouri Small Farm Family Program, (initiated in 1972 by the cooperative extension service to help low income farm families learn to use available resources to improve their quality of life) provided data re: family characteristics, farm improvement progress, and improvement in the quality of…

Consanguinity and its relationship to differential fertility and mortality in the Kotia: a tribal population of Andhra Pradesh, India.

PubMed

Yasim; Naidu, J M; Mascie-Taylor, C G

1997-04-01

Data on patterns of marriage, differential fertility and mortality were collected from 211 Kotia women residing in Visakhapatnam district of Andhra Pradesh, India. Consanguineous marriages made up just over a quarter of the total, and of these, father's sister's daughter (FSD) were more common than mother's brother's daughter (MBD). The mean inbreeding coefficient for the sample (F) was 0.0172. Women in consanguineous marriages had a lower mean number of total conceptions, live births and living offspring (net fertility) than women in non-consanguineous marriages. Significant heterogeneity was found in the means of living offspring for FSD, MBD and non-consanguineous couples, but not for conceptions and live births.

An insight into recent consanguinity within the Basque area in Spain. Effects of autochthony, industrialization and demographic changes.

PubMed

Alfonso-Sanchez, M A; Peña, J A; Aresti, U; Calderón, R

2001-01-01

The importance of studying the genetic kinship of those human groups characterized by a deeply rooted ethnicity has traditionally been and still is an interesting goal of anthropological and population genetic studies. However, only a few surveys have aimed to learn about the impact of industrial development on the consanguinity of these populations and even those have concentrated on industrialized regions. This approach is worth analysing in Spain, where industrialization was late in relation to other western European countries. In this work we analyse the characteristics of inbreeding in Guipúzcoa from 1951 to 1995. This Basque province underwent industrial and tourist development earlier than other Spanish regions. It has the highest density of Basque speakers and has always occupied a central position within the map of distribution of the Basque language. Guipúzcoa is geographically placed in the core of the Basque area. SUDJECTS AND METHODS: Data on consanguineous marriages recorded in the province of Guipúzcoa between 1951 and 1995 were taken from Roman Catholic dispensations stored in the Diocesan Archives of San Sebastián, the province's capital city. Over the whole time period, a total of 1152 consanguineous marriages were registered. The high frequencies of first cousin (M22) (F = 1/16) and uncle-niece, aunt-nephew (M12) (F = 1/8) consanguineous marriages distinguish Guipúzcoa from the rest of Iberian populations. The M22/M33 ratio (with M33 being second cousins) has never dropped below 0.67, which represents a significant deviation from the expectation value of 0.25. When consanguineous marriages are classified according to marriage partner birthplaces interesting results emerge. Provincial endogamy shows the highest consanguinity rates (57%) and the proportion of M22/M33 is also rather high (0.63). However, a major contribution to the consanguinity levels and mean inbreeding coefficient recorded in Guipúzcoa over recent decades has been made by

The Effect of Consanguineous Marriage on Mental Health among the Students of the Shahrekord University of Medical Sciences

PubMed Central

Hosseinpour, Maryam; Deris, Fatemeh; Solati-Dehkordi, Kamal; Heidari-Soreshjani, Sheida; Karimi, Negar; Teimori, Hossein

2016-01-01

Introduction In Iran, after unintentional accidents, mental health problems are the second leading burden of disease. Consanguineous marriage is very common in Iran and the association between parental consanguinity and mental health is an important issue that has not yet been studied sufficiently in Iran. Aim To investigate the effect of consanguinity and the degree of relationship on different levels of mental health. Materials and Methods In this cross-sectional study, conducted in the Shahrekord University of Medical Sciences, two groups of students were enrolled. The first group consisted of 156 students that had consanguineous parent (case group) and the second group was 156 students whose parents had non-blood relationship (control group). The students were evaluated using General Health Questionnaire (GHQ-28). Statistical analysis was conducted by Pearson’s correlation coefficient, independent t-test and the one-way analysis of variance. Odd ratio was used to estimate the relative risk. Results Over 30% of the individuals were suffering from mental health problems. The most and least common mental health problems in both groups were social dysfunction (54.5% in the case group and the control group 50%) and depression (15.4% in the case group and 17.3% in the control group), respectively. No statistically significant difference was observed in the frequency of overall mental health and its subscales between student with non-consanguineous parent (control group) and the students that had consanguineous parent (case group) (p>0.05) and the status of mental health was not significantly different among student with different degree of kinship (p>0.05). Conclusion The study revealed that social dysfunction was very common among the study students and also there were no relationship between parental consanguineous marriage and mental health. Parental consanguinity and genetic factors may not be the major causes of high prevalence of mental health problems in

The Effect of Consanguineous Marriage on Mental Health among the Students of the Shahrekord University of Medical Sciences.

PubMed

Hosseinpour, Maryam; Deris, Fatemeh; Solati-Dehkordi, Kamal; Heidari-Soreshjani, Sheida; Karimi, Negar; Teimori, Hossein

2016-11-01

In Iran, after unintentional accidents, mental health problems are the second leading burden of disease. Consanguineous marriage is very common in Iran and the association between parental consanguinity and mental health is an important issue that has not yet been studied sufficiently in Iran. To investigate the effect of consanguinity and the degree of relationship on different levels of mental health. In this cross-sectional study, conducted in the Shahrekord University of Medical Sciences, two groups of students were enrolled. The first group consisted of 156 students that had consanguineous parent (case group) and the second group was 156 students whose parents had non-blood relationship (control group). The students were evaluated using General Health Questionnaire (GHQ-28). Statistical analysis was conducted by Pearson's correlation coefficient, independent t-test and the one-way analysis of variance. Odd ratio was used to estimate the relative risk. Over 30% of the individuals were suffering from mental health problems. The most and least common mental health problems in both groups were social dysfunction (54.5% in the case group and the control group 50%) and depression (15.4% in the case group and 17.3% in the control group), respectively. No statistically significant difference was observed in the frequency of overall mental health and its subscales between student with non-consanguineous parent (control group) and the students that had consanguineous parent (case group) (p>0.05) and the status of mental health was not significantly different among student with different degree of kinship (p>0.05). The study revealed that social dysfunction was very common among the study students and also there were no relationship between parental consanguineous marriage and mental health. Parental consanguinity and genetic factors may not be the major causes of high prevalence of mental health problems in Iran and the effects of the environmental factors on these

A novel loss-of-function mutation in GPR54/KISS1R leads to hypogonadotropic hypogonadism in a highly consanguineous family.

PubMed

Nimri, Revital; Lebenthal, Yael; Lazar, Liora; Chevrier, Lucie; Phillip, Moshe; Bar, Meytal; Hernandez-Mora, Eva; de Roux, Nicolas; Gat-Yablonski, Galia

2011-03-01

The G protein-coupled receptor 54 (GPR54), the kisspeptin receptor, is essential for stimulation of GnRH secretion and induction of puberty. Recently loss-of-function mutations of the GPR54 have been implicated as a cause of isolated idiopathic hypogonadotropic hypogonadism (IHH). The objective of the study was to identify the genetic cause of IHH in a consanguineous pedigree and to characterize the phenotypic features from infancy through early adulthood. In six patients with normosmic IHH belonging to two families of Israeli Muslim-Arab origin highly related to one another, DNA was analyzed for mutations in the GnRHR and GPR54 genes, with functional analysis of the mutation found. The five males underwent comprehensive endocrine evaluation and were under longitudinal follow-up; the one female presented in early adulthood. A new homozygous mutation (c.T815C) in GPR54 leading to a phenylalanine substitution by serine (p.F272S) was detected in all patients. Functional analysis showed an almost complete inhibition of kisspeptin-induced GPR54 signaling and a dramatic decrease of the mutated receptor expression at the cell surface. The males exhibited the same clinical features from infancy to adulthood, characterized by cryptorchidism, a relatively short penis, and no spontaneous pubertal development. The female patient presented at 18 yr with impuberism and primary amenorrhea. Repeated stimulation tests demonstrated complete gonadotropin deficiency throughout follow-up. A novel loss-of-function mutation (p.F272S) in the GPR54 gene is associated with familial normosmic IHH. Underdeveloped external genitalia and impuberism point to the major role of GPR54 in the activation of the gonadotropic axis from intrauterine life to adulthood.

Application of a high-throughput genotyping method for loci exclusion in non-consanguineous Australian pedigrees with autosomal recessive retinitis pigmentosa

PubMed Central

Paterson, Rachel L.; McLaren, Terri L.; Hewitt, Alex W.; Hoffmann, Ling; Lamey, Tina M.

2012-01-01

Purpose Retinitis pigmentosa (RP) is the most common form of inherited blindness, caused by progressive degeneration of photoreceptor cells in the retina, and affects approximately 1 in 3,000 people. Over the past decade, significant progress has been made in gene therapy for RP and related diseases, making genetic characterization increasingly important. Recently, high-throughput technologies have provided an option for reasonably fast, cost-effective genetic characterization of autosomal recessive RP (arRP). The current study used a single nucleotide polymorphism (SNP) genotyping method to exclude up to 28 possible disease-causing genes in 31 non-consanguineous Australian families affected by arRP. Methods DNA samples were collected from 59 individuals affected with arRP and 74 unaffected family members from 31 Australian families. Five to six SNPs were genotyped for 28 genes known to cause arRP or the related disease Leber congenital amaurosis (LCA). Cosegregation analyses were used to exclude possible causative genes from each of the 31 families. Bidirectional sequencing was used to identify disease-causing mutations in prioritized genes that were not excluded with cosegregation analyses. Results Two families were excluded from analysis due to identification of false paternity. An average of 28.9% of genes were excluded per family when only one affected individual was available, in contrast to an average of 71.4% or 89.8% of genes when either two, or three or more affected individuals were analyzed, respectively. A statistically significant relationship between the proportion of genes excluded and the number of affected individuals analyzed was identified using a multivariate regression model (p<0.0001). Subsequent DNA sequencing resulted in identification of the likely disease-causing gene as CRB1 in one family (c.2548 G>A) and USH2A in two families (c.2276 G>T). Conclusions This study has shown that SNP genotyping cosegregation analysis can be successfully

Amelogenesis Imperfecta: 1 Family, 2 Phenotypes, and 2 Mutated Genes.

PubMed

Prasad, M K; Laouina, S; El Alloussi, M; Dollfus, H; Bloch-Zupan, A

2016-12-01

Amelogenesis imperfecta (AI) is a clinically and genetically heterogeneous group of diseases characterized by enamel defects. The authors have identified a large consanguineous Moroccan family segregating different clinical subtypes of hypoplastic and hypomineralized AI in different individuals within the family. Using targeted next-generation sequencing, the authors identified a novel heterozygous nonsense mutation in COL17A1 (c.1873C>T, p.R625*) segregating with hypoplastic AI and a novel homozygous 8-bp deletion in C4orf26 (c.39_46del, p.Cys14Glyfs*18) segregating with hypomineralized-hypoplastic AI in this family. This study highlights the phenotypic and genotypic heterogeneity of AI that can exist even within a single consanguineous family. Furthermore, the identification of novel mutations in COL17A1 and C4orf26 and their correlation with distinct AI phenotypes can contribute to a better understanding of the pathophysiology of AI and the contribution of these genes to amelogenesis. © International & American Associations for Dental Research 2016.

Dandy-Walker malformation, genitourinary abnormalities, and intellectual disability in two families.

PubMed

Zaki, Maha S; Masri, Amira; Gregor, Anne; Gleeson, Joseph G; Rosti, Rasim Ozgur

2015-11-01

We report on two families, each with documented consanguinity and two affected with overlapping features of Dandy-Walker malformation, genitourinary abnormalities, intellectual disability, and hearing deficit. This phenotype shares similar findings with many well-known syndromes. However, the clinical findings of this syndrome categorize this as a new syndrome as compared with the phenotype of already established syndromes. Due to parental consanguinity, occurrence in siblings of both genders and the absence of manifestations in obligate carrier parents, an autosomal recessive pattern of inheritance is more likely. The authors believe that these families suggest a novel autosomal recessive cerebello-genital syndrome. Array CGH analyses of an affected did not show pathological deletions or duplications. © 2015 Wiley Periodicals, Inc.

Dandy–Walker Malformation, Genitourinary Abnormalities, and Intellectual Disability in Two Families

PubMed Central

Gregor, Anne; Gleeson, Joseph G.; Rosti, Rasim Ozgur

2016-01-01

We report on two families, each with documented consanguinity and two affected with overlapping features of Dandy-Walker malformation, genitourinary abnormalities, intellectual disability, and hearing deficit. This phenotype shares similar findings with many well-known syndromes. However, the clinical findings of this syndrome categorize this as a new syndrome as compared with the phenotype of already established syndromes. Due to parental consanguinity, occurrence in siblings of both genders and the absence of manifestations in obligate carrier parents, an autosomal recessive pattern of inheritance is more likely. The authors believe that these families suggest a novel autosomal recessive cerebello–genital syndrome. Array CGH analyses of an affected did not show pathological deletions or duplications. PMID:26109232

ASSESSMENT OF KNOWLEDGE, ATTITUDE AND PRACTICE TOWARDS CONSANGUINEOUS MARRIAGES AMONG A COHORT OF MULTIETHNIC HEALTH CARE PROVIDERS IN SAUDI ARABIA.

PubMed

Alnaqeb, Dhekra; Hamamy, Hanan; Youssef, Amira M; Al-Rubeaan, Khalid

2018-01-01

This study aimed to assess knowledge, attitude and practice related to consanguinity among multiethnic health care providers in the Kingdom of Saudi Arabia. Using a cross-sectional study design, a validated, self-administered close-ended questionnaire was randomly distributed to health care providers in different health institutions in the country between 1st August 2012 and 31st July 2013. A total of 1235 health care providers completed the study questionnaire. Of the 892 married participants (72.23% of total), 11.43% were married to a first cousin, and were predominantly Arabs, younger than 40 years and male. Only 17.80% of the patients seen by the health care providers requested consanguinity related counselling. A knowledge barrier was expressed by 27.49% of the participants, and 85.67% indicated their willingness to have more training in basic genetic counselling. A language barrier was expressed as a limiting factor to counselling for consanguinity among non-Arabs. The health care providers had a major dearth of knowledge that was reflected in their attitude and practice towards consanguinity counselling. This finding indicates the need for more undergraduate and postgraduate medical and nursing education and training in the counselling of consanguineous couples. It is recommended that consanguinity counselling is included in the current premarital screening and counselling programmes in the Kingdom.

Molecular Genetic Analysis of Pakistani Families With Autosomal Recessive Congenital Cataracts by Homozygosity Screening

PubMed Central

Chen, Jianjun; Wang, Qiwei; Cabrera, Patricia E.; Zhong, Zilin; Sun, Wenmin; Jiao, Xiaodong; Chen, Yabin; Govindarajan, Gowthaman; Naeem, Muhammad Asif; Khan, Shaheen N.; Ali, Muhammad Hassaan; Assir, Muhammad Zaman; Rahman, Fawad Ur; Qazi, Zaheeruddin A.; Riazuddin, Sheikh; Akram, Javed; Riazuddin, S. Amer; Hejtmancik, J. Fielding

2017-01-01

Purpose To identify the genetic origins of autosomal recessive congenital cataracts (arCC) in the Pakistani population. Methods Based on the hypothesis that most arCC patients in consanguineous families in the Punjab areas of Pakistan should be homozygous for causative mutations, affected individuals were screened for homozygosity of nearby highly informative microsatellite markers and then screened for pathogenic mutations by DNA sequencing. A total of 83 unmapped consanguineous families were screened for mutations in 33 known candidate genes. Results Patients in 32 arCC families were homozygous for markers near at least 1 of the 33 known CC genes. Sequencing the included genes revealed homozygous cosegregating sequence changes in 10 families, 2 of which had the same variation. These included five missense, one nonsense, two frame shift, and one splice site mutations, eight of which were novel, in EPHA2, FOXE3, FYCO1, TDRD7, MIP, GALK1, and CRYBA4. Conclusions The above results confirm the usefulness of homozygosity mapping for identifying genetic defects underlying autosomal recessive disorders in consanguineous families. In our ongoing study of arCC in Pakistan, including 83 arCC families that underwent homozygosity mapping, 3 mapped using genome-wide linkage analysis in unpublished data, and 30 previously reported families, mutations were detected in approximately 37.1% (43/116) of all families studied, suggesting that additional genes might be responsible in the remaining families. The most commonly mutated gene was FYCO1 (14%), followed by CRYBB3 (5.2%), GALK1 (3.5%), and EPHA2 (2.6%). This provides the first comprehensive description of the genetic architecture of arCC in the Pakistani population. PMID:28418495

[The point-digital interpretation and the choice of the dermatoglyphic patterns on human fingers for diagnostics of consanguineous relationship].

PubMed

Zvyagin, V N; Rakitin, V A; Fomina, E E

The objective of the present study was the development of the point-digital model for the scaless interpretation of the dermatoglyphic papillary patterns on human fingers that would allow to comprehensively describe, in digital terms, the main characteristics of the traits and perform the quantitative assessment of the frequency of their inheritance. A specially developed computer program, D.glyphic. 7-14 was used to mark the dermatoglyphic patterns on the fingerprints obtained from 30 familial triplets (father + mother + child).The values of all the studied traits for kinship diagnostics were found by calculating the ratios of the sums of differences between the traits in the parent-parent pairs to those in the respective parent-child pairs. The algorithms for the point marking of the traits and reading out the digital information about them have been developed. The traditional dermatoglyphic patterns were selected and the novel ones applied for the use in the framework of the point-digital model for the interpretation of the for diagnostics of consanguineous relationship. The present experimental study has demonstrated the high level of inheritance of the selected traits and the possibility to develop the algorithms and computation techniques for the calculation of consanguineous relationship coefficients based on these traits.

Bernard-Soulier syndrome in two Afrikaner families.

PubMed

Grové, S S; Kromberg, J G

1985-06-29

The hereditary autosomal recessive disorder of platelet function known as the Bernard-Soulier syndrome (B-SS) is described in two Afrikaner families. Consanguinity exists in one of the families, which is descended from Trekboer Afrikaners who migrated from Rustenburg, Transvaal, to Angola in 1876 and then to SWA/Namibia in the 1920s. Since both families have French Huguenot ancestors and since there are 7 confirmed and 5 reported cases of B-SS in these two families, founder effect may be operating and causing this rare disorder to occur more frequently in this population group than would otherwise be expected.

Consanguinity in Saudi Arabia: a unique opportunity for pediatric kidney research.

PubMed

Kari, Jameela A; Bockenhauer, Detlef; Stanescu, Horia; Gari, Mamdooh; Kleta, Robert; Singh, Ajay K

2014-02-01

Identification of disease-related genes is a critical step in understanding the molecular basis of disease and developing targeted therapies. The genetic study of diseases occurring in the offspring of consanguineous unions is a powerful way to discover new disease genes. Pediatric nephrology provides an excellent example because ∼70% of cases of kidney disease in childhood are congenital with a likely genetic basis. This percentage is likely to be even higher in countries with a high consanguinity rate, such as the Kingdom of Saudi Arabia. However, there are a number of challenges, such as cultural, legal, and religious restrictions, that should be appreciated before carrying out genetic research in a tradition-bound country. In this article, we discuss the background, opportunities, and challenges involved with this unique opportunity to conduct studies of such genetic disorders. Keys to success include collaboration and an understanding of local traditions and laws. Copyright © 2014 National Kidney Foundation, Inc. All rights reserved.

CONSANGUINITY, GENETICS AND DEFINITIONS OF KINSHIP IN THE UK PAKISTANI POPULATION.

PubMed

Bittles, A H; Small, N A

2016-11-01

Consanguineous marriage is a controversial topic in many Western societies, with attention mainly focused on the health of immigrant communities from Asia and Africa. In the UK consanguinity is especially prevalent in the Pakistani community, which now numbers over 1.1 million. Less attention has been paid to the influence of hereditary population stratification within Pakistani communities, in particular biraderi (literally brotherhood) membership, which denotes male lineages that largely govern marriage partner choice and hence the transmission of disease genes. The various roles played by biraderi and their relationship to other socio-occupational and kinship terms, such as caste, quom and zat, are often overlooked in health-based studies. The interchangeable use of these different kinship terms without rigorous definition can create identity uncertainty and hinders inter-study comparisons. Where feasible, standardization of terminology would be both desirable and beneficial, with biraderi the preferred default term to identify specific social and genetic relationships within the Pakistani diaspora.

Small Families

MedlinePlus

... Life Family Life Family Life Medical Home Family Dynamics Media Work & Play Getting Involved in Your Community ... Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care Communication & Discipline Types of Families ...

Study of a large Anglo-Saxon family with beta-thalassaemia trait.

PubMed

Raik, E; Powell, E; Gordon, S

1976-01-01

Study of a large Anglo-Saxon family with beta-thalassaemia trait revealed evidence of consanguinity, moreover both branches of the family shared a Spanish ancestor. The manifestations of the disorder were varied in severity and yet the degree of severity appeared to breed true within any individual part of the family. Our explanation for the inheritance pattern observed in the family was to postulate the existence of two non-allelic genes influencing the rate of beta-chain synthesis.

Birth prevalence of non-syndromic orofacial clefts in Saudi Arabia and the effects of parental consanguinity

PubMed Central

Sabbagh, Heba J.; Innes, Nicola P.; Sallout, Bahauddin I.; Alamoudi, Najlaa M.; Hamdan, Mustafa A.; Alhamlan, Nasir; Al-Khozami, Amaal I.; Abdulhameed, Fatma D.; Al-Aama, Jumana Y.; Mossey, Peter A.

2015-01-01

Objectives: To describe the characteristics and prevalence of non-syndromic orofacial clefting (NSOFC) and assess the effects of parental consanguinity on NSOFC phenotypes in the 3 main cities of Saudi Arabia. Methods: All infants (114,035) born at 3 referral centers in Riyadh, and 6 hospitals in Jeddah and Madinah between January 2010 and December 2011 were screened. The NSOFC cases (n=133) were identified and data was collected through clinical examination and records, and information on consanguinity through parent interviews. The diagnosis was confirmed by reviewing medical records and contacting the infants’ pediatricians. Control infants (n=233) matched for gender and born in the same hospitals during the same period, were selected. Results: The prevalence of NSOFC was 1.07/1000 births in Riyadh, and 1.17/1000 births overall; cleft lip (CL) was 0.47/1000 births, cleft lip and palate (CLP) was 0.42/1000 births, and cleft palate (CP) was 0.28/1000 births. Cleft palate was significantly associated with consanguinity (p=0.047, odds ratio: 2.5, 95% confidence interval: 1 to 6.46), particularly for first cousin marriages. Conclusion: The birth prevalence of NSOFC in Riyadh alone, and in the 3 main cities of Saudi Arabia were marginally lower than the mean global prevalence. While birth prevalence for CLP was comparable to global figures, the CL:CLP ratio was high, and only CP was significantly associated with consanguinity. PMID:26318465

Consanguineous marriage and increased risk of idiopathic congenital talipes equinovarus: a case-control study in a rural area.

PubMed

Sahin, Orcun; Yildirim, Cengiz; Akgun, Rahmi C; Haberal, Bahtiyar; Yazici, Ayse C; Tuncay, Ismail C

2013-01-01

The purpose of this study is to evaluate if there is any relationship between consanguineous marriages and idiopathic congenital talipes equinovarus (CTEV). A case-control study on CTEV screening was conducted in a rural eastern city of Turkey between 2009 and 2011 and a total of 28 cases (infants with idiopathic CTEV) and 575 controls (healthy infants) were recruited. Sociodemographic status of the infants, including gestational age and birth weights, maternal characteristics and, if any, the degree of consanguinity, were recorded. As an inclusion criterion, only singleton, full-term, live births were accepted. A backward stepwise logistic regression model was used to evaluate the relationship between idiopathic CTEV and parental consanguinity. Unadjusted and adjusted odds ratios (OR) with 95% confidence interval (CI) were calculated. Among maternal and infant characteristics, significant risk factors for idiopathic CTEV in the regression analysis were work status (employed), consanguineous marriage, sex (male), and gestational age (>42 wk). Babies born to first-cousin parents had >4 times the risk of idiopathic CTEV [OR, 4.138, (95% CI, 1.484, 11.538)] and the risk for those born to distant relatives was 2.9 times higher [OR, 2.941, (95% CI, 1.070, 8.087)] than for children of unrelated parents. Consanguineous marriage was significantly associated with an increased risk of idiopathic CTEV. This association remained significant even after adjusting for potential confounding variables. To obtain more accurate results, a population-based screening study with an increased number of cases and controls should be performed in future studies. Case-control study investigating the effect of a patient characteristic on the outcome of disease (level-III).

Does anonymous sperm donation increase the risk for unions between relatives and the incidence of autosomal recessive diseases due to consanguinity?

PubMed

Serre, Jean-Louis; Leutenegger, Anne-Louise; Bernheim, Alain; Fellous, Marc; Rouen, Alexandre; Siffroi, Jean-Pierre

2014-03-01

In France gamete donation and notably sperm donation are anonymous. It has been claimed that anonymous artificial insemination by donor (AID) could highly contribute to an increase in the level of consanguinity and the incidence of autosomal recessive diseases, due to the unions between offspring of anonymous donors, unaware of their biological kinship, with the special case of unions between half-siblings. The actual incidence of consanguinity due to AID was compared with that resulting from the two other main sources of consanguinity and recessive diseases, i.e. voluntary unions between related individuals or inadvertent unions between the offspring of a common unknown male ancestor (false paternity). From these data, we estimated that expected unions in France between half sibs per year are 0.12 between offspring of sperm donors (1.2 every 10 years) and 0.5 between offspring of common male ancestors through false paternity (5 every 10 years). More generally, the inadvertent unions between false paternity offspring are roughly four times more frequent than those resulting from anonymous AID. We estimated that in the future, when AID has been in practice for several generations, out the 820 000 annual births in France, respectively, 6 and 25 births will be consanguineous through an unknown common ancestor related to anonymous AID and to a false paternity, both of which are negligible when compared with the 1256 children born from first-degree cousins. About 672 children per year are born with a recessive genetic disease due to the panmictic risk and additional affected cases due to consanguinity would be 34.54 for first-cousin offspring, 0.33 for offspring of individuals related due to false paternity and 0.079 for offspring of individuals related due to anonymous AID. Anonymous AID would therefore be responsible for 0.46% of consanguineous births and for 0.01% of recessive diseases. Therefore, the effect of anonymous AID on half-sibling unions, consanguinity and

Whole-exome sequencing identifies novel homozygous mutation in NPAS2 in family with nonobstructive azoospermia.

PubMed

Ramasamy, Ranjith; Bakırcıoğlu, M Emre; Cengiz, Cenk; Karaca, Ender; Scovell, Jason; Jhangiani, Shalini N; Akdemir, Zeynep C; Bainbridge, Matthew; Yu, Yao; Huff, Chad; Gibbs, Richard A; Lupski, James R; Lamb, Dolores J

2015-08-01

To investigate the genetic cause of nonobstructive azoospermia (NOA) in a consanguineous Turkish family through homozygosity mapping followed by targeted exon/whole-exome sequencing to identify genetic variations. Whole-exome sequencing (WES). Research laboratory. Two siblings in a consanguineous family with NOA. Validating all variants passing filter criteria with Sanger sequencing to confirm familial segregation and absence in the control population. Discovery of a mutation that could potentially cause NOA. A novel nonsynonymous mutation in the neuronal PAS-2 domain (NPAS2) was identified in a consanguineous family from Turkey. This mutation in exon 14 (chr2: 101592000 C>G) of NPAS2 is likely a disease-causing mutation as it is predicted to be damaging, it is a novel variant, and it segregates with the disease. Family segregation of the variants showed the presence of the homozygous mutation in the three brothers with NOA and a heterozygous mutation in the mother as well as one brother and one sister who were both fertile. The mutation is not found in the single-nucleotide polymorphism database, the 1000 Genomes Project, the Baylor College of Medicine cohort of 500 Turkish patients (not a population-specific polymorphism), or the matching 50 fertile controls. With the use of WES we identified a novel homozygous mutation in NPAS2 as a likely disease-causing variant in a Turkish family diagnosed with NOA. Our data reinforce the clinical role of WES in the molecular diagnosis of highly heterogeneous genetic diseases for which conventional genetic approaches have previously failed to find a molecular diagnosis. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Associations of recurrent miscarriages with chromosomal abnormalities, thrombophilia allelic polymorphisms and/or consanguinity in Saudi Arabia.

PubMed

Turki, Rola F; Assidi, Mourad; Banni, Huda A; Zahed, Hanan A; Karim, Sajjad; Schulten, Hans-Juergen; Abu-Elmagd, Muhammad; Rouzi, Abdulrahim A; Bajouh, Osama; Jamal, Hassan S; Al-Qahtani, Mohammed H; Abuzenadah, Adel M

2016-10-10

Recurrent pregnancy loss (RPL) or recurrent spontaneous abortion is an obstetric complication that affects couples at reproductive age. Previous reports documented a clear relationship between parents with chromosomal abnormalities and both recurrent miscarriages and infertility. However, limited data is available from the Arabian Peninsula which is known by higher rates of consanguineous marriages. The main goal of this study was to determine the prevalence of chromosomal abnormalities and thrombophilic polymorphisms, and to correlate them with RPL and consanguinity in Saudi Arabia. Cytogenetic analysis of 171 consent patients with RPL was performed by the standard method of 72-h lymphocyte culture and GTG banding. Allelic polymorphisms of three thrombophilic genes (Factor V Leiden, Prothrombin A20210G, MTHFR C677T) were performed using PCR-RFLP (restriction fragment length polymorphism) and gel electrophoresis. Data analysis revealed that 7.6 % of patients were carrier of numerical or structural chromosomal abnormalities. A high rate of translocations (46 %) was associated to increased incidence of RPL. A significant correlation between consanguineous RPL patients and chromosomal abnormalities (P < 0.05) was found. Both Factor V Leiden and Prothrombin A20210G allelic polymorphisms were significantly associated with a higher prevalence of RPL. This study demonstrated a strong association between RPL and the prevalence of chromosomal abnormalities and inherited thrombophilia. Given the high rate of consanguineous marriages in the Saudi population, these results underline the importance of systematic cytogenetic investigation and genetic counseling preferably at the premarital stage or at least during early pregnancy phase through preimplantation genetic diagnosis (PGD).

Institutional Protocol to Manage Consanguinity Detected by Genetic Testing in Pregnancy in a Minor

PubMed Central

Chen, Laura P.; Beck, Anita E.; Tsuchiya, Karen D.; Chow, Penny M.; Mirzaa, Ghayda M.; Wiester, Rebecca T.

2015-01-01

Single-nucleotide polymorphism arrays and other types of genetic tests have the potential to detect first-degree consanguinity and uncover parental rape in cases of minor teenage pregnancy. We present 2 cases in which genetic testing identified parental rape of a minor teenager. In case 1, single-nucleotide polymorphism array in a patient with multiple developmental abnormalities demonstrated multiple long stretches of homozygosity, revealing parental rape of a teenage mother. In case 2, a vague maternal sexual assault history and diagnosis of Pompe disease by direct gene sequencing identified parental rape of a minor. Given the medical, legal, and ethical implications of such revelations, a protocol was developed at our institution to manage consanguinity identified via genetic testing. PMID:25687148

Family relationship, water contact and occurrence of Buruli ulcer in Benin.

PubMed

Sopoh, Ghislain Emmanuel; Barogui, Yves Thierry; Johnson, Roch Christian; Dossou, Ange Dodji; Makoutodé, Michel; Anagonou, Sévérin Y; Kestens, Luc; Portaels, Françoise

2010-07-13

Mycobacterium ulcerans disease (Buruli ulcer) is the most widespread mycobacterial disease in the world after leprosy and tuberculosis. How M. ulcerans is introduced into the skin of humans remains unclear, but it appears that individuals living in the same environment may have different susceptibilities. This study aims to determine whether frequent contacts with natural water sources, family relationship or the practice of consanguineous marriages are associated with the occurrence of Buruli ulcer (BU). Case control study. Department of Atlantique, Benin. BU-confirmed cases that were diagnosed and followed up at the BU detection and treatment center (CDTUB) of Allada (Department of the Atlantique, Benin) during the period from January 1st, 2006, to June 30th, 2008, with three matched controls (persons who had no signs or symptoms of active or inactive BU) for age, gender and village of residence per case. Contact with natural water sources, BU history in the family and the practice of consanguineous marriages. A total of 416 participants were included in this study, including 104 cases and 312 controls. BU history in the family (p<0.001), adjusted by daily contact with a natural water source (p = 0.007), was significantly associated with higher odds of having BU (OR; 95% CI = 5.5; 3.0-10.0). The practice of consanguineous marriage was not associated with the occurrence of BU (p = 0.40). Mendelian disorders could explain this finding, which may influence individual susceptibility by impairing immunity. This study suggests that a combination of genetic factors and behavioral risk factors may increase the susceptibility for developing BU.

Consanguineous Marriage as a Risk Factor for Developing Keratoconus

PubMed Central

JAMALI, Hossein; BEIGI, Vahid; SADEGHI-SARVESTANI, Ali

2018-01-01

Heredity plays an important role in keratoconus (KC). Consanguineous marriage (CM) can affect the transmission of recessively inherited conditions. We aimed to investigate the role of consanguineous marriage in the development of KC. This study included two groups: the first group comprised 415 patients who underwent surgery for KC for the first time at Khalili University Hospital (Shiraz, Iran), between 2010 and 2014; the second group comprised 415 healthy individuals who served as age- and sex-matched controls for the patient group. All study subjects were from the Fars province in Iran. CM type was evaluated by a standard checklist in both groups. The mean inbreeding coefficient (α) was evaluated and compared between the two groups. The percentage of parental first-cousin marriages was 35.4% in the patient group and 18.3% in the control group. The mean inbreeding coefficient (α) was 0.0291 in the patient group and 0.0135 in the control group. Patients with KC had a significantly higher mean inbreeding coefficient (α) than controls (T = 8, df = 828, P < 0.001). Our study suggests that CM can play a role in the pathogenesis of KC. As this disease is among the most frequent ocular disorders in our country, CM should be considered by health care systems within their screening programs. PMID:29644240

48XXYY Syndrome in an Adult with Type 2 Diabetes Mellitus, Unilateral Renal Aplasia, and Pigmentary Retinitis.

PubMed

Zantour, Baha; Sfar, Mohamed Habib; Younes, Samia; Alaya, Wafa; Kamoun, Mahdi; Mkaouar, Emna; Jerbi, Saida

2010-01-01

A 45-year-old male was referred for diabetes mellitus. Clinical examination found a family history of multiple precocious deaths, strong consanguinity, personal history of seizures during childhood, small testicles, small penis, sparse body hair, long arms and legs, dysmorphic features, mental retardation, dysarthria, tremor, and mild gait ataxia. Investigations found pigmentary retinitis, metabolic syndrome, unilateral renal aplasia, and hypergonadotropic hypogonadism, and ruled out mitochondrial cytopathy and leucodystrophy. Karyotype study showed a 48XXYY chromosomal type. Renal aplasia and pigmentary retinitis have not been described in 48XXYY patients. They may be related to the chromosomal sex aneuploidy, or caused by other genetic aberrations in light of the high consanguinity rate in the patient's family.

48XXYY Syndrome in an Adult with Type 2 Diabetes Mellitus, Unilateral Renal Aplasia, and Pigmentary Retinitis

PubMed Central

Zantour, Baha; Sfar, Mohamed Habib; Younes, Samia; Alaya, Wafa; Kamoun, Mahdi; Mkaouar, Emna; Jerbi, Saida

2010-01-01

A 45-year-old male was referred for diabetes mellitus. Clinical examination found a family history of multiple precocious deaths, strong consanguinity, personal history of seizures during childhood, small testicles, small penis, sparse body hair, long arms and legs, dysmorphic features, mental retardation, dysarthria, tremor, and mild gait ataxia. Investigations found pigmentary retinitis, metabolic syndrome, unilateral renal aplasia, and hypergonadotropic hypogonadism, and ruled out mitochondrial cytopathy and leucodystrophy. Karyotype study showed a 48XXYY chromosomal type. Renal aplasia and pigmentary retinitis have not been described in 48XXYY patients. They may be related to the chromosomal sex aneuploidy, or caused by other genetic aberrations in light of the high consanguinity rate in the patient's family. PMID:20827436

Dental findings and treatment in consanguinity associated congenital chronic familial neutropenia.

PubMed

Buduneli, Nurcan; Cogulu, Dilsah; Kardesler, Levent; Kütükçüler, Necil

2006-01-01

The purpose of this report is to describe dental findings and treatment of an 11-year old male patient and a 5-year old female patient, children of first cousins, suffering from severe benign congenital chronic familial neutropenia. This case report emphazises the importance of differential diagnosis of immunodeficiencies including congenital chronic familial neutropenia in the background of severe periodontal diseases and/or diffuse carious lesions in children.

Spondylo-meta-epiphyseal dysplasia (SMED), short limb-hand type: a congenital familial skeletal dysplasia with distinctive features and histopathology.

PubMed

Borochowitz, Z; Langer, L O; Gruber, H E; Lachman, R; Katznelson, M B; Rimoin, D L

1993-02-01

We report on a "new" severe short-limb bone dysplasia which can be labeled descriptively a spondylo-meta-epiphyseal dysplasia. The 3 patients were born to 2 unrelated Sepharadic Jewish families and a Puerto Rican family. Clinical abnormalities include small stature with short limbs including short hands, a short nose with wide nasal bridge and wide nostrils, a long philtrum, ocular hypertelorism, retro/micrognathia, and a narrow chest. Radiological abnormalities include platyspondyly, short tubular bones with very abnormal metaphyses and epiphyses beyond early infancy, short ribs, and a typical evolution of bony changes over time. Chondroosseous morphology and ultrastructure document sparse matrix and degenerating chondrocytes surrounded by dense amorphous material in the 1 patient studied. Consanguinity is present in 1 family. In addition to the described patient, 2 other short-limb sibs, who did not survive infancy, were born into this family. Even in the absence of any photographic or radiologic documentation of these other 2 infants, autosomal recessive mode of inheritance seems probable.

The Effect of Consanguineous Marriage on Reading Disability in the Arab Community

ERIC Educational Resources Information Center

Abu-Rabia, Salim; Maroun, Lateefeh

2005-01-01

The present study examined the effect of consanguineous marriage in the Arab community on reading disabilities of offspring. It examined whether the rate of reading disabilities was higher among offspring of first-cousin parents than offspring of unrelated parents; and whether reading-disabled children of first-cousin parents were more disabled in…

Identification and in silico characterization of p.G380R substitution in FGFR3, associated with achondroplasia in a non-consanguineous Pakistani family.

PubMed

Ajmal, Muhammad; Mir, Asif; Shoaib, Muhammad; Malik, Salman Akbar; Nasir, Muhammad

2017-07-05

The dimerization efficiency of FGFR3 transmembrane domain plays a critical role in the formation of a normal skeleton through the negative regulation of bone development. Recently, gain-of-function mutations in the transmembrane domain of FGFR3 has been described associated with an aberrant negative regulation, leading to the development of achondroplasia-group disorders, including achondroplasia (ACH), hypochondroplasia (HCH) and thanatophoric dysplasia (TD). Here, we describe a non-consanguineous Pakistani family with achondroplasia to explain hereditary basis of the disease. PCR-based linkage analysis using microsatellite markers was employed to localize the disease gene. Gene specific intronic primers were used to amplify the genomic DNA from all affected as well as phenotypically healthy individuals. Amplified PCR products were then subjected to Sanger sequencing and RFLP analysis to identify a potentially pathogenic mutation. The impact of identified mutation on FGFR3 protein's structure and stability was highlighted through different bioinformatics tools. Genetic screening of the family revealed a previously reported heterozygous c.1138 G > A (p.G380R) mutation in the coding exon 8 of FGFR3 gene. Identified genetic variation was confirmed in all affected individuals while healthy individuals and controls were found genotypically normal. The results were further validated by RFLP analysis as c.1138 G > A substitution generates a unique recognition site for SfcI endonuclease. Following SfcI digestion, the electrophoretic pattern of three bands/DNA fragments for each patient is indicative of heterozygous status of the disease allele. In silico studies of the mutant FGFR3 protein predicted to adversely affect the stability of FGFR3 protein. Mutation in the transmembrane domain may adversely affect the dimerization efficiency and overall stability of the FGFR3, leading to a constitutively active protein. As a result, an uncontrolled intracellular signaling

Human knockouts and phenotypic analysis in a cohort with a high rate of consanguinity

PubMed Central

Saleheen, Danish; Natarajan, Pradeep; Armean, Irina M.; Zhao, Wei; Rasheed, Asif; Khetarpal, Sumeet; Won, Hong-Hee; Karczewski, Konrad J.; O’Donnell-Luria, Anne H.; Samocha, Kaitlin E.; Weisburd, Benjamin; Gupta, Namrata; Zaidi, Mozzam; Samuel, Maria; Imran, Atif; Abbas, Shahid; Majeed, Faisal; Ishaq, Madiha; Akhtar, Saba; Trindade, Kevin; Mucksavage, Megan; Qamar, Nadeem; Zaman, Khan Shah; Yaqoob, Zia; Saghir, Tahir; Rizvi, Syed Nadeem Hasan; Memon, Anis; Mallick, Nadeem Hayyat; Ishaq, Mohammad; Rasheed, Syed Zahed; Memon, Fazal-ur-Rehman; Mahmood, Khalid; Ahmed, Naveeduddin; Do, Ron; Krauss, Ronald M.; MacArthur, Daniel G.; Gabriel, Stacey; Lander, Eric S.; Daly, Mark J.; Frossard, Philippe; Danesh, John; Rader, Daniel J.; Kathiresan, Sekar

2017-01-01

A major goal of biomedicine is to understand the function of every gene in the human genome.1 Loss-of-function (LoF) mutations can disrupt both copies of a given gene in humans and phenotypic analysis of such ‘human knockouts’ can provide insight into gene function. Consanguineous unions are more likely to result in offspring who carry LoF mutations in a homozygous state. In Pakistan, consanguinity rates are notably high.2 Here, we sequenced the protein-coding regions of 10,503 adult participants in the Pakistan Risk of Myocardial Infarction Study (PROMIS) designed to understand the determinants of cardiometabolic diseases in South Asians.3 We identified individuals carrying predicted LoF (pLoF) mutations in the homozygous state, and performed phenotypic analysis involving >200 biochemical and disease traits. We enumerated 49,138 rare (<1 % minor allele frequency) pLoF mutations. These pLoF mutations are predicted to knock out 1,317 genes in at least one participant. Homozygosity for pLoF mutations at PLAG27 was associated with absent enzymatic activity of soluble lipoprotein-associated phospholipase A2; at CYP2F1, with higher plasma interleukin-8 concentrations; at TREH, with lower concentrations of apoB-containing lipoprotein subfractions; at either A3GALT2 or NRG4, with markedly reduced plasma insulin C-peptide concentrations; and at SLC9A3R1, with mediators of calcium and phosphate signaling. Finally, APOC3 is a gene which retards clearance of plasma triglyceride-rich lipoproteins and where heterozygous deficiency confers protection against coronary heart disease.4,5 In Pakistan, we now observe APOC3 homozygous pLoF carriers; we recalled these knockout humans and challenged with an oral fat load. Compared with wild-type family members, APOC3 knockouts displayed marked blunting of the usual post-prandial rise in plasma triglycerides. Overall, these observations provide a roadmap for a ‘human knockout project’, a systematic effort to understand the

Human knockouts and phenotypic analysis in a cohort with a high rate of consanguinity.

PubMed

Saleheen, Danish; Natarajan, Pradeep; Armean, Irina M; Zhao, Wei; Rasheed, Asif; Khetarpal, Sumeet A; Won, Hong-Hee; Karczewski, Konrad J; O'Donnell-Luria, Anne H; Samocha, Kaitlin E; Weisburd, Benjamin; Gupta, Namrata; Zaidi, Mozzam; Samuel, Maria; Imran, Atif; Abbas, Shahid; Majeed, Faisal; Ishaq, Madiha; Akhtar, Saba; Trindade, Kevin; Mucksavage, Megan; Qamar, Nadeem; Zaman, Khan Shah; Yaqoob, Zia; Saghir, Tahir; Rizvi, Syed Nadeem Hasan; Memon, Anis; Hayyat Mallick, Nadeem; Ishaq, Mohammad; Rasheed, Syed Zahed; Memon, Fazal-Ur-Rehman; Mahmood, Khalid; Ahmed, Naveeduddin; Do, Ron; Krauss, Ronald M; MacArthur, Daniel G; Gabriel, Stacey; Lander, Eric S; Daly, Mark J; Frossard, Philippe; Danesh, John; Rader, Daniel J; Kathiresan, Sekar

2017-04-12

A major goal of biomedicine is to understand the function of every gene in the human genome. Loss-of-function mutations can disrupt both copies of a given gene in humans and phenotypic analysis of such 'human knockouts' can provide insight into gene function. Consanguineous unions are more likely to result in offspring carrying homozygous loss-of-function mutations. In Pakistan, consanguinity rates are notably high. Here we sequence the protein-coding regions of 10,503 adult participants in the Pakistan Risk of Myocardial Infarction Study (PROMIS), designed to understand the determinants of cardiometabolic diseases in individuals from South Asia. We identified individuals carrying homozygous predicted loss-of-function (pLoF) mutations, and performed phenotypic analysis involving more than 200 biochemical and disease traits. We enumerated 49,138 rare (<1% minor allele frequency) pLoF mutations. These pLoF mutations are estimated to knock out 1,317 genes, each in at least one participant. Homozygosity for pLoF mutations at PLA2G7 was associated with absent enzymatic activity of soluble lipoprotein-associated phospholipase A2; at CYP2F1, with higher plasma interleukin-8 concentrations; at TREH, with lower concentrations of apoB-containing lipoprotein subfractions; at either A3GALT2 or NRG4, with markedly reduced plasma insulin C-peptide concentrations; and at SLC9A3R1, with mediators of calcium and phosphate signalling. Heterozygous deficiency of APOC3 has been shown to protect against coronary heart disease; we identified APOC3 homozygous pLoF carriers in our cohort. We recruited these human knockouts and challenged them with an oral fat load. Compared with family members lacking the mutation, individuals with APOC3 knocked out displayed marked blunting of the usual post-prandial rise in plasma triglycerides. Overall, these observations provide a roadmap for a 'human knockout project', a systematic effort to understand the phenotypic consequences of complete

Efficiency of allogeneic hematopoietic SCT from HLA fully-matched non-sibling relatives: a new prospect of exploiting extended family search.

PubMed

Hamidieh, A A; Dehaghi, M Ostadali; Paragomi, P; Navaei, S; Jalali, A; Eslami, G Ghazizadeh; Behfar, M; Ghavamzadeh, A

2015-04-01

The best donors for hematopoietic SCT (HSCT) are fully-matched siblings. In patients without fully-matched siblings, HLA registries or cord blood banks are alternative strategies with some restrictions. Owing to the high rate of consanguineous marriage in our country, between 2006 and 2013, extended family searches were undertaken in Hematology-Oncology Research Center and Stem Cell Transplantation (HORCSCT), Tehran, Iran, in 523 HSCT candidates with parental consanguinity and no available HLA identical sibling. Fully-matched other-relative donors were found for 109 cases. We retrospectively studied the HSCT outcome in these patients. Median time to neutrophil engraftment was 13 days (range: 9-31days). In 83 patients, full chimerism and in 17 patients, mixed chimerism was achieved. Acute GvHD (aGvHD) grade II-IV appeared in 36 patients (33%). The frequency of aGvHD development in various familial subgroups was NS. Five patients expired before day+100. In the surviving 104 cases, chronic GvHD developed in 20 patients (19.2%). The distantly related subgroup had significantly a higher rate of cGvHD (P=0.04). The 2-year OS and disease-free survival (DFS) were 76.7±4.5% and 71.7±4.7%, respectively. No significant difference in OS (P=0.30) and DFS (P=0.80) was unraveled between various familial relationships. Our considerable rate of fully-matched non-sibling family members and the favorable outcome support the rationale for extended family search in regions where consanguineous marriage is widely practiced.

Training and HRD Strategies in Family and Non-Family Owned Small Businesses: A Comparative Approach.

ERIC Educational Resources Information Center

Matlay, Harry

2002-01-01

A survey of 6,000 British small businesses, 600 interviews, and 120 case studies found that 70-80% were family owned; most favored informal management styles. In family-owned businesses, training of nonfamily employees was considered less crucial; investments in the latter were related to long-term business strategies and potential succession.…

Genomic Runs of Homozygosity Record Population History and Consanguinity

PubMed Central

Kirin, Mirna; McQuillan, Ruth; Franklin, Christopher S.; Campbell, Harry; McKeigue, Paul M.; Wilson, James F.

2010-01-01

The human genome is characterised by many runs of homozygous genotypes, where identical haplotypes were inherited from each parent. The length of each run is determined partly by the number of generations since the common ancestor: offspring of cousin marriages have long runs of homozygosity (ROH), while the numerous shorter tracts relate to shared ancestry tens and hundreds of generations ago. Human populations have experienced a wide range of demographic histories and hold diverse cultural attitudes to consanguinity. In a global population dataset, genome-wide analysis of long and shorter ROH allows categorisation of the mainly indigenous populations sampled here into four major groups in which the majority of the population are inferred to have: (a) recent parental relatedness (south and west Asians); (b) shared parental ancestry arising hundreds to thousands of years ago through long term isolation and restricted effective population size (Ne), but little recent inbreeding (Oceanians); (c) both ancient and recent parental relatedness (Native Americans); and (d) only the background level of shared ancestry relating to continental Ne (predominantly urban Europeans and East Asians; lowest of all in sub-Saharan African agriculturalists), and the occasional cryptically inbred individual. Moreover, individuals can be positioned along axes representing this demographic historic space. Long runs of homozygosity are therefore a globally widespread and under-appreciated characteristic of our genomes, which record past consanguinity and population isolation and provide a distinctive record of the demographic history of an individual's ancestors. Individual ROH measures will also allow quantification of the disease risk arising from polygenic recessive effects. PMID:21085596

Familial steroid-sensitive nephrotic syndrome in Southern Israel: clinical and genetic observations.

PubMed

Landau, Daniel; Oved, Tal; Geiger, Dan; Abizov, Luba; Shalev, Hanna; Parvari, Ruti

2007-05-01

Reports on genetically informative steroid-responsive (sensitive) idiopathic nephrotic syndrome (SSNS) families are lacking. We studied an extended SSNS Bedouin (B) family with a high rate of consanguinity. The clinical presentation and steroid response of its 11 affected individuals were similar to those of sporadic SSNS (spontaneous remission towards puberty and minimal change disease by kidney biopsy). Genome-wide linkage analysis, using a 382 microsatellite-markers mapping set and additional markers adjacent to 80 candidate genes of the index family, did not support linkage to any chromosomal locus. Retrospective analysis of all additional children with SSNS treated by our institution in the past 20 years (n=96, 50% of them of Jewish origin) revealed another five non-related B families with 2-3 first-degree cousins affected with SSNS in each. The overall familial SSNS rate among the B population (excluding the index family) was 28%, compared with 4% among Jews (Js) (OR 1.8-64, P<0.005). There were more Bs with simple SSNS than there were Js (71% and 40%, respectively; OR 3.58, 95% CI 1.41-9.23, P<0.01). In summary, SSNS in this index family was not linked to any of the presently known chromosomal loci nor predicted to be caused by mutation in any one of a list of genes associated with nephrotic syndrome (NS). The presence of other B families affected by SSNS supports the role for susceptibility genes enrichment, exposing highly consanguineous populations to an increased incidence of SSNS.

Analyses of MMP20 Missense Mutations in Two Families with Hypomaturation Amelogenesis Imperfecta.

PubMed

Kim, Youn Jung; Kang, Jenny; Seymen, Figen; Koruyucu, Mine; Gencay, Koray; Shin, Teo Jeon; Hyun, Hong-Keun; Lee, Zang Hee; Hu, Jan C-C; Simmer, James P; Kim, Jung-Wook

2017-01-01

Amelogenesis imperfecta is a group of rare inherited disorders that affect tooth enamel formation, quantitatively and/or qualitatively. The aim of this study was to identify the genetic etiologies of two families presenting with hypomaturation amelogenesis imperfecta. DNA was isolated from peripheral blood samples obtained from participating family members. Whole exome sequencing was performed using DNA samples from the two probands. Sequencing data was aligned to the NCBI human reference genome (NCBI build 37.2, hg19) and sequence variations were annotated with the dbSNP build 138. Mutations in MMP20 were identified in both probands. A homozygous missense mutation (c.678T>A; p.His226Gln) was identified in the consanguineous Family 1. Compound heterozygous MMP20 mutations (c.540T>A, p.Tyr180 * and c.389C>T, p.Thr130Ile) were identified in the non-consanguineous Family 2. Affected persons in Family 1 showed hypomaturation AI with dark brown discoloration, which is similar to the clinical phenotype in a previous report with the same mutation. However, the dentition of the Family 2 proband exhibited slight yellowish discoloration with reduced transparency. Functional analysis showed that the p.Thr130Ile mutant protein had reduced activity of MMP20, while there was no functional MMP20 in the Family 1 proband. These results expand the mutational spectrum of the MMP20 and broaden our understanding of genotype-phenotype correlations in amelogenesis imperfecta.

Pitfalls of mapping a large Turkish consanguineous family with vertical monilethrix inheritance.

PubMed

Celep, F; Uzumcu, A; Sonmez, F M; Uyguner, O; Balci, Y Isik; Bahadir, S; Karaguzel, A

2009-01-01

Monilethrix, a rare autosomal dominant disease characterized by hair fragility and follicular hyperkeratosis, is caused by mutations in three type II hair cortex keratins. The human keratin family comprises 54 members, 28 type I and 26 type II. The phenotype shows variable penetrance and results in hair fragility and patchy dystrophic alopecia. In our study, Monilethrix was diagnosed on the basis of clinical characteristics and microscopic examination in a family with 11 affected members. Haplotype analysis was performed by three Simple Tandem Repeat markers (STR) and KRT86 gene was sequenced for the identification of the disease causing mutation. In the results of this, autosomal dominant mutation (E402K) in exon 7 of KRT86 gene was identified as a cause of Moniltherix in the large family from Turkey.

Severe congenital neutropenia in 2 siblings of consanguineous parents. The role of HAX1 deficiency.

PubMed

Mamishi, S; Esfahani, S A; Parvaneh, N; Diestelhorst, J; Rezaei, N

2009-01-01

Severe congenital neutropenia (SCN) is a rare primary immunodeficiency disease that is characterized by persistent severe neutropenia and severe early-onset bacterial infections. We report the case of 2 siblings with SCN who were the children of consanguineous parents. The HAX1 mutation was identified in both siblings. Both patients suffered from oral ulcers, candidiasis, respiratory tract infections, and diarrhea. A bone marrow biopsy, performed to determine the cause of their persistent severe neutropenia, revealed myeloid maturation arrest; thus confirming the diagnosis of SCN. Granulocyte colony-stimulating factor and prophylactic antibiotics were started. A molecular study revealed a homozygous W44X mutation of the HAX1 gene in both cases. HAX1 deficiency should be considered in any child with severe infections and neutropenia, especially in children of consanguineous parents. Early diagnosis and appropriate treatment could prevent complications in this group of patients.

Familial chondrocalcinosis in the Chiloe Islands, Chile.

PubMed Central

Reginato, A J; Hollander, J L; Martinez, V; Valenzuela, F; Schiapachasse, V; Covarrubias, E; Jacobelli, S; Arinoviche, R; Silcox, D; Ruiz, F

1975-01-01

Studies about chondrocalcinosis in the Chiloe Islands (Chile) showed the high frequency of the disease there and how most of it is aggregated in a few highly involved families. Pedigrees and the high degree of consanguinity among parents of index cases pointed to a recessive inheritance. The presence of common Caucasian anthropological features of genetic value in the patients and the lack of Indian mixture in three of the involved families, documented back to 1600, suggest a Caucasian origin of the mutation. Biochemical studies of the patients' synovial fluid showed a significant rise in pyrophosphate concentration. Calcium, phosphorus, and alkaline phosphatase concentrations were not different from a control group. PMID:168817

Discovery of four recessive developmental disorders using probabilistic genotype and phenotype matching among 4,125 families

PubMed Central

Ansari, Morad; Balasubramanian, Meena; Blyth, Moira; Brady, Angela F.; Clayton, Stephen; Cole, Trevor; Deshpande, Charu; Fitzgerald, Tomas W.; Foulds, Nicola; Francis, Richard; Gabriel, George; Gerety, Sebastian S.; Goodship, Judith; Hobson, Emma; Jones, Wendy D.; Joss, Shelagh; King, Daniel; Klena, Nikolai; Kumar, Ajith; Lees, Melissa; Lelliott, Chris; Lord, Jenny; McMullan, Dominic; O'Regan, Mary; Osio, Deborah; Piombo, Virginia; Prigmore, Elena; Rajan, Diana; Rosser, Elisabeth; Sifrim, Alejandro; Smith, Audrey; Swaminathan, Ganesh J.; Turnpenny, Peter; Whitworth, James; Wright, Caroline F.; Firth, Helen V.; Barrett, Jeffrey C.; Lo, Cecilia W.; FitzPatrick, David R.; Hurles, Matthew E.

2018-01-01

Discovery of most autosomal recessive disease genes has involved analysis of large, often consanguineous, multiplex families or small cohorts of unrelated individuals with a well-defined clinical condition. Discovery of novel dominant causes of rare, genetically heterogenous developmental disorders has been revolutionized by exome analysis of large cohorts of phenotypically diverse parent-offspring trios 1,2. Here we analysed 4,125 families with diverse, rare, genetically heterogeneous developmental disorders and identified four novel autosomal recessive disorders. These four disorders were identified by integrating Mendelian filtering (identifying probands with rare biallelic putatively damaging variants in the same gene) with statistical assessments of (i) the likelihood of sampling the observed genotypes from the general population, and (ii) the phenotypic similarity of patients with the same recessive candidate gene. This new paradigm promises to catalyse discovery of novel recessive disorders, especially those with less consistent or nonspecific clinical presentations, and those caused predominantly by compound heterozygous genotypes. PMID:26437029

Discovery of four recessive developmental disorders using probabilistic genotype and phenotype matching among 4,125 families.

PubMed

Akawi, Nadia; McRae, Jeremy; Ansari, Morad; Balasubramanian, Meena; Blyth, Moira; Brady, Angela F; Clayton, Stephen; Cole, Trevor; Deshpande, Charu; Fitzgerald, Tomas W; Foulds, Nicola; Francis, Richard; Gabriel, George; Gerety, Sebastian S; Goodship, Judith; Hobson, Emma; Jones, Wendy D; Joss, Shelagh; King, Daniel; Klena, Nikolai; Kumar, Ajith; Lees, Melissa; Lelliott, Chris; Lord, Jenny; McMullan, Dominic; O'Regan, Mary; Osio, Deborah; Piombo, Virginia; Prigmore, Elena; Rajan, Diana; Rosser, Elisabeth; Sifrim, Alejandro; Smith, Audrey; Swaminathan, Ganesh J; Turnpenny, Peter; Whitworth, James; Wright, Caroline F; Firth, Helen V; Barrett, Jeffrey C; Lo, Cecilia W; FitzPatrick, David R; Hurles, Matthew E

2015-11-01

Discovery of most autosomal recessive disease-associated genes has involved analysis of large, often consanguineous multiplex families or small cohorts of unrelated individuals with a well-defined clinical condition. Discovery of new dominant causes of rare, genetically heterogeneous developmental disorders has been revolutionized by exome analysis of large cohorts of phenotypically diverse parent-offspring trios. Here we analyzed 4,125 families with diverse, rare and genetically heterogeneous developmental disorders and identified four new autosomal recessive disorders. These four disorders were identified by integrating Mendelian filtering (selecting probands with rare, biallelic and putatively damaging variants in the same gene) with statistical assessments of (i) the likelihood of sampling the observed genotypes from the general population and (ii) the phenotypic similarity of patients with recessive variants in the same candidate gene. This new paradigm promises to catalyze the discovery of novel recessive disorders, especially those with less consistent or nonspecific clinical presentations and those caused predominantly by compound heterozygous genotypes.

Socio-demographic and consanguinity risk factors associated with low birthweight.

PubMed

Bener, Abdulbari; Saleh, Najah Mohammed; Salameh, Khalil Mohd Khalil; Basha, Basma; Joseph, Sharen; Al Buz, Rama

2013-05-01

To examine socio-demographic and biological risk factors associated with mothers giving birth to a low birthweight newborn among Arab women in Qatar. The case-control study was conducted at two main tertiary hospitals in Qatar in which participants were prospectively identified from January 2010 to April 2011. Data were collected by survey on maternal ethnicity, age, education, socioeconomic status, body mass index, consanguinity and gestational age. A total of 16,500 newborns were screened for low birthweight. A total of 863 mothers of low birthweight cases and an equal number of mothers of normal-weight babies were studied. Qatari mothers were found to be 1.2 times as likely to have a low birthweight (< 2500g) newborn compared to other Arab women (p < 0.057). Mothers with a primary school education were 1.6 times as likely as university educated mothers to have a low birthweight newborn (p < 0.006). Likewise, obese mothers were 1.5 times as likely as their normal-weight counterparts (p < 0.009). Consanguineous couples who were first-degree cousins were 1.9 times as likely as non-related couples to have a low birthweight newborn (p < 0.001). Newborns with a gestational age of < 37 weeks were 19.6 times as likely as those > or = 37 weeks to have a low birthweight (p < 0.001). The majority of the risk factors associated with low birthweight were modifiable. Health education campaigns need to target the most vulnerable groups to reduce the rates of low birthweight among Arabs in Qatar.

Collection of family health history for assessment of chronic disease risk in primary care.

PubMed

Powell, Karen P; Christianson, Carol A; Hahn, Susan E; Dave, Gaurav; Evans, Leslie R; Blanton, Susan H; Hauser, Elizabeth; Agbaje, Astrid; Orlando, Lori A; Ginsburg, Geoffrey S; Henrich, Vincent C

2013-01-01

Family health history can predict a patient's risk for common complex diseases. This project assessed the completeness of family health history data in medical charts and evaluated the utility of these data for performing risk assessments in primary care. Family health history data were collected and analyzed to determine the presence of quality indicators that are necessary for effective and accurate assessment of disease risk. More than 99% of the 390 paper charts analyzed contained information about family health history, which was usually scattered throughout the chart. Information on the health of the patient's parents was collected more often than information on the health of other relatives. Key information that was often not collected included age of disease onset, affected side of the family, and second-degree relatives affected. Less than 4% of patient charts included family health histories that were informative enough to accurately assess risk for common complex diseases. Limitations of this study include the small number of charts reviewed per provider, the fact that the sample consisted of primary care providers in a single geographic location, and the inability to assess ethnicity, consanguinity, and other indicators of the informativeness of family health history. The family health histories collected in primary care are usually not complete enough to assess the patient's risk for common complex diseases. This situation could be improved with use of tools that analyze the family health history information collected and provide risk-stratified decision support recommendations for primary care.

Genetic heterogeneity and consanguinity lead to a "double hit": homozygous mutations of MYO7A and PDE6B in a patient with retinitis pigmentosa.

PubMed

Goldenberg-Cohen, Nitza; Banin, Eyal; Zalzstein, Yael; Cohen, Ben; Rotenstreich, Ygal; Rizel, Leah; Basel-Vanagaite, Lina; Ben-Yosef, Tamar

2013-01-01

Retinitis pigmentosa (RP), the most genetically heterogeneous disorder in humans, actually represents a group of pigmentary retinopathies characterized by night blindness followed by visual-field loss. RP can appear as either syndromic or nonsyndromic. One of the most common forms of syndromic RP is Usher syndrome, characterized by the combination of RP, hearing loss, and vestibular dysfunction. The underlying cause of the appearance of syndromic and nonsyndromic RP in three siblings from a consanguineous Israeli Muslim Arab family was studied with whole-genome homozygosity mapping followed by whole exome sequencing. THE FAMILY WAS FOUND TO SEGREGATE NOVEL MUTATIONS OF TWO DIFFERENT GENES: myosin VIIA (MYO7A), which causes type 1 Usher syndrome, and phosphodiesterase 6B, cyclic guanosine monophosphate-specific, rod, beta (PDE6B), which causes nonsyndromic RP. One affected child was homozygous for both mutations. Since the retinal phenotype seen in this patient results from overlapping pathologies, one might expect to find severe retinal degeneration. Indeed, he was diagnosed with RP based on an abnormal electroretinogram (ERG) at a young age (9 months). However, this early diagnosis may be biased, as two of his older siblings had already been diagnosed, leading to increased awareness. At the age of 32 months, he had relatively good vision with normal visual fields. Further testing of visual function and structure at different ages in the three siblings is needed to determine whether the two RP-causing genes mutated in this youngest sibling confer increased disease severity. This report further supports the genetic heterogeneity of RP, and demonstrates how consanguinity could increase intrafamilial clustering of multiple hereditary diseases. Moreover, this report provides a unique opportunity to study the clinical implications of the coexistence of pathogenic mutations in two RP-causative genes in a human patient.

Obesity susceptibility loci in Qataris, a highly consanguineous Arabian population.

PubMed

Tomei, Sara; Mamtani, Ravinder; Al Ali, Rashid; Elkum, Naser; Abdulmalik, Maryam; Ismail, Awatef; Cheema, Sohaila; Rouh, Hekmat A; Aigha, Idil I; Hani, Fatima; Al-Samraye, Sura; Taher Aseel, Mona; El Emadi, Nada; Al Mujalli, Azza; Abdelkerim, Ahmed; Youssif, Siddik; Worschech, Andrea; El Sebakhy, Emad; Temanni, Ramzi; Khanna, Vineesh; Wang, Ena; Kizhakayil, Dhanya; Al-Thani, Al-Anood; Al-Thani, Mohammed; Lowenfels, Albert; Marincola, Francesco M; Sheikh, Javaid; Chouchane, Lotfi

2015-04-13

In Qataris, a population characterized by a small size and a high rate of consanguinity, between two-thirds to three-quarters of adults are overweight or obese. We investigated the relevance of 23 obesity-related loci in the Qatari population. Eight-hundred-four individuals assessed to be third generation Qataris were included in the study and assigned to 3 groups according to their body mass index (BMI): 190 lean (BMI < 25 kg/m(2)); 131 overweight (25 kg/m(2) ≤ BMI < 30 kg/m(2)) and 483 obese (BMI ≥ 30 kg/m(2)). Genomic DNA was isolated from peripheral blood and genotyped by TaqMan. Two loci significantly associated with obesity in Qataris: the TFAP2B variation (rs987237) (A allele versus G allele: chi-square = 10.3; P = 0.0013) and GNPDA2 variation (rs10938397) (A allele versus G allele: chi-square = 6.15; P = 0.013). The TFAP2B GG genotype negatively associated with obesity (OR = 0.21; P = 0.0031). Conversely, the GNDPA2 GG homozygous genotype associated with higher risk of obesity in subjects of age < 32 years (P = 0.0358). We showed a different genetic profile associated with obesity in the Qatari population compared to Western populations. Studying the genetic background of Qataris is of primary importance as the etiology of a given disease might be population-specific.

Loss-of-function mutations in the thyrotropin receptor gene as a major determinant of hyperthyrotropinemia in a consanguineous community.

PubMed

Tenenbaum-Rakover, Yardena; Grasberger, Helmut; Mamanasiri, Sunee; Ringkananont, Usanee; Montanelli, Lucia; Barkoff, Marla S; Dahood, Ahmad Mahameed-Hag; Refetoff, Samuel

2009-05-01

Resistance to TSH (RTSH) is a condition of impaired responsiveness of the thyroid gland to TSH, characterized by elevated serum TSH, low or normal thyroid hormone levels, and hypoplastic or normal-sized thyroid gland. The aim of the study was to evaluate the clinical course and the genotype-phenotype relationship of RTSH caused by two different TSH receptor (TSHR) gene mutations in a consanguineous population. We conducted a clinical and genetic investigation of 46 members of an extended family and 163 individuals living in the same town. In vitro functional studies of the mutant TSHRs were also performed. Two TSHR gene mutations (P68S and L653V) were identified in 33 subjects occurring as homozygous L653V (five subjects), heterozygous L653V (20 subjects), heterozygous P68S (four subjects), and compound heterozygous L653V/P68S (four subjects). With the exception of one individual with concomitant autoimmune thyroid disease, all homozygotes and compound heterozygotes presented with compensated RTSH (high TSH with free T(4) and T(3) in the normal range). Only nine of 24 heterozygotes had mild hyperthyrotropinemia. The L653V mutation resulted in a higher serum TSH concentration and showed a more severe in vitro abnormality than P68S. Haplotype analysis predicted a founder of the L653V six to seven generations earlier, whereas the P68S is older. Cross-sectional and prospective longitudinal studies indicate that TSH and T(4) concentrations remain stable over time. High frequency hyperthyrotropinemia in an Israeli Arab-Muslim consanguineous community is attributed to two inactivating TSHR gene mutations. Concordant genotype-phenotype was demonstrated clinically and by in vitro functional analysis. Retrospective and prospective studies indicate that in the absence of concomitant autoimmune thyroid disease, elevated TSH levels reflect stable compensated RTSH.

Genetic heterogeneity and consanguinity lead to a “double hit”: Homozygous mutations of MYO7A and PDE6B in a patient with retinitis pigmentosa

PubMed Central

Goldenberg-Cohen, Nitza; Banin, Eyal; Zalzstein, Yael; Cohen, Ben; Rotenstreich, Ygal; Rizel, Leah; Basel-Vanagaite, Lina

2013-01-01

Purpose Retinitis pigmentosa (RP), the most genetically heterogeneous disorder in humans, actually represents a group of pigmentary retinopathies characterized by night blindness followed by visual-field loss. RP can appear as either syndromic or nonsyndromic. One of the most common forms of syndromic RP is Usher syndrome, characterized by the combination of RP, hearing loss, and vestibular dysfunction. Methods The underlying cause of the appearance of syndromic and nonsyndromic RP in three siblings from a consanguineous Israeli Muslim Arab family was studied with whole-genome homozygosity mapping followed by whole exome sequencing. Results The family was found to segregate novel mutations of two different genes: myosin VIIA (MYO7A), which causes type 1 Usher syndrome, and phosphodiesterase 6B, cyclic guanosine monophosphate-specific, rod, beta (PDE6B), which causes nonsyndromic RP. One affected child was homozygous for both mutations. Since the retinal phenotype seen in this patient results from overlapping pathologies, one might expect to find severe retinal degeneration. Indeed, he was diagnosed with RP based on an abnormal electroretinogram (ERG) at a young age (9 months). However, this early diagnosis may be biased, as two of his older siblings had already been diagnosed, leading to increased awareness. At the age of 32 months, he had relatively good vision with normal visual fields. Further testing of visual function and structure at different ages in the three siblings is needed to determine whether the two RP-causing genes mutated in this youngest sibling confer increased disease severity. Conclusions This report further supports the genetic heterogeneity of RP, and demonstrates how consanguinity could increase intrafamilial clustering of multiple hereditary diseases. Moreover, this report provides a unique opportunity to study the clinical implications of the coexistence of pathogenic mutations in two RP-causative genes in a human patient. PMID:23882135

[Consanguineous marriage and morbi-mortality, short literature review based on an exceptional association: Usher syndrome and Von Recklinghausen neurofibromatosis].

PubMed

Atipo-Tsiba, Pépin-Williams

2016-01-01

Usher syndrome is defined by the association of a progressive or non-progressive congenital sensorineural hearing loss with variable severity and a gradually blinding pigmentary retinopathy. Von Recklinghausen neurofibromatosis or Neurofibromatosis type 1 is the major clinically form of neurofibromatosis which occurs in approximately 90% of cases. Both types of disease are genetic in origin with very low prevalence. The probability of co-occurrence of these diseases in a single individual is exceptional. Inbreeding, as well as all genetic diseases, increases quite significantly the probability of their occurrence. Consanguineous marriages are still widespread in Maghreb and in some regions of the western African. This observation reports an exceptional case of this association in a 40-year-old man of Mauritanian origin born from a consanguineous union.

The prevalence of attention deficit hyperactivity symptoms in schoolchildren in a highly consanguineous community.

PubMed

Bener, Abdulbari; Al Qahtani, Razna; Teebi, Ahmad S; Bessisso, Mohammed

2008-01-01

The objective of the present study was to find the prevalence of attention deficit hyperactivity (ADH) symptoms in a sample of primary schoolchildren in Qatar and investigate the behaviour of the children with and without ADH symptoms in a highly consanguineous community. A total of 2,500 primary school students, aged 6-12 years, were randomly selected from the government primary schools, and 1,869 students (947 boys and 922 girls) gave consent to participate in this study. An Arabic questionnaire was used to collect the sociodemographic variables and a standardized Arabic version of the Conners' Teacher Rating Scale for ADH symptoms. Of the 947 boys, 158 (16.7%; 95% confidence interval, CI, 14.4-19.2) and of the 922 girls, 50 (5.4%; 95% CI 4.1-7.1) scored above the cut-off (>or=15) for ADH symptoms, thus giving an overall prevalence of 11.1% (95% CI 9.7-12.6). The children who had higher scores for ADH symptoms were in the age group of 6-9 years. Children who had higher scores for ADH symptoms had a poorer school performance than those with lower scores (p = 0.002). Two hundred (96.2%) children with ADH were disobedient, 126 (60.6%) noisy and hyperactive, 76 (36.5%) very cranky, 78 (37.5%) troublesome and 79 (37.9%) nervous. The logistic regression identified socio-economic condition, number of children, school performance and poor relationship between parents as the main contributors to ADH. Although the univariate analysis showed a significant relationship (p = 0.010) between ADH symptoms and consanguineous parents, logistic regression did not support this association (p = 0.075). This suggests that consanguinity has no impact on ADH children. The study revealed that ADH is a common problem among schoolchildren. The children with higher scores for ADH symptoms had a poorer school performance than those with lower scores. A significant difference exists between the behaviour of children with and without ADH. (c) 2008 S. Karger AG, Basel.

The Genetic Causes of Nonsyndromic Congenital Retinal Detachment: A Genetic and Phenotypic Study of Pakistani Families.

PubMed

Keser, Vafa; Khan, Ayesha; Siddiqui, Sorath; Lopez, Irma; Ren, Huanan; Qamar, Raheel; Nadaf, Javad; Majewski, Jacek; Chen, Rui; Koenekoop, Robert K

2017-02-01

To evaluate consanguineous pedigrees from Pakistan with a clinical diagnosis of nonsyndromic congenital retinal nonattachment (NCRNA) and identify genes responsible for the disease as currently only one NCRNA gene is known (atonal basic helix-loop-helix transcription factor 7: ATOH7). We implemented a three-step genotyping platform: single nucleotide polymorphism genotyping to identify loss of heterozygosity regions in patients, Retinal Information Network panel screening for mutations in currently known retinal genes. Negative patients were then subjected to whole exome sequencing. We evaluated 21 consanguineous NCRNA pedigrees and identified the causal mutations in known retinal genes in 13 out of our 21 families. We found mutations in ATOH7 in three families. Surprisingly, we then found mutations in familial exudative vitreoretinopathy (FEVR) genes; low-density lipoprotein receptor-related protein 5 mutations (six families), tetraspanin 12 mutations (two families), and NDP mutations (two families). Thus, 62% of the patients were successfully genotyped in our study with seven novel and six previously reported mutations in known retinal genes. Although the clinical diagnosis of all children was NCRNA with severe congenital fibrotic retinal detachments, the molecular diagnosis determined that the disease process was in fact a very severe form of FEVR in 10 families. Because severe congenital retinal detachment has not been previously associated with all the FEVR genes, we have thus expanded the phenotypic spectrum of FEVR, a highly variable retinal detachment phenotype that has clinical overlap with NCRNA. We identified seven novel mutations. We also established for the first time genetic overlap between the Iranian and Pakistani populations. We identified eight NCRNA families that do not harbor mutations in any known retinal genes, suggesting novel causal genes in these families.

Pentalogy of Cantrell: report of a case with consanguineous parents.

PubMed

Pachajoa, Harry; Barragán, Arelis; Potes, Angela; Torres, Javier; Isaza, Carolina

2010-01-01

Pentalogy of Cantrell is a syndrome evidencing five anomalies: a midline, upper abdominal wall abnormality; lower sternal defect; anterior diaphragmatic defect; diaphragmatic pericardial defect, and congenital abnormalities of the heart. Its prevalence is one in every 65,000 live births and a survival rate that is low if the fall the five defects are present or the gravity of the cardiac anomalies. It may be diagnosed during the first trimester obstetric ultrasound. For postnatal care, emission-computed tomography and magnetic resonance imaging is recommended for a clear definition of the extent of the defect and to design a course of corrective surgery. Herein, a case of pentology of Cantrell is reported for a child offspring of consanguineous parents.

From "New Genetics" to Everyday Knowledge: Ideas about How Genetic Diseases Are Transmitted in Two Large Brazilian Families

ERIC Educational Resources Information Center

Santos, Silvana; Bizzo, Nelio

2005-01-01

This study focuses on everyday or lay understandings of inheritance. In the northeastern Brazil, 100 individuals were interviewed in order to describe how they explain the origin of genetic disorders affecting their relatives for several generations. There were involved 60 individuals from a large consanguineous family with many members affected…

Development of a Family Resource Directory for Employees of a Small Business.

ERIC Educational Resources Information Center

Johnson, Wanda

Driven by a competitive environment with other employers to maintain a quality workforce, businesses are increasingly becoming aware of the necessity to assist employees with programs and services regarding family needs. Unfortunately, most small to medium size companies are either ignorant of the necessity for family friendly services or lack the…

Patterns of Relating Between Physicians and Medical Assistants in Small Family Medicine Offices

PubMed Central

Elder, Nancy C.; Jacobson, C. Jeffrey; Bolon, Shannon K.; Fixler, Joseph; Pallerla, Harini; Busick, Christina; Gerrety, Erica; Kinney, Dee; Regan, Saundra; Pugnale, Michael

2014-01-01

PURPOSE The clinician-colleague relationship is a cornerstone of relationship-centered care (RCC); in small family medicine offices, the clinician–medical assistant (MA) relationship is especially important. We sought to better understand the relationship between MA roles and the clinician-MA relationship within the RCC framework. METHODS We conducted an ethnographic study of 5 small family medicine offices (having <5 clinicians) in the Cincinnati Area Research and Improvement Group (CARInG) Network using interviews, surveys, and observations. We interviewed 19 MAs and supervisors and 11 clinicians (9 family physicians and 2 nurse practitioners) and observed 15 MAs in practice. Qualitative analysis used the editing style. RESULTS MAs’ roles in small family medicine offices were determined by MA career motivations and clinician-MA relationships. MA career motivations comprised interest in health care, easy training/workload, and customer service orientation. Clinician-MA relationships were influenced by how MAs and clinicians respond to their perceptions of MA clinical competence (illustrated predominantly by comparing MAs with nurses) and organizational structure. We propose a model, trust and verify, to describe the structure of the clinician-MA relationship. This model is informed by clinicians’ roles in hiring and managing MAs and the social familiarity of MAs and clinicians. Within the RCC framework, these findings can be seen as previously undefined constraints and freedoms in what is known as the Complex Responsive Process of Relating between clinicians and MAs. CONCLUSIONS Improved understanding of clinician-MA relationships will allow a better appreciation of how clinicians and MAs function in family medicine teams. Our findings may assist small offices undergoing practice transformation and guide future research to improve the education, training, and use of MAs in the family medicine setting. PMID:24615311

Retinal detachment and cataract, facial dysmorphism, generalized osteoporosis, immobile spine and platyspondyly in a consanguinous kindred--a possible new syndrome.

PubMed

Schmidt, H; Rudolph, G; Hergersberg, M; Schneider, K; Moradi, S; Meitinger, T

2001-02-01

We report on a consanguineous family with 6 children (out of 7) affected by a spondylo-ocular syndrome. Clinical features include cataract, loss of vision due to retinal detachment, facial dysmorphism, facial hypotonia, normal height with disproportional short trunk, immobile spine with thorakal kyphosis and reduced lumbal lordosis. On ophthalmological examination of the index patient, a dense cataract and complete retinal detachment could be detected on the right eye. On the left eye, an absent lens nucleus was found, but no retinal detachment. On radiological examination, there was generalized moderate osteoporosis; the spine showed marked platyspondyly and the bone age was advanced. On laboratory investigations, a normal excretion of amino acids, mucopolysaccharides and oligosaccharides could be found. The phenotypical spectrum observed in the 6 affected individuals was rather uniform. The karyotype was normal in all affected children. This hitherto undescribed combination of oculo-skeletal symptoms shows most resemblance with connective tissue disorders, suggesting a range of candidate genes for mutation analysis.

Novel mutations of MYO7A and USH1G in Israeli Arab families with Usher syndrome type 1.

PubMed

Rizel, Leah; Safieh, Christine; Shalev, Stavit A; Mezer, Eedy; Jabaly-Habib, Haneen; Ben-Neriah, Ziva; Chervinsky, Elena; Briscoe, Daniel; Ben-Yosef, Tamar

2011-01-01

This study investigated the genetic basis for Usher syndrome type 1 (USH1) in four consanguineous Israeli Arab families. Haplotype analysis for all known USH1 loci was performed in each family. In families for which haplotype analysis was inconclusive, we performed genome-wide homozygosity mapping using a single nucleotide polymorphism (SNP) array. For mutation analysis, specific primers were used to PCR amplify the coding exons of the MYO7A, USH1C, and USH1G genes including intron-exon boundaries. Mutation screening was performed with direct sequencing. A combination of haplotype analysis and genome-wide homozygosity mapping indicated linkage to the USH1B locus in two families, USH1C in one family and USH1G in another family. Sequence analysis of the relevant genes (MYO7A, USH1C, and USH1G) led to the identification of pathogenic mutations in all families. Two of the identified mutations are novel (c.1135-1147dup in MYO7A and c.206-207insC in USH1G). USH1 is a genetically heterogenous condition. Of the five USH1 genes identified to date, USH1C and USH1G are the rarest contributors to USH1 etiology worldwide. It is therefore interesting that two of the four Israeli Arab families reported here have mutations in these two genes. This finding further demonstrates the unique genetic structure of the Israeli population in general, and the Israeli Arab population in particular, which due to high rates of consanguinity segregates many rare autosomal recessive genetic conditions.

Localization of A Novel Autosomal Recessive Non-Syndromic Hearing Impairment Locus (DFNB38) to 6q26–q27 in a Consanguineous Kindred from Pakistan

PubMed Central

Ansar, Muhammad; Ramzan, Mohammad; Pham, Thanh L.; Yan, Kai; Jamal, Syed Muhammad; Haque, Sayedul; Ahmad, Wasim; Leal, Suzanne M.

2010-01-01

For autosomal recessive nonsyndromic hearing impairment over 30 loci have been mapped and 19 genes have been identified. DFNB38, a novel locus for autosomal recessive nonsyndromic hearing impairment, was localized in a consanguineous Pakistani kindred to 6q26–q27. The affected family members present with profound prelingual sensorineural hearing impairment and use sign language for communications. Linkage was established to microsatellite markers located on chromosome 6q26–q27 (Multipoint lod score 3.6). The genetic region for DFNB38 spans 10.1 cM according to the Marshfield genetic map and is bounded by markers D6S980 and D6S1719. This genetic region corresponds to 3.4 MB on the sequence-based physical map. PMID:12890929

Assessing the Local Need for Family and Child Care Services: A Small Area Utilization Analysis.

ERIC Educational Resources Information Center

Percy, Andrew; Carr-Hill, Roy; Dixon, Paul; Jamison, James Q.

2000-01-01

Describes study of administrative data from Northern Ireland on the costs of family and child care services, using small area utilization modeling, to derive a new set of needs indicators that could be used within the family and child care capitation funding formula. Argues that small area utilization modeling produces a fairer and more equitable…

The Genetic Causes of Nonsyndromic Congenital Retinal Detachment: A Genetic and Phenotypic Study of Pakistani Families

PubMed Central

Keser, Vafa; Khan, Ayesha; Siddiqui, Sorath; Lopez, Irma; Ren, Huanan; Qamar, Raheel; Nadaf, Javad; Majewski, Jacek; Chen, Rui; Koenekoop, Robert K.

2017-01-01

Purpose To evaluate consanguineous pedigrees from Pakistan with a clinical diagnosis of nonsyndromic congenital retinal nonattachment (NCRNA) and identify genes responsible for the disease as currently only one NCRNA gene is known (atonal basic helix-loop-helix transcription factor 7: ATOH7). Methods We implemented a three-step genotyping platform: single nucleotide polymorphism genotyping to identify loss of heterozygosity regions in patients, Retinal Information Network panel screening for mutations in currently known retinal genes. Negative patients were then subjected to whole exome sequencing. Results We evaluated 21 consanguineous NCRNA pedigrees and identified the causal mutations in known retinal genes in 13 out of our 21 families. We found mutations in ATOH7 in three families. Surprisingly, we then found mutations in familial exudative vitreoretinopathy (FEVR) genes; low-density lipoprotein receptor-related protein 5 mutations (six families), tetraspanin 12 mutations (two families), and NDP mutations (two families). Thus, 62% of the patients were successfully genotyped in our study with seven novel and six previously reported mutations in known retinal genes. Conclusions Although the clinical diagnosis of all children was NCRNA with severe congenital fibrotic retinal detachments, the molecular diagnosis determined that the disease process was in fact a very severe form of FEVR in 10 families. Because severe congenital retinal detachment has not been previously associated with all the FEVR genes, we have thus expanded the phenotypic spectrum of FEVR, a highly variable retinal detachment phenotype that has clinical overlap with NCRNA. We identified seven novel mutations. We also established for the first time genetic overlap between the Iranian and Pakistani populations. We identified eight NCRNA families that do not harbor mutations in any known retinal genes, suggesting novel causal genes in these families. PMID:28192794

Family health history reporting is sensitive to small changes in wording.

PubMed

Conway-Pearson, Liam S; Christensen, Kurt D; Savage, Sarah K; Huntington, Noelle L; Weitzman, Elissa R; Ziniel, Sonja I; Bacon, Phoebe; Cacioppo, Cara N; Green, Robert C; Holm, Ingrid A

2016-12-01

Family health history is often collected through single-item queries that ask patients whether their family members are affected by certain conditions. The specific wording of these queries may influence what individuals report. Parents of Boston Children's Hospital patients were invited to participate in a Web-based survey about the return of individual genomic research results regarding their children. Participants reported whether 11 types of medical conditions affected them or their family. Randomization determined whether participants were specifically instructed to consider their extended family. Family health history was reported by 2,901 participants. Those asked to consider their extended family were more likely to report a positive family history for 8 of 11 medical conditions. The largest differences were observed for cancer (65.1 vs. 45.7%; P < 0.001), cardiovascular conditions (72.5 vs. 56.0%; P < 0.001), and endocrine/hormonal conditions (50.9 vs. 36.7%; P < 0.001). Small alterations to the way family health history queries are worded can substantially change patient responses. Clinicians and researchers need to be sensitive about patients' tendencies to omit extended family from health history reporting unless specifically asked to consider them.Genet Med 18 12, 1308-1311.

A Novel Homozygous Mutation in SPTBN2 Leads to Spinocerebellar Ataxia in a Consanguineous Family: Report of a New Infantile-Onset Case and Brief Review of the Literature.

PubMed

Al-Muhaizea, Mohammad A; AlMutairi, Faten; Almass, Rawan; AlHarthi, Safinaz; Aldosary, Mazhor S; Alsagob, Maysoon; AlOdaib, Ali; Colak, Dilek; Kaya, Namik

2018-06-01

The objective of this study was the identification of likely genes and mutations associated with an autosomal recessive (AR) rare spinocerebellar ataxia (SCA) phenotype in two patients with infantile onset, from a consanguineous family. Using genome-wide SNP screening, autozygosity mapping, targeted Sanger sequencing and nextgen sequencing, family segregation analysis, and comprehensive neuropanel, we discovered a novel mutation in SPTBN2. Next, we utilized multiple sequence alignment of amino acids from various species as well as crystal structures provided by protein data bank (PDB# 1WYQ and 1WJM) to model the mutation site and its effect on β-III-spectrin. Finally, we used various bioinformatic classifiers to determine pathogenicity of the missense variant. A comprehensive clinical and diagnostic workup including radiological exams were performed on the patients as part of routine patient care. The homozygous missense variant (c.1572C>T; p.R414C) detected in exon 2 was fully segregated in the family and absent in a large ethnic cohort as well as publicly available data sets. Our comprehensive targeted sequencing approaches did not reveal any other likely candidate variants or mutations in both patients. The two male siblings presented with delayed motor milestones and cognitive and learning disability. Brain MRI revealed isolated cerebellar atrophy more marked in midline inferior vermis at ages of 3 and 6.5 years. Sequence alignments of the amino acids for β-III-spectrin indicated that the arginine at 414 is highly conserved among various species and located towards the end of first spectrin repeat domain. Inclusive bioinformatic analysis predicted that the variant is to be damaging and disease causing. In addition to the novel mutation, a brief literature review of the previously reported mutations as well as clinical comparison of the cases were also presented. Our study reviews the previously reported SPTBN2 mutations and cases. Moreover, the novel

A novel NDUFV1 gene mutation in complex I deficiency in consanguineous siblings with brainstem lesions and Leigh syndrome.

PubMed

Vilain, C; Rens, C; Aeby, A; Balériaux, D; Van Bogaert, P; Remiche, G; Smet, J; Van Coster, R; Abramowicz, M; Pirson, I

2012-09-01

Although deficiency of complex I of the mitochondrial respiratory chain is a frequent cause of encephalopathy in children, only a few mutations have been reported in each of its subunits. In the absence of families large enough for conclusive segregation analysis and of robust functional testing, it is difficult to unequivocally show the causality of the observed mutations and to delineate genotype-phenotype correlations, making additional observations necessary. We observed two consanguineous siblings with an early-onset encephalopathy, medulla, brainstem and mesencephalon lesions on brain magnetic resonance imaging and death before 8 months of age, caused by a complex I deficiency. We used a homozygosity mapping approach and identified a missense mutation in the NDUFV1 gene. The mutation, p.Arg386His, affects a highly conserved residue, contiguous to a cysteine residue known to coordinate an Fe ion. This observation adds to our understanding of complex I deficiency disease. It validates the important role of Arg386 and therefore supports the current molecular model of iron-sulfur clusters in NDUFV1. © 2011 John Wiley & Sons A/S.

Homozygosity mapping and targeted genomic sequencing reveal the gene responsible for cerebellar hypoplasia and quadrupedal locomotion in a consanguineous kindred

PubMed Central

Gulsuner, Suleyman; Tekinay, Ayse Begum; Doerschner, Katja; Boyaci, Huseyin; Bilguvar, Kaya; Unal, Hilal; Ors, Aslihan; Onat, O. Emre; Atalar, Ergin; Basak, A. Nazli; Topaloglu, Haluk; Kansu, Tulay; Tan, Meliha; Tan, Uner; Gunel, Murat; Ozcelik, Tayfun

2011-01-01

The biological basis for the development of the cerebro-cerebellar structures required for posture and gait in humans is poorly understood. We investigated a large consanguineous family from Turkey exhibiting an extremely rare phenotype associated with quadrupedal locomotion, mental retardation, and cerebro-cerebellar hypoplasia, linked to a 7.1-Mb region of homozygosity on chromosome 17p13.1–13.3. Diffusion weighted imaging and fiber tractography of the patients' brains revealed morphological abnormalities in the cerebellum and corpus callosum, in particular atrophy of superior, middle, and inferior peduncles of the cerebellum. Structural magnetic resonance imaging showed additional morphometric abnormalities in several cortical areas, including the corpus callosum, precentral gyrus, and Brodmann areas BA6, BA44, and BA45. Targeted sequencing of the entire homozygous region in three affected individuals and two obligate carriers uncovered a private missense mutation, WDR81 p.P856L, which cosegregated with the condition in the extended family. The mutation lies in a highly conserved region of WDR81, flanked by an N-terminal BEACH domain and C-terminal WD40 beta-propeller domains. WDR81 is predicted to be a transmembrane protein. It is highly expressed in the cerebellum and corpus callosum, in particular in the Purkinje cell layer of the cerebellum. WDR81 represents the third gene, after VLDLR and CA8, implicated in quadrupedal locomotion in humans. PMID:21885617

Sex linked versus autosomal inbreeding coefficient in close consanguineous marriages in the Basque country and Castile (Spain): genetic implications.

PubMed

Calderón, R; Morales, B; Peña, J A; Delgado, J

1995-10-01

Pedigree structures of 161 uncle/niece-aunt/nephew and 4420 first cousin consanguineous marriages registered during the 19th and 20th centuries in two large and very different Spanish regions have been analysed and their genetic consequences evaluated. The frequencies of the different pedigree subtypes within each degree of relationship were quite similar in both populations despite significant heterogeneity in inbreeding patterns. The mean X-linked inbreeding coefficient (Fx) for each type of cousin mating was calculated and compared to that expected for autosomal genes (F). The effect of genealogical structure on the Fx/F ratio was compared to different cultural populations worldwide. Preferentiality and avoidance of close consanguinity along with specific types of pedigrees are discussed on the basis of premarital migration and sociocultural rules still deeply rooted in certain human groups. By admitting that the observed Fx coefficient is usually higher than F in most human populations some remarks have been made in terms of population genetic risk.

Distinct mutations with different inheritance mode caused similar retinal dystrophies in one family: a demonstration of the importance of genetic annotations in complicated pedigrees.

PubMed

Chen, Xue; Sheng, Xunlun; Liu, Yani; Li, Zili; Sun, Xiantao; Jiang, Chao; Qi, Rui; Yuan, Shiqin; Wang, Xuhui; Zhou, Ge; Zhen, Yanyan; Xie, Ping; Liu, Qinghuai; Yan, Biao; Zhao, Chen

2018-05-29

Retinitis pigmentosa (RP) is the most common form of inherited retinal dystrophy presenting remarkable genetic heterogeneity. Genetic annotations would help with better clinical assessments and benefit gene therapy, and therefore should be recommended for RP patients. This report reveals the disease causing mutations in two RP pedigrees with confusing inheritance patterns using whole exome sequencing (WES). Twenty-five participants including eight patients from two families were recruited and received comprehensive ophthalmic evaluations. WES was applied for mutation identification. Bioinformatics annotations, intrafamilial co-segregation tests, and in silico analyses were subsequently conducted for mutation verification. All patients were clinically diagnosed with RP. The first family included two siblings born to parents with consanguineous marriage; however, no potential pathogenic variant was found shared by both patients. Further analysis revealed that the female patient carried a recurrent homozygous C8ORF37 p.W185*, while the male patient had hemizygous OFD1 p.T120A. The second family was found to segregate mutations in two genes, TULP1 and RP1. Two patients born to consanguineous marriage carried homozygous TULP1 p.R419W, while a recurrent heterozygous RP1 p.L762Yfs*17 was found in another four patients presenting an autosomal dominant inheritance pattern. Crystal structural analysis further indicated that the substitution from arginine to tryptophan at the highly conserved residue 419 of TULP1 could lead to the elimination of two hydrogen bonds between residue 419 and residues V488 and S534. All four genes, including C8ORF37, OFD1, TULP1 and RP1, have been previously implicated in RP etiology. Our study demonstrates the coexistence of diverse inheritance modes and mutations affecting distinct disease causing genes in two RP families with consanguineous marriage. Our data provide novel insights into assessments of complicated pedigrees, reinforce the

Domestic violence and consanguineous marriages - perspective from Rawalpindi, Pakistan.

PubMed

Shaikh, M Ali; Kayani, A; Shaikh, I Ali

2014-01-09

Domestic violence is globally endemic and adversely impacts the health and economic well-being of women and society. This study used the standardized and validated assessment instrument "Woman Abuse Screening Tool" to study the prevalence of various forms of domestic violence among married women. The relationship between domestic violence and consanguineous marriage was studied using the chi-squared test. Cumulatively, 1010 married women were interviewed. Emotional abuse was the most commonly reported abuse, reported by 721 (71.4%) women as either often or sometimes, followed by sexual abuse and physical abuse, reported by 527 (52.2%) and 511 (50.6%) respectively. Being married to one's cousin did not protect married women from being abused either emotionally or physically by their husbands; thsi was statistically significant. There is a need for better understanding of the magnitude and scale of domestic violence in Pakistan by using standardized assessment tools for meaningful comparisons across different parts of the country over time.

Homozygosity Mapping in Leber Congenital Amaurosis and Autosomal Recessive Retinitis Pigmentosa in South Indian Families

PubMed Central

Srilekha, Sundaramurthy; Arokiasamy, Tharigopala; Srikrupa, Natarajan N.; Umashankar, Vetrivel; Meenakshi, Swaminathan; Sen, Parveen; Kapur, Suman; Soumittra, Nagasamy

2015-01-01

Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP) are retinal degenerative diseases which cause severe retinal dystrophy affecting the photoreceptors. LCA is predominantly inherited as an autosomal recessive trait and contributes to 5% of all retinal dystrophies; whereas RP is inherited by all the Mendelian pattern of inheritance and both are leading causes of visual impairment in children and young adults. Homozygosity mapping is an efficient strategy for mapping both known and novel disease loci in recessive conditions, especially in a consanguineous mating, exploiting the fact that the regions adjacent to the disease locus will also be homozygous by descent in such inbred children. Here we have studied eleven consanguineous LCA and one autosomal recessive RP (arRP) south Indian families to know the prevalence of mutations in known genes and also to know the involvement of novel loci, if any. Complete ophthalmic examination was done for all the affected individuals including electroretinogram, fundus photograph, fundus autofluorescence, and optical coherence tomography. Homozygosity mapping using Affymetrix 250K HMA GeneChip on eleven LCA families followed by screening of candidate gene(s) in the homozygous block identified mutations in ten families; AIPL1 – 3 families, RPE65- 2 families, GUCY2D, CRB1, RDH12, IQCB1 and SPATA7 in one family each, respectively. Six of the ten (60%) mutations identified are novel. Homozygosity mapping using Affymetrix 10K HMA GeneChip on the arRP family identified a novel nonsense mutation in MERTK. The mutations segregated within the family and was absent in 200 control chromosomes screened. In one of the eleven LCA families, the causative gene/mutation was not identified but many homozygous blocks were noted indicating that a possible novel locus/gene might be involved. The genotype and phenotype features, especially the fundus changes for AIPL1, RPE65, CRB1, RDH12 genes were as reported earlier. PMID:26147992

Homozygosity Mapping in Leber Congenital Amaurosis and Autosomal Recessive Retinitis Pigmentosa in South Indian Families.

PubMed

Srilekha, Sundaramurthy; Arokiasamy, Tharigopala; Srikrupa, Natarajan N; Umashankar, Vetrivel; Meenakshi, Swaminathan; Sen, Parveen; Kapur, Suman; Soumittra, Nagasamy

2015-01-01

Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP) are retinal degenerative diseases which cause severe retinal dystrophy affecting the photoreceptors. LCA is predominantly inherited as an autosomal recessive trait and contributes to 5% of all retinal dystrophies; whereas RP is inherited by all the Mendelian pattern of inheritance and both are leading causes of visual impairment in children and young adults. Homozygosity mapping is an efficient strategy for mapping both known and novel disease loci in recessive conditions, especially in a consanguineous mating, exploiting the fact that the regions adjacent to the disease locus will also be homozygous by descent in such inbred children. Here we have studied eleven consanguineous LCA and one autosomal recessive RP (arRP) south Indian families to know the prevalence of mutations in known genes and also to know the involvement of novel loci, if any. Complete ophthalmic examination was done for all the affected individuals including electroretinogram, fundus photograph, fundus autofluorescence, and optical coherence tomography. Homozygosity mapping using Affymetrix 250K HMA GeneChip on eleven LCA families followed by screening of candidate gene(s) in the homozygous block identified mutations in ten families; AIPL1 - 3 families, RPE65- 2 families, GUCY2D, CRB1, RDH12, IQCB1 and SPATA7 in one family each, respectively. Six of the ten (60%) mutations identified are novel. Homozygosity mapping using Affymetrix 10K HMA GeneChip on the arRP family identified a novel nonsense mutation in MERTK. The mutations segregated within the family and was absent in 200 control chromosomes screened. In one of the eleven LCA families, the causative gene/mutation was not identified but many homozygous blocks were noted indicating that a possible novel locus/gene might be involved. The genotype and phenotype features, especially the fundus changes for AIPL1, RPE65, CRB1, RDH12 genes were as reported earlier.

Novel Deletion of SERPINF1 Causes Autosomal Recessive Osteogenesis Imperfecta Type VI in Two Brazilian Families

PubMed Central

Moldenhauer Minillo, Renata; Sobreira, Nara; de Fatima de Faria Soares, Maria; Jurgens, Julie; Ling, Hua; Hetrick, Kurt N.; Doheny, Kimberly F.; Valle, David; Brunoni, Decio; Alvarez Perez, Ana B.

2014-01-01

Autosomal recessive osteogenesis imperfecta (OI) accounts for 10% of all OI cases, and, currently, mutations in 10 genes (CRTAP, LEPRE1, PPIB, SERPINH1, FKBP10, SERPINF1, SP7, BMP1, TMEM38B, and WNT1) are known to be responsible for this form of the disease. PEDF is a secreted glycoprotein of the serpin superfamily that maintains bone homeostasis and regulates osteoid mineralization, and it is encoded by SERPINF1, currently associated with OI type VI (MIM 172860). Here, we report a consanguineous Brazilian family in which multiple individuals from at least 4 generations are affected with a severe form of OI, and we also report an unrelated individual from the same small city in Brazil with a similar but more severe phenotype. In both families the same homozygous SERPINF1 19-bp deletion was identified which is not known in the literature yet. We described intra- and interfamilial clinical and radiological phenotypic variability of OI type VI caused by the same homozygous SERPINF1 19-bp deletion and suggest a founder effect. Furthermore, the SERPINF1 genotypes/phenotypes reported so far in the literature are reviewed. PMID:25565926

A new family programme in Zhejiang province.

PubMed

Xu, B

1994-04-01

Zhejiang Province in China has promoted a new family planning program since April 1993. The program stresses delayed marriage and childbearing, fewer and healthier births, modernization of family life, and prosperity through hard work. The people are receptive to the new program out of a desire for an improved standard of living. The objective is to build small, modern families who 1) practice deferred marriage and childbearing; 2) voluntarily practice family planning and have no unplanned births; 3) practice avoidance of consanguineous marriage, become sterilized if a carrier of a hereditary disease of chromosomal abnormality, and use premarital education and counseling and proper prenatal care; 4) uphold the laws and maintain discipline in action to avoid criminal behavior; 5) establish families that respect the old, care for children, and help their neighbors; 6) complete 9 years of compulsory education; and 7) create well being through hard work. The program is compatible with the strategy of the "three stresses" and an integrated approach. IEC and service provision are important components in program implementation. The target population are the masses and grassroots cadres, particularly those in the childbearing ages. IEC will be directed in different ways to different groups. Those aged 18-35 years will receive education. Face to face interaction with family planning workers and lectures will be directed to grassroots cadres. The mass media will be employed to reach the masses. The messages will include information and persuasion to adopt new families, accept family planning regulations, and learn about contraceptive use, healthy births and childrearing, education, health care, sex education, and income generation skills. Classes will be conducted for groups, such as teenagers, unmarried youth, pregnant women, and lactating women. Priority will be given to couples that accept the certificates for one child; favoritism will be granted for allocation of

Reduced small world brain connectivity in probands with a family history of epilepsy.

PubMed

Bharath, R D; Chaitanya, G; Panda, R; Raghavendra, K; Sinha, S; Sahoo, A; Gohel, S; Biswal, B B; Satishchandra, P

2016-12-01

The role of inheritance in ascertaining susceptibility to epilepsy is well established, although the pathogenetic mechanisms are still not very clear. Interviewing for a positive family history is a popular epidemiological tool in the understanding of this susceptibility. Our aim was to visualize and localize network abnormalities that could be associated with a positive family history in a group of patients with hot water epilepsy (HWE) using resting-state functional magnetic resonance imaging (rsfMRI). Graph theory analysis of rsfMRI (clustering coefficient γ; path length λ; small worldness σ) in probands with a positive family history of epilepsy (FHE+, 25) were compared with probands without FHE (FHE-, 33). Whether a closer biological relationship was associated with a higher likelihood of network abnormalities was also ascertained. A positive family history of epilepsy had decreased γ, increased λ and decreased σ in bilateral temporofrontal regions compared to FHE- (false discovery rate corrected P ≤ 0.0062). These changes were more pronounced in probands having first degree relatives and siblings with epilepsy. Probands with multiple types of epilepsy in the family showed decreased σ in comparison to only HWE in the family. Graph theory analysis of the rsfMRI can be used to understand the neurobiology of diseases like genetic susceptibility in HWE. Reduced small worldness, proportional to the degree of relationship, is consistent with the current understanding that disease severity is higher in closer biological relations. © 2016 EAN.

From new genetics to everyday knowledge: Ideas about how genetic diseases are transmitted in two large Brazilian families

NASA Astrophysics Data System (ADS)

Santos, Silvana; Bizzo, Nelio

2005-07-01

This study focuses on everyday or lay understandings of inheritance. In the northeastern Brazil, 100 individuals were interviewed in order to describe how they explain the origin of genetic disorders affecting their relatives for several generations. There were involved 60 individuals from a large consanguineous family with many members affected with a neurodegenerative disorder, SPOAN syndrome (spastic paraplegia, optic atrophy and neuropathy), and 40 individuals of another family living with neurofibromatosis type 1 (NF1). The results indicate that families here studied have built narratives to explain the origin of genetic diseases, saying that an ancestor infected with syphilis gave rise to disorders and birthmarks transmitted to descendents.

Gender, Work-Family Linkages, and Economic Success among Small Business Owners.

ERIC Educational Resources Information Center

Loscocco, Karyn A.; Leicht, Kevin T.

1993-01-01

Investigated work-family connections and economic success among women and men small business owners. Analyses of data from 3-year panel survey of 99 women and 312 men showed considerable gender similarity in processes through which business and individual characteristics affect personal earnings, although women were disadvantaged in some…

Heterogeneity of the cystic fibrosis phenotype in a large kindred family in Qatar with cystic fibrosis mutation (I1234V).

PubMed

Abdul Wahab, A; Al Thani, G; Dawod, S T; Kambouris, M; Al Hamed, M

2001-04-01

Twenty-nine subjects (17 families) with cystic fibrosis belonging to the same Bedouin tribe were screened for cystic fibrosis transmembrane regulator gene mutations (CFTR). Homozygous I1234V mutation in exon 19 was identified in all families with a relatively high rate of consanguinity (96.6 per cent). The homozygous I1234V mutation tended to present with a variable degree of pulmonary disease, pancreatic insufficiency and electrolyte imbalance. Homozygous I1234V was found to be a common mutation in the studied Bedouin tribe in Qatar.

The Role of a Novel TRMT1 Gene Mutation and Rare GRM1 Gene Defect in Intellectual Disability in Two Azeri Families.

PubMed

Davarniya, Behzad; Hu, Hao; Kahrizi, Kimia; Musante, Luciana; Fattahi, Zohreh; Hosseini, Masoumeh; Maqsoud, Fariba; Farajollahi, Reza; Wienker, Thomas F; Ropers, H Hilger; Najmabadi, Hossein

2015-01-01

Cognitive impairment or intellectual disability (ID) is a widespread neurodevelopmental disorder characterized by low IQ (below 70). ID is genetically heterogeneous and is estimated to affect 1-3% of the world's population. In affected children from consanguineous families, autosomal recessive inheritance is common, and identifying the underlying genetic cause is an important issue in clinical genetics. In the framework of a larger project, aimed at identifying candidate genes for autosomal recessive intellectual disorder (ARID), we recently carried out single nucleotide polymorphism-based genome-wide linkage analysis in several families from Ardabil province in Iran. The identification of homozygosity-by-descent loci in these families, in combination with whole exome sequencing, led us to identify possible causative homozygous changes in two families. In the first family, a missense variant was found in GRM1 gene, while in the second family, a frameshift alteration was identified in TRMT1, both of which were found to co-segregate with the disease. GRM1, a known causal gene for autosomal recessive spinocerebellar ataxia (SCAR13, MIM#614831), encodes the metabotropic glutamate receptor1 (mGluR1). This gene plays an important role in synaptic plasticity and cerebellar development. Conversely, the TRMT1 gene encodes a tRNA methyltransferase that dimethylates a single guanine residue at position 26 of most tRNAs using S-adenosyl methionine as the methyl group donor. We recently presented TRMT1 as a candidate gene for ARID in a consanguineous Iranian family (Najmabadi et al., 2011). We believe that this second Iranian family with a biallelic loss-of-function mutation in TRMT1 gene supports the idea that this gene likely has function in development of the disorder.

Population education for young adults: making the small family desirable.

PubMed

Butt, H

1972-01-01

The approach to population control has been almost totally clinical in India so far. A new program of population education which is broader than the clinical appeal is needed. The major target population in India would be illiterates and those with a small amount of education. Within this target population different groups would have to be treated differently. Division would be between illiterates and literates, between urban and rural populations, and between male and female groups. Family planning must be related to other aspects of life, e.g., the health and well-being of the mother and other children in the family. Sex and social education must be presented together. Basic values cannot be changed. Smaller families will eventually change the values. By concentrating on the basic value of survival of the family, the best method to effect this can be shown to be better care of fewer c hildren rather than proliferation of many children. Education should concentrate on the individual and on economic reasons for limiting family size. Once the idea of limiting family size is accepted, it remains to be shown that methods for doing this are available, safe, and religiously and socially acceptable. The message needs constant repetition. Group education would be least expensive. Population education could be presented by incorporating it into other socioeconomic contexts such as reading classes for the illiterates and mathematics classes for the basic literates.

[Maxillodental anomalies and consanguineous marriages].

PubMed

Garaev, Z I

1999-01-01

Families of 549 probands and families of 123 probands with cleft lip and/or palate were examined in order to evaluate the relationship between marriages between close relatives and the incidence and structure of maxillodental diseases. Clinical and genealogical analysis of families of probands with maxillodental abnormalities and cleft lip and/or palate showed a significantly higher incidence of marriages between close relatives and an inbreeding coefficient in these families. Analysis of the population and familial incidence of maxillodental abnormalities and the inbreeding coefficient will help the physicians consulting such families more accurately evaluate the risk and improve the efficacy of prevention of such conditions.

Out of Sight, Out of Mind: Homeless Children and Families in Small-Town America.

ERIC Educational Resources Information Center

Vissing, Yvonne M.

Homelessness in small towns and rural areas is on the rise, and a substantial portion of the rural homeless consists of families with children. This book draws on interviews and case studies of over 300 homeless children and their families, primarily in New Hampshire, and on supporting statistics to provide individual and sociological perspectives…

Between acculturation and ambivalence: knowledge of genetics and attitudes towards genetic testing in a consanguineous bedouin community.

PubMed

Raz, Aviad E; Atar, Marcela; Rodnay, Maya; Shoham-Vardi, Ilana; Carmi, Rivka

2003-01-01

The Bedouins of the Negev (Southern part of Israel) are a community at increased risk for genetic diseases and congenital anomalies as a result of frequent consanguinity (particularly patrilateral parallel-cousin marriage) and underutilization of prenatal genetic tests due to a Muslim ban on abortion. To assess the knowledge and attitudes of Bedouin schoolchildren and their teachers towards a community-based, premarital carrier-matching program aimed at reducing the prevalence at birth of genetic diseases. A questionnaire was presented to 61 teachers and 40 schoolchildren as part of guided interaction in small groups, conducted in Bedouin schools between 1999 and 2001. Susceptibility as well as knowledge of genetics were found to correlate with a positive attitude towards the genetics program among both teachers and pupils. However, pupils had a lower knowledge index as compared to teachers, and their attitudes were slightly less positive. The difference between teachers and pupils is discussed in the context of the latter's acculturation, which contradicts tradition and parental authority and can generate ambivalence. Attitudes are further discussed in the context of the Health Belief Model and the complex interplay of tradition, Islam, cousin marriage and biomedicine. Copyright 2003 S. Karger AG, Basel

XPC gene mutations in families with xeroderma pigmentosum from Pakistan; prevalent founder effect.

PubMed

Ijaz, Ambreen; Basit, Sulman; Gul, Ajab; Batool, Lilas; Hussain, Abrar; Afzal, Sibtain; Ramzan, Khushnooda; Ahmad, Jamil; Wali, Abdul

2018-03-23

Xeroderma pigmentosum (XP) is a rare autosomal recessive skin disorder characterized by hyperpigmentation, premature skin aging, ocular and cutaneous photosensitivity, and increased risk of skin carcinoma. We investigated seven consanguineous XP families with nine patients from Pakistan. All the Patients exhibited typical clinical symptoms of XP since first year of life. Whole genome SNP genotyping identified a 14 Mb autozygous region segregating with the disease phenotype on chromosome 3p25.1. DNA sequencing of XPC gene revealed a founder homozygous splice site mutation (c.2251-1G>C) in patients from six families (A-F) and a homozygous nonsense mutation (c.1399C>T; p.Gln467*) in patients of family G. This is the first report of XPC mutations, underlying XP phenotype, in Pakistani population. © 2018 Japanese Teratology Society.

Campanulaceae: a family with small seeds that require light for germination

PubMed Central

Koutsovoulou, Katerina; Daws, Matthew I.; Thanos, Costas A.

2014-01-01

Background and Aims The Campanulaceae is a large cosmopolitan family, but is understudied in terms of germination, and seed biology in general. Small seed mass (usually in the range 10–200 µg) is a noteworthy trait of the family, and having small seeds is commonly associated with a light requirement. Thus, the purpose of this study was to investigate the effect of light on germination in 131 taxa of the Campanulaceae family, from all five continents of its distribution. Methods For all taxa, seed germination was tested in light (8 or 12 h photoperiod) and continuous darkness under constant and alternating temperatures. For four taxa, the effect of light on germination was examined over a wide range of temperatures on a thermogradient plate, and the possible substitution of the light requirement by gibberellic acid and nitrate was examined in ten taxa. Key Results For all 131 taxa, seed germination was higher in light than in darkness for every temperature tested. Across species, the light requirement decreased significantly with increasing seed mass. For larger seeded species, germination in the dark reached higher levels under alternating than under constant temperatures. Gibberellic acid promoted germination in darkness whereas nitrates partially substituted for a light requirement only in species showing some dark germination. Conclusions A light requirement for germination, observed in virtually all taxa examined, constitutes a collective characteristic of the family. It is postulated that smaller seeded taxa might germinate only on the soil surface or at shallow depths, while larger seeded species might additionally germinate when buried in the soil if cued to do so by fluctuating temperatures. PMID:24232382

[Juvenile myasthenia gravis in sub-Saharan Africa: a case study of two consanguine sisters born from consanguinity in Togo].

PubMed

Maneh, Nidain; Apetse, Kossivi; Diatewa, Bénédicte Marèbe; Domingo, Sidik Abou-Bakr; Agba, Aidé Isabelle; Ayena, Koffi Didier; Balogou, Koffi Agnon; Balo, Komi Patrice

2017-01-01

Myasthenia gravis is a rare acquired autoimmune pathology causing neuromuscular transmission impairment. Juvenile onset of myasthenia gravis is often characterized by ocular involvement. We report two cases of ocular juvenile myasthenia gravis (JMG) in two siblings. They were two young girls, XA and XB, aged 11 and 9 years, of Malian origin, residing in Togo, born from first-degree of consanguinity presenting to Ophthalmology due to progressive decrease in visual acuity. XA showed visual acuity 8/10 on both eyes while XB showed improvement in visual acuity from 3/10 to 7/10 using a pinhole occluder, suggesting ametropia. XA had a 2-year history of bilateral ptosis lifting the upper eyelid of 7 mm, while XB had a 3-year history of bilateral ptosis with no lifting of the upper eyelid. Ice pack test was strongly positive in both patients. They had Cogan's lid twitch with paresis of the oculomotor nerve without diplopia. The dosage of acetylcholine receptor autoantibodies was normal. The diagnosis of JMG associated with ametropia was suspected. Ametropia was corrected by glasses and a specific treatment with pyridostigmine was initiated, but both patients were lost to follow-up. Autoimmune myasthenia gravis with inaugural ophthalmologic manifestation is rare but it can occur among children living in sub-Saharan Africa. Studies should be conducted to establish the features of this disease.

Intermittent chronic neutropenia in a patient with familial Mediterranean fever.

PubMed

Ganiou Tidjani, K; Ailal, F; Najib, J; Bellanné-Chantelot, C; Donadieu, J; Bousfiha, A A

2008-11-01

A 12-year-old daughter of consanguineous Moroccan parents was diagnosed with cyclic neutropenia, based on a combination of recurrent gingivostomatitis, a fluctuating neutrophil count, and several episodes of severe neutropenia. No ELA2 gene mutations were found. At age 19 years she presented with edema of the limbs, proteinuria and renal failure. Renal amyloidosis AA was diagnosed by biopsy. Gene mutations associated with family Mediterranean fever (FMF) were sought, and a homozygous mutation (M694V) was found in the MFEV gene. This is the novel finding of FMF that masqueraded as cyclic neutropenia. (c) 2008 Wiley-Liss, Inc.

The Role of a Novel TRMT1 Gene Mutation and Rare GRM1 Gene Defect in Intellectual Disability in Two Azeri Families

PubMed Central

Kahrizi, Kimia; Musante, Luciana; Fattahi, Zohreh; Hosseini, Masoumeh; Maqsoud, Fariba; Farajollahi, Reza; Wienker, Thomas F.; Ropers, H. Hilger; Najmabadi, Hossein

2015-01-01

Cognitive impairment or intellectual disability (ID) is a widespread neurodevelopmental disorder characterized by low IQ (below 70). ID is genetically heterogeneous and is estimated to affect 1–3% of the world’s population. In affected children from consanguineous families, autosomal recessive inheritance is common, and identifying the underlying genetic cause is an important issue in clinical genetics. In the framework of a larger project, aimed at identifying candidate genes for autosomal recessive intellectual disorder (ARID), we recently carried out single nucleotide polymorphism-based genome-wide linkage analysis in several families from Ardabil province in Iran. The identification of homozygosity-by-descent loci in these families, in combination with whole exome sequencing, led us to identify possible causative homozygous changes in two families. In the first family, a missense variant was found in GRM1 gene, while in the second family, a frameshift alteration was identified in TRMT1, both of which were found to co-segregate with the disease. GRM1, a known causal gene for autosomal recessive spinocerebellar ataxia (SCAR13, MIM#614831), encodes the metabotropic glutamate receptor1 (mGluR1). This gene plays an important role in synaptic plasticity and cerebellar development. Conversely, the TRMT1 gene encodes a tRNA methyltransferase that dimethylates a single guanine residue at position 26 of most tRNAs using S-adenosyl methionine as the methyl group donor. We recently presented TRMT1 as a candidate gene for ARID in a consanguineous Iranian family (Najmabadi et al., 2011). We believe that this second Iranian family with a biallelic loss-of-function mutation in TRMT1 gene supports the idea that this gene likely has function in development of the disorder. PMID:26308914

[Oral mucosa analog allografts in non-consanguineous rats].

PubMed

González, Luis; Padrón, Karla; Salmen, Siham; Jerez, Elsy; Dávila, Lorena; Solórzano, Eduvigis

2017-01-24

Although there are therapeutic options for the treatment of oral mucosa defects, the need for functional, anatomical and aesthetically similar substitutes persists, as well as for solutions to reduce autologous grafts morbidity. To determine clinical and histological compatibility of equivalent oral mucosa allografts generated through tissue engineering in non-consanguineous rats. We used a sample of oral mucosa from Sprague Dawley rats to obtain a fibroblast culture and a keratinocytes and fibroblasts co-culture. In both cases, we used a commercial collagen membrane as "scaffold". After ten weeks of culture, we grafted the resulting membranes into four Wistar rats. The first phase of the study was the development of the oral mucosa equivalents generated by tissue engineering. Then, we implanted them in immunocompetent Wistar rats, and finallywe evaluated the clinical and histological features of the allografts. In vivo evaluation of mucosal substitutes showed a correct integration of artificial oral mucosa in immunocompetent hosts, with an increase in periodontal biotype and the creation of a zone with increased keratinization. Histologically, the tissue was similar to the control oral mucosa sample with no inflammatory reaction nor clinical or histological rejection signs. The equivalent oral mucosa allografts generated by tissue engineering showed clinical and histological compatibility.

Molecular characterisation of congenital glaucoma in a consanguineous Canadian community: a step towards preventing glaucoma related blindness

PubMed Central

Martin, S; Sutherland, J.; Levin, A.; Klose, R.; Priston, M.; Heon, E.

2000-01-01

Glaucoma is a leading cause of irreversible blindness in Canada. Congenital glaucoma usually manifests during the first years of life and is characterised by severe visual loss and autosomal recessive inheritance. Two disease loci, on chromosomes 1p36 and 2p21, have been associated with various forms of congenital glaucoma. A branch of a large six generation family from a consanguineous Amish community in south western Ontario was affected with congenital glaucoma and was studied by linkage and mutational analysis to identify the glaucoma related genetic defects. Linkage analysis using the MLINK component of the LINKAGE package (v 5.1) showed evidence of linkage to the 2p21 region (Zmax=3.34, θ=0, D2S1348 and D2S1346). Mutational analysis of the primary candidate gene, CYP1B1, was done by direct cycle sequencing, dideoxy fingerprinting analysis, and fragment analysis. Two different disease causing mutations in exon 3, 1410del13 and 1505G→A, both segregated with the disease phenotype. The two different combinations of these alleles appeared to result in a variable expressivity of the phenotype. The compound heterozygote appeared to have a milder phenotype when compared to the homozygotes for the 13 bp deletion. The congenital glaucoma phenotype for this large inbred Amish family is the result of mutations in CYP1B1 (2p21). The molecular information derived from this study will be used to help identify carriers of the CYP1B1 mutation in this community and optimise the management of those at risk of developing glaucoma.


Keywords: congenital glaucoma; CYP1B1; gene; genetic counselling PMID:10851252

Identification of a novel homozygous mutation Arg459Pro in SYNJ1 gene of an Indian family with autosomal recessive juvenile Parkinsonism.

PubMed

Kirola, Laxmi; Behari, Madhuri; Shishir, Chandan; Thelma, B K

2016-10-01

A novel homozygous missense mutation (c.773G > A, p.Arg258Gln) in Synaptojanin 1 (SYNJ1, 21q22.2) has recently been reported in two Italian and one Iranian consanguineous families with autosomal recessive juvenile Parkinsonism (ARJP). Contribution of this synaptic gene related to Parkinsonism phenotypes in other populations still remains unidentified. An ARJP family with two affected siblings characterized by frequent tremor with bradykinesia and rigidity was recruited in this study. Both siblings showed intense dyskinesia and dystonia on administration of Syndopa. The family was analyzed for both mutations and exon dosage variations in PARKIN, PINK1 and DJ1. Further, whole exome sequencing was performed in two affected and one unaffected sibling in the family. We identified a novel homozygous mutation (c.1376C > G, p.Arg459Pro) in SYNJ1 segregating in this family. This p.Arg459Pro mutation was not observed in 285 additional Parkinson disease (PD) samples (32 familial, 81 early onset and 172 late onset) screened by PCR-Sanger-sequencing. It was also absent in dbSNP, 1000 Genomes, ExAC, NHLBI-ESP database and in >250 ethnically matched exomes available in our laboratory. The arginine residue is highly conserved across species and predicted to be damaging by several in silico tools. As with the previous mutation p.Arg258Gln, p.Arg459Pro is also present in Sac 1 domain of SYNJ1 wherein p.Arg258Gln mutation has already been described to impair the phosphatase activity. We report another novel mutation in SYNJ1 of an Indian consanguineous ARJP family. Finding an additional mutation in this gene further supports the involvement of SYNJ1 in PD pathogenesis across different ethnicities. Copyright © 2016 Elsevier Ltd. All rights reserved.

Family genome browser: visualizing genomes with pedigree information.

PubMed

Juan, Liran; Liu, Yongzhuang; Wang, Yongtian; Teng, Mingxiang; Zang, Tianyi; Wang, Yadong

2015-07-15

Families with inherited diseases are widely used in Mendelian/complex disease studies. Owing to the advances in high-throughput sequencing technologies, family genome sequencing becomes more and more prevalent. Visualizing family genomes can greatly facilitate human genetics studies and personalized medicine. However, due to the complex genetic relationships and high similarities among genomes of consanguineous family members, family genomes are difficult to be visualized in traditional genome visualization framework. How to visualize the family genome variants and their functions with integrated pedigree information remains a critical challenge. We developed the Family Genome Browser (FGB) to provide comprehensive analysis and visualization for family genomes. The FGB can visualize family genomes in both individual level and variant level effectively, through integrating genome data with pedigree information. Family genome analysis, including determination of parental origin of the variants, detection of de novo mutations, identification of potential recombination events and identical-by-decent segments, etc., can be performed flexibly. Diverse annotations for the family genome variants, such as dbSNP memberships, linkage disequilibriums, genes, variant effects, potential phenotypes, etc., are illustrated as well. Moreover, the FGB can automatically search de novo mutations and compound heterozygous variants for a selected individual, and guide investigators to find high-risk genes with flexible navigation options. These features enable users to investigate and understand family genomes intuitively and systematically. The FGB is available at http://mlg.hit.edu.cn/FGB/. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Consanguinity and recurrence risk of stillbirth and infant death.

PubMed Central

Stoltenberg, C; Magnus, P; Skrondal, A; Lie, R T

1999-01-01

OBJECTIVES: The aim of this study was to estimate the recurrence risk for stillbirth and infant death and compare results for offspring of first-cousin parents with results for offspring of unrelated parents. METHODS: The study population consisted of all single births with a previous sibling born in Norway between 1967 and 1994. Altogether, 629,888 births were to unrelated parents, and 3466 births were to parents who were first cousins. The risk of stillbirth and infant death was estimated for subsequent siblings contingent on parental consanguinity and survival of the previous sibling. RESULTS: For unrelated parents, the risk of early death (stillbirth plus infant death) for the subsequent sibling was 17 of 1000 if the previous child survived and 67 of 1000 if the previous child died before 1 year of age. For parents who were first cousins, the risk of early death for the subsequent sibling was 29 of 1000 if the previous child survived and 116 of 1000 if the previous child died. CONCLUSIONS: The risk of recurrence of stillbirth and infant death is higher for offspring of first-cousin parents compared with offspring of unrelated parents. PMID:10191794

Familial epilepsy in Algeria: Clinical features and inheritance profiles.

PubMed

Chentouf, Amina; Dahdouh, Aïcha; Guipponi, Michel; Oubaiche, Mohand Laïd; Chaouch, Malika; Hamamy, Hanan; Antonarakis, Stylianos E

2015-09-01

To document the clinical characteristics and inheritance pattern of epilepsy in multigeneration Algerian families. Affected members from extended families with familial epilepsy were assessed at the University Hospital of Oran in Algeria. Available medical records, neurological examination, electroencephalography and imaging data were reviewed. The epilepsy type was classified according to the criteria of the International League Against Epilepsy and modes of inheritance were deduced from pedigree analysis. The study population included 40 probands; 23 male (57.5%) and 17 female subjects (42.5%). The mean age of seizure onset was 9.5 ± 6.1 years. According to seizure onset, 16 patients (40%) had focal seizures and 20 (50%) had generalized seizures. Seizure control was achieved for two patients (5%) for 10 years, while 28 (70%) were seizure-free for 3 months. Eleven patients (27.5%) had prior febrile seizures, 12 were diagnosed with psychiatric disorders and four families had syndromic epilepsy. The consanguinity rate among parents of affected was 50% with phenotypic concordance observed in 25 families (62.5%). Pedigree analysis suggested autosomal dominant (AD) inheritance with or without reduced penetrance in 18 families (45%), probable autosomal recessive (AR) inheritance in 14 families (35%), and an X-linked recessive inheritance in one family. This study reveals large Algerian families with multigenerational inheritance of epilepsy. Molecular testing such as exome sequencing would clarify the genetic basis of epilepsy in some of our families. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Small Family, Smart Family? Family Size and the IQ Scores of Young Men

ERIC Educational Resources Information Center

Black, Sandra E.; Devereux, Paul J.; Salvanes, Kjell G.

2010-01-01

This paper uses Norwegian data to estimate the effect of family size on IQ scores of men. Instrumental variables (IV) estimates using sex composition as an instrument show no significant negative effect of family size; however, IV estimates using twins imply that family size has a negative effect on IQ scores. Our results suggest that the effect…

Disease severity in familial cases of IBD.

PubMed

Andreu, M; Márquez, L; Domènech, E; Gisbert, J P; García, V; Marín-Jiménez, I; Peñalva, M; Gomollón, F; Calvet, X; Merino, O; Garcia-Planella, E; Vázquez-Romero, N; Esteve, M; Nos, P; Gutiérrez, A; Vera, I; Cabriada, J L; Martín, M D; Cañas-Ventura, A; Panés, J

2014-03-01

Phenotypic traits of familial IBD relative to sporadic cases are controversial, probably related to limited statistical power of published evidence. To know if there are phenotype differences between familial and sporadic IBD, evaluating the prospective Spanish registry (ENEIDA) with 11,983 cases. 5783 patients (48.3%) had ulcerative colitis (UC) and 6200 (51.7%) Crohn's disease (CD). Cases with one or more 1st, 2nd or 3rd degree relatives affected by UC/CD were defined as familial case. In UC and CD, familial cases compared with sporadic cases had an earlier disease onset (UC: 33 years [IQR 25-44] vs 37 years [IQR 27-49]; p<0.0001); (CD: 27 years [IQR 21-35] vs 29 years [IQR 22-40]; p<0.0001), higher prevalence of extraintestinal immune-related manifestations (EIMs) (UC: 17.2% vs 14%; p=0.04); (CD: 30.1% vs 23.6%; p<0.0001). Familial CD had higher percentage of ileocolic location (42.7% vs 51.8%; p=0.0001), penetrating behavior (21% vs 17.6%; p=0.01) and perianal disease (32% vs 27.1%; p=0.003). Differences are not influenced by degree of consanguinity. When a sufficiently powered cohort is evaluated, familial aggregation in IBD is associated to an earlier disease onset, more EIMs and more severe phenotype in CD. This feature should be taken into account at establishing predictors of disease course. © 2013.

Age-standardized Incidence Rates for Leukemia Associated with Consanguineous Marriages in 68 Countries, an Ecological Study

PubMed Central

Saadat, Mostafa

2015-01-01

Consanguineous marriage that defines as a union between biologically related persons has a variety of known deleterious correlations with factors that affect public health within human populations. To investigate the association between the mean of inbreeding coefficient (α) and incidence of leukemia, the present ecological study on 68 countries was carried out. Statistical analysis showed that the age-standardized incidence rate of leukemia positively correlated with log10GNI per capita (r=0.699, df=66, P<0.001) and negatively correlated with log10α (r=−0.609, df=66, P<0.001). Controlling log10GNI per capita, a significant negative correlation between log10α and the age-standardized incidence rate of leukemia was observed (r=−0.392, df=65, P=0.001). The countries were stratified according to their annual GNI per capita, low and high-income countries with GNI per capita less than and more than 10,000$, respectively. Statistical analysis showed that in high-income countries, after controlling for log10GNI per capita, the correlation between the age-standardized incidence rate of leukemia and log10α was still significant (r=−0.600, df=36, P<0.001). It should be noted that there was no significant association between the age-standardized mortality rate due to leukemia and log10α (P>0.05). The present finding indicates that the rate of leukemia, age-standardized for incidence, is lower in countries with a high prevalence of consanguineous marriages. PMID:25960855

Primary Immunodeficiency Diseases in Highly Consanguineous Populations from Middle East and North Africa: Epidemiology, Diagnosis, and Care

PubMed Central

Al-Mousa, Hamoud; Al-Saud, Bandar

2017-01-01

Middle East and North Africa region (MENA)1 populations are of different ethnic origins. Consanguineous marriages are common practice with an overall incidence ranging between 20 and 50%. Primary immunodeficiency diseases (PIDs) are a group of heterogeneous genetic disorders caused by defects in the immune system that predisposes patients to recurrent infections, autoimmune diseases, and malignancies. PIDs are more common in areas with high rates of consanguineous marriage since most have an autosomal recessive mode of inheritance. Studies of PIDs in the region had contributed into the discovery and the understanding of several novel immunodeficiency disorders. Few MENA countries have established national registries that helped in estimating the prevalence and defining common PID phenotypes. Available reports from those registries suggest a predominance of combined immunodeficiency disorders in comparison to antibody deficiencies seen in other populations. Access to a comprehensive clinical immunology management services is limited in most MENA countries. Few countries had established advanced clinical immunology service, capable to provide extensive genetic testing and stem cell transplantation for various immunodeficiency disorders. Newborn screening for PIDs is an essential need in this population considering the high incidence of illness and can be implemented and incorporated into existing newborn screening programs in some MENA countries. Increased awareness, subspecialty training in clinical immunology, and establishing collaborating research centers are necessary to improve patient care. In this review, we highlight some of the available epidemiological data, challenges in establishing diagnosis, and available therapy for PID patients in the region. PMID:28694805

A Quick Test on Rotation Period Clustering for the Small Members of the Koronis Family

NASA Astrophysics Data System (ADS)

Chang, Chan-Kao; Lin, Hsing-Wen; Ip, Wing-Huen

2016-01-01

Rotation period clustering in prograde/retrograde rotators might be the preliminary indication of the Slivan state in the Koronis family as a result of the Yarkovsky-O’Keefe-Radzievskii-Paddack effect. We follow the general scenario of dispersion in the semimajor axis of the asteroid family members to separate prograde and retrograde rotators in the Koronis family. From the available rotation periods obtained from PTF/iPTF, we were unable to find the rotation period clustering of objects with H ≳ 12 mag in the Koronis family. This could be the result of the intermittent collisional process of small asteroids (D ≲ 20 km) which leads to astray Yarkovsky drifting. Measurement of the pole orientations of our sample will verify our preliminary result and validate our method.

Intra-Family Gamete Donation: A Solution to Concerns Regarding Gamete Donation in China?

PubMed

Liao, Juhong; Devolder, Katrien

2016-09-01

Gamete donation from third parties is controversial in China as it severs blood ties, which are considered of utmost importance in Confucian tradition. In recent years, infertile couples are increasingly demonstrating a preference for the use of gametes donated by family members to conceive children-known as "intra-family gamete donation." The main advantage of intra-family gamete donation is that it maintains blood ties between children and both parents. To date there is no practice of intra-family gamete donation in China. In this paper, we investigate intra-family adoption in China in order to illustrate that intra-family gamete donation is consistent with Confucian tradition regarding the importance of maintaining blood ties within the family. There are several specific ethical issues raised by intra-family gamete donation. It may, for example, result in consanguinity and the semblance of incest, lead to confused family relationships, and raise concerns about possible coercion of familial donors. Confucian tradition provides a new approach to understand and deal with these ethical issues in a way that Western tradition does not. As a result, we suggest intra-family gamete donation could be an acceptable solution to the problem of infertility in China. However, further discussion and open debates on the ethical issues raised by intra-family gamete donation are needed in China.

Small Science: Infants and Toddlers Experiencing Science in Everyday Family Life

NASA Astrophysics Data System (ADS)

Sikder, Shukla; Fleer, Marilyn

2015-06-01

Vygotsky (1987) stated that the restructured form of everyday concepts learned at home and in the community interact with scientific concepts introduced in formal school settings, leading to a higher level of scientific thinking for school-aged children. But, what does this mean for the scientific learning of infants and toddlers? What kinds of science learning are afforded at home during this early period of life? The study reported in this paper sought to investigate the scientific development of infants-toddlers (10 to 36 months) growing up in Bangladeshi families living in Australia and Singapore. Four families were studied over 2 years. Digital video observations were made of everyday family life and analysed using Vygotsky's theoretical framework of everyday concepts and scientific concepts (51 h of digital observations). While there are many possibilities for developing scientific concepts in infants-toddlers' everyday life, our study found four categories of what we have called small science: multiple possibilities for science; discrete science; embedded science and counter intuitive science. The findings of this study contribute to the almost non-existent literature into infants and toddlers' scientific development and advance new understandings of early childhood science education.

A novel COL4A3 mutation causes autosomal-recessive Alport syndrome in a large Turkish family.

PubMed

Uzak, Asli Subasioglu; Tokgoz, Bulent; Dundar, Munis; Tekin, Mustafa

2013-03-01

Alport syndrome (AS) is a genetically heterogeneous disorder that is characterized by hematuria, progressive renal failure typically resulting in end-stage renal disease, sensorineural hearing loss, and variable ocular abnormalities. Only 15% of cases with AS are autosomal recessive and are caused by mutations in the COL4A3 or COL4A4 genes, encoding type IV collagen. Clinical data in a large consanguineous family with four affected members were reviewed, and genomic DNA was extracted. For mapping, 15 microsatellite markers flanking COL4A3, COL4A4, and COL4A5 in 16 family members were typed. For mutation screening, all coding exons of COL4A3 were polymerase chain reaction- amplified and Sanger-sequenced from genomic DNA. The disease locus was mapped to chromosome 2q36.3, where COL4A3 and COL4A4 reside. Sanger sequencing revealed a novel mis-sense mutation (c.2T>C; p.M1T) in exon 1 of COL4A3. The identified nucleotide change was not found in 100 healthy ethnicity-matched controls via Sanger sequencing. We present a large consanguineous Turkish family with AS that was found to have a COL4A3 mutation as the cause of the disease. Although the relationship between the various genotypes and phenotypes in AS has not been fully elucidated, detailed clinical and molecular analyses are helpful for providing data to be used in genetic counseling. It is important to identify new mutations to clarify their clinical importance, to assess the prognosis of the disease, and to avoid renal biopsy for final diagnosis.

A novel RLBP1 gene geographical area-related mutation present in a young patient with retinitis punctata albescens.

PubMed

Scimone, Concetta; Donato, Luigi; Esposito, Teresa; Rinaldi, Carmela; D'Angelo, Rosalia; Sidoti, Antonina

2017-08-01

Autosomal recessive forms of retinitis punctata albescens (RPA) have been described. RPA is characterized by progressive retinal degeneration due to alteration in visual cycle and consequent deposit of photopigments in retinal pigment epithelium. Five loci have been linked to RPA onset. Among these, the retinaldehyde-binding protein 1 gene, RLBP1, is the most frequently involved and several founder mutations were reported. We report results of a genetic molecular investigation performed on a large Sicilian family in which appears a young woman with RPA. The proband is in homozygous condition for a novel RLBP1 single-pair deletion, and her healthy parents, both heterozygous, are not consanguineous. Thenovelc.398delC (p.P133Qfs*258) involves the exon 6 and leads to a premature stop codon, resulting in a truncated protein entirely missing of CRAL-TRIO lipid-binding domain. Pedigree analysis showed other non-consanguineous relatives heterozygous for the same mutation in the family. Extension of mutation research in the native town of the proband revealed its presence also in healthy subjects, in a heterozygous condition. A novel RLBP1 truncating mutation was detected in a young girl affected by RPA. Although her parents are not consanguineous, the mutation was observed in a homozygous condition. Being them native of the same small Sicilian town of Fiumedinisi, the hypothesis of a geographical area-related mutation was assessed and confirmed.

A Clinical and Molecular Genetic Study of 50 Families with Autosomal Recessive Parkinsonism Revealed Known and Novel Gene Mutations.

PubMed

Taghavi, Shaghayegh; Chaouni, Rita; Tafakhori, Abbas; Azcona, Luis J; Firouzabadi, Saghar Ghasemi; Omrani, Mir Davood; Jamshidi, Javad; Emamalizadeh, Babak; Shahidi, Gholam Ali; Ahmadi, Mona; Habibi, Seyed Amir Hassan; Ahmadifard, Azadeh; Fazeli, Atena; Motallebi, Marzieh; Petramfar, Peyman; Askarpour, Saeed; Askarpour, Shiva; Shahmohammadibeni, Hossein Ali; Shahmohammadibeni, Neda; Eftekhari, Hajar; Shafiei Zarneh, Amir Ehtesham; Mohammadihosseinabad, Saeed; Khorrami, Mehdi; Najmi, Safa; Chitsaz, Ahmad; Shokraeian, Parasto; Ehsanbakhsh, Hossein; Rezaeidian, Jalal; Ebrahimi Rad, Reza; Madadi, Faranak; Andarva, Monavvar; Alehabib, Elham; Atakhorrami, Minoo; Mortazavi, Seyed Erfan; Azimzadeh, Zahra; Bayat, Mahdis; Besharati, Amir Mohammad; Harati-Ghavi, Mohammad Ali; Omidvari, Samareh; Dehghani-Tafti, Zahra; Mohammadi, Faraz; Mohammad Hossein Pour, Banafsheh; Noorollahi Moghaddam, Hamid; Esmaili Shandiz, Ehsan; Habibi, Arman; Taherian-Esfahani, Zahra; Darvish, Hossein; Paisán-Ruiz, Coro

2018-04-01

In this study, the role of known Parkinson's disease (PD) genes was examined in families with autosomal recessive (AR) parkinsonism to assist with the differential diagnosis of PD. Some families without mutations in known genes were also subject to whole genome sequencing with the objective to identify novel parkinsonism-related genes. Families were selected from 4000 clinical files of patients with PD or parkinsonism. AR inheritance pattern, consanguinity, and a minimum of two affected individuals per family were used as inclusion criteria. For disease gene/mutation identification, multiplex ligation-dependent probe amplification, quantitative PCR, linkage, and Sanger and whole genome sequencing assays were carried out. A total of 116 patients (50 families) were examined. Fifty-four patients (46.55%; 22 families) were found to carry pathogenic mutations in known genes while a novel gene, not previously associated with parkinsonism, was found mutated in a single family (2 patients). Pathogenic mutations, including missense, nonsense, frameshift, and exon rearrangements, were found in Parkin, PINK1, DJ-1, SYNJ1, and VAC14 genes. In conclusion, variable phenotypic expressivity was seen across all families.

Debunking Occam's razor: Diagnosing multiple genetic diseases in families by whole-exome sequencing.

PubMed

Balci, T B; Hartley, T; Xi, Y; Dyment, D A; Beaulieu, C L; Bernier, F P; Dupuis, L; Horvath, G A; Mendoza-Londono, R; Prasad, C; Richer, J; Yang, X-R; Armour, C M; Bareke, E; Fernandez, B A; McMillan, H J; Lamont, R E; Majewski, J; Parboosingh, J S; Prasad, A N; Rupar, C A; Schwartzentruber, J; Smith, A C; Tétreault, M; Innes, A M; Boycott, K M

2017-09-01

Recent clinical whole exome sequencing (WES) cohorts have identified unanticipated multiple genetic diagnoses in single patients. However, the frequency of multiple genetic diagnoses in families is largely unknown. We set out to identify the rate of multiple genetic diagnoses in probands and their families referred for analysis in two national research programs in Canada. We retrospectively analyzed WES results for 802 undiagnosed probands referred over the past 5 years in either the FORGE or Care4Rare Canada WES initiatives. Of the 802 probands, 226 (28.2%) were diagnosed based on mutations in known disease genes. Eight (3.5%) had two or more genetic diagnoses explaining their clinical phenotype, a rate in keeping with the large published studies (average 4.3%; 1.4 - 7.2%). Seven of the 8 probands had family members with one or more of the molecularly diagnosed diseases. Consanguinity and multisystem disease appeared to increase the likelihood of multiple genetic diagnoses in a family. Our findings highlight the importance of comprehensive clinical phenotyping of family members to ultimately provide accurate genetic counseling. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

657del5 mutation in the NBS1 gene is associated with Nijmegen breakage syndrome in a Turkish family.

PubMed

Tekin, Mustafa; Doğu, F; Taçyíldiz, N; Akar, E; Ikincioğullari, A; Oğur, G; Yavuz, G; Babacan, E; Akar, N

2002-07-01

We report on a consanguineous Turkish family whose first son died of anal atresia and whose second son presented with severe pre- and post-natal growth retardation as well as striking microcephaly, immunodeficiency, congenital heart disease, chromosomal instability and rhabdomyosarcoma in the anal region. The proband was found to carry the homozygous 657del5 mutation in the NBS1 gene, which is responsible for Nijmegen breakage syndrome (NBS) in most of the Slav populations. Our family, the first diagnosed with NBS in the Turkish population, represents one of the most severely affected examples of the syndrome, with profound pre- and post-natal growth retardation associated with structural abnormalities, and expands the clinical spectrum of this rare disorder.

Rare intracranial cholesterol deposition and a homozygous mutation of LDLR in a familial hypercholesterolemia patient.

PubMed

Li, Haoxian; Zhang, Yanghui; Wei, Xianda; Peng, Ying; Yang, Pu; Tan, Hu; Chen, Chen; Pan, Qian; Liang, Desheng; Wu, Lingqian

2015-09-15

Familial hypercholesterolemia (FH MIM# 143890) is one of the most common autosomal inherited diseases. FH is characterized by elevated plasma levels of total cholesterol and low-density lipoprotein-cholesterol. Mutation in the LDLR gene, which encodes the LDL receptor protein, is responsible for most of the morbidity of FH. The incidence of heterozygous FH is about 1/500, whereas the incidence of homozygous FH is only 1/1,000,000 in Caucasian population. In this study, we report a homozygous LDLR mutation (c.298G>A) in a familial hypercholesterolemia patient, who exhibited intracranial cholesterol deposition, which is a rare addition to the common FH phenotypes. The proband's consanguineous parents have the same heterozygous mutation with elevated concentrations of LDL-C but no xanthoma. Copyright © 2015 Elsevier B.V. All rights reserved.

Identification of two new mutations in the GPR98 and the PDE6B genes segregating in a Tunisian family.

PubMed

Hmani-Aifa, Mounira; Benzina, Zeineb; Zulfiqar, Fareeha; Dhouib, Houria; Shahzadi, Amber; Ghorbel, Abdelmonem; Rebaï, Ahmed; Söderkvist, Peter; Riazuddin, Sheikh; Kimberling, William J; Ayadi, Hammadi

2009-04-01

Autosomal recessive retinitis pigmentosa (ARRP) is a genetically heterogeneous disorder. ARRP could be associated with extraocular manifestations that define specific syndromes such as Usher syndrome (USH) characterized by retinal degeneration and congenital hearing loss (HL). The USH type II (USH2) associates RP and mild-to-moderate HL with preserved vestibular function. At least three genes USH2A, the very large G-protein-coupled receptor, GPR98, and DFNB31 are responsible for USH2 syndrome. Here, we report on the segregation of non-syndromic ARRP and USH2 syndrome in a consanguineous Tunisian family, which was previously used to define USH2B locus. With regard to the co-occurrence of these two different pathologies, clinical and genetic reanalysis of the extended family showed (i) phenotypic heterogeneity within USH2 patients and (ii) excluded linkage to USH2B locus. Indeed, linkage analysis disclosed the cosegregation of the USH2 phenotype with the USH2C locus markers, D5S428 and D5S618, whereas the ARRP perfectly segregates with PDE6B flanking markers D4S3360 and D4S2930. Molecular analysis revealed two new missense mutations, p.Y6044C and p.W807R, occurring in GPR98 and PDE6B genes, respectively. In conclusion, our results show that the USH2B locus at chromosome 3p23-24.2 does not exist, and we therefore withdraw this locus designation. The combination of molecular findings for GPR98 and PDE6B genes enable us to explain the phenotypic heterogeneity and particularly the severe ocular affection first observed in one USH2 patient. This report presents an illustration of how consanguinity could increase familial clustering of multiple hereditary diseases within the same family.

A Small Library in Family Planning.

ERIC Educational Resources Information Center

Planned Parenthood Federation of America, Inc., New York, NY.

This annotated listing of books is intended as a reference for anyone seeking an authoritative introduction to population and family planning information, as a world, family, or individual concern. For each entry, the International Standard Book Number (ISBN) is provided if available. The number preceding each reference represents the…

A novel founder MYO15A frameshift duplication is the major cause of genetic hearing loss in Oman.

PubMed

Palombo, Flavia; Al-Wardy, Nadia; Ruscone, Guido Alberto Gnecchi; Oppo, Manuela; Kindi, Mohammed Nasser Al; Angius, Andrea; Al Lamki, Khalsa; Girotto, Giorgia; Giangregorio, Tania; Benelli, Matteo; Magi, Alberto; Seri, Marco; Gasparini, Paolo; Cucca, Francesco; Sazzini, Marco; Al Khabori, Mazin; Pippucci, Tommaso; Romeo, Giovanni

2017-02-01

The increased risk for autosomal recessive disorders is one of the most well-known medical implications of consanguinity. In the Sultanate of Oman, a country characterized by one of the highest rates of consanguineous marriages worldwide, prevalence of genetic hearing loss (GHL) is estimated to be 6/10 000. Families of GHL patients have higher consanguinity rates than the general Omani population, indicating a major role for recessive forms. Mutations in GJB2, the most commonly mutated GHL gene, have been sporadically described. We collected 97 DNA samples of GHL probands, affected/unaffected siblings and parents from 26 Omani consanguineous families. Analyzing a first family by whole-exome sequencing, we identified a novel homozygous frameshift duplication (c.1171_1177dupGCCATCT) in MYO15A, the gene linked to the deafness locus DFNB3. This duplication was then found in a total of 8/26 (28%) families, within a 849 kb founder haplotype. Reconstruction of haplotype structure at MYO15A surrounding genomic regions indicated that the founder haplotype branched out in the past two to three centuries from a haplotype present worldwide. The MYO15A duplication emerges as the major cause of GHL in Oman. These findings have major implications for the design of GHL diagnosis and prevention policies in Oman.

Affinal and Consanguineal Kin as a Social Support for the Rural Elderly. Paper of the Journal Series of the North Carolina Agricultural Research Service, Raleigh, NC.

ERIC Educational Resources Information Center

Kivett, Vira R.

Although the support network of elderly individuals has received increased attention recently, most research has focused on the parent child relationship without examining other levels of kin interrelations. To examine the help received by rural-transitional older adults from their consanguineous kin (adult children, grandchildren, siblings,…

Relationship between the depression status of patients with resectable non-small cell lung cancer and their family members in China.

PubMed

Wu, Xian-Ning; Su, Dan; Li, Hui-Ping; Wang, Wei-Li; Wu, Wei-Qin; Yang, Ya-Juan; Yu, Feng-Lei; Zhang, Jing-Ping

2013-10-01

Less work on depression status has been done with family members of patients with non-small cell lung cancer (NSCLC). This study investigated depression status of patients and their family members; and the relationship of the depression status between these two groups. This cross-sectional study enrolled 194 patients diagnosed with non-small cell lung cancer as well as their family members. In this study, a self-administered General Information Questionnaire was used to collect general information and the Self-rating Depression Scale (SDS) to assess depression status. Linear correlation analysis was used to probe the relationship of the depression status between patients and their family members. Of the 194 patients, 148 (76.3%) showed symptoms of depression. 148 (76.3%) family members had depression symptoms. The severity of depression in patients was positively correlated with that of family members (r = 0.577, p < 0.01). Patients with lung cancer and their family members suffered depression, and the two were correlated. A prospective study might prove helpful in determining the real relationship existing between the two groups' mental status and whether early detection and intervention might ameliorate this current situation. Copyright © 2013 Elsevier Ltd. All rights reserved.

A 5-year survey of biopsy proven kidney diseases in Lebanon: significant variation in prevalence of primary glomerular diseases by age, population structure and consanguinity

PubMed Central

Karnib, Hussein H.; Gharavi, Ali G.; Aftimos, Georges; Mahfoud, Ziyad; Saad, Reem; Gemayel, Elias; Masri, Badiaa; Assaad, Shafika; Badr, Kamal F.; Ziyadeh, Fuad N.

2010-01-01

Background. Differences in epidemiology of kidney disease across the Middle East may arise from variations in indication for biopsy, environmental exposure and socio-economic status. The Lebanese population is composed of different ethnicities, with distinct ancestry and religion, enabling comparison of their effect on the prevalence of kidney disease within a confined geographic setting and uniform practices. Here we report 5 years’ detailed epidemiology of renal diseases, based on histological diagnosis, in a sample from three large pathology centres in Lebanon. Methods. Records of renal biopsies analysed at the American University of Beirut Medical Center, Hotel Dieu de France Hospital and the Institut National de Pathologie from January 2003 till December 2007 were retrospectively examined. We recorded the following data for each patient: age, gender, indication for renal biopsy and histopathological diagnosis. Religious affiliation and parents’ consanguinity were recorded when feasible. Results. The mean age at renal biopsy was 36.76 ± 20 years (range 1–84). The most common diagnosis was mesangioproliferative glomerulonephritis (GN; 20%), followed by focal segmental glomerulosclerosis (13.2%). While there were no differences in age, gender or indications for biopsy among different religious affiliations, mesangioproliferative GN was significantly more frequent among Muslims (P = 0.039) and offspring of consanguineous unions (P = 0.036). On the other hand, focal segmental glomerulosclerosis was most prevalent in Christians (P < 0.001). Conclusions. Variation in the distribution of diagnoses between Muslim and Christian groups likely reflects differences in population structure and ancestry. In particular, the increased prevalence of mesangioproliferative GN among offspring of consanguineous unions in Muslims suggests a recessive genetic component to this disease which may be identified via homozygosity mapping. These findings have important

Contribution of family labour to the profitability and competitiveness of small-scale dairy production systems in central Mexico.

PubMed

Posadas-Domínguez, Rodolfo Rogelio; Arriaga-Jordán, Carlos Manuel; Martínez-Castañeda, Francisco Ernesto

2014-01-01

The objective of this work was to determine the effect of family labour on the profitability and competitiveness of small-scale dairy farms in the highlands of Central Mexico. Economic data from 37 farms were analysed from a stratified statistical sampling with a Neyman assignment. Three strata were defined taking herd size as criterion. Stratum 1: herds from 3 to 9 cows plus replacements, Stratum 2: herds from 10 to 19 cows and Stratum 3: herds from 20 to 30 cows. The policy analysis matrix was used as the method to determine profitability and competitiveness. The coefficient of private profitability (CPP) when the economic cost of family labour is included in the cost structure was 8.0 %, 31.0 % and 46.0 %. When the economic cost of family labour is not included, CPP increase to 47.0 %, 57.0 % and 66.0 % for each strata, respectively. The private cost ratio (PCR) when family labour is included was 0.79, 0.51 and 0.42 for strata 1, 2 and 3, respectively. When family labour is not included, the PCR was 0.07, 0.25 and 0.26. Net profit per litre of milk including family labour was US$0.03 l(-1) for Stratum 1, US$0.09 for Stratum 2 and US$0.12 l(-1) for Stratum 3; but increased to $0.12, 0.14 and 0.15, respectively, when the economic cost of family labour is not included. It is concluded that family labour is a crucial factor in the profitability and competitiveness of small-scale dairy production.

Homozygous TREM2 mutation in a family with atypical frontotemporal dementia.

PubMed

Le Ber, Isabelle; De Septenville, Anne; Guerreiro, Rita; Bras, José; Camuzat, Agnès; Caroppo, Paola; Lattante, Serena; Couarch, Philippe; Kabashi, Edor; Bouya-Ahmed, Kawtar; Dubois, Bruno; Brice, Alexis

2014-10-01

TREM2 mutations were first identified in Nasu-Hakola disease, a rare autosomal recessive disease characterized by recurrent fractures because of bone cysts and presenile dementia. Recently, homozygous and compound heterozygous TREM2 mutations were identified in rare families with frontotemporal lobar degeneration (FTLD) but without bone involvement. We identified a p.Thr66Met heterozygous mutation in a new consanguineous Italian family. Two sibs had early onset autosomal recessive FTLD without severe bone disorders. Atypical signs were present in this family: early parietal and hippocampus involvement, parkinsonism, epilepsy, and corpus callosum thickness on brain magnetic resonance imaging. This study further demonstrates the implication of TREM2 mutations in FTLD phenotypes. It illustrates the variability of bone phenotype and underlines the frequency of atypical signs in TREM2 carriers. This and previous studies evidence that TREM2 mutation screening should be limited to autosomal recessive FTLD with atypical phenotypes characterized by: (1) a very young age at onset (20-50 years); (2) early parietal and hippocampal deficits; (3) the presence of seizures and parkinsonism; (4) suggestive extensive white matter lesions and corpus callosum thickness on brain magnetic resonance imaging. Copyright © 2014 Elsevier Inc. All rights reserved.

Homozygous TREM2 mutation in a family with atypical frontotemporal dementia

PubMed Central

Bras, José; Camuzat, Agnès; Caroppo, Paola; Lattante, Serena; Couarch, Philippe; Kabashi, Edor; Bouya-Ahmed, Kawtar; Dubois, Bruno; Brice, Alexis

2014-01-01

TREM2 mutations were first identified in Nasu-Hakola disease, a rare autosomal recessive disease characterized by recurrent fractures because of bone cysts and presenile dementia. Recently, homozygous and compound heterozygous TREM2 mutations were identified in rare families with frontotemporal lobar degeneration (FTLD) but without bone involvement. We identified a p.Thr66Met heterozygous mutation in a new consanguineous Italian family. Two sibs had early onset autosomal recessive FTLD without severe bone disorders. Atypical signs were present in this family: early parietal and hippocampus involvement, parkinsonism, epilepsy, and corpus callosum thickness on brain magnetic resonance imaging. This study further demonstrates the implication of TREM2 mutations in FTLD phenotypes. It illustrates the variability of bone phenotype and underlines the frequency of atypical signs in TREM2 carriers. This and previous studies evidence that TREM2 mutation screening should be limited to autosomal recessive FTLD with atypical phenotypes characterized by: (1) a very young age at onset (20–50 years); (2) early parietal and hippocampal deficits; (3) the presence of seizures and parkinsonism; (4) suggestive extensive white matter lesions and corpus callosum thickness on brain magnetic resonance imaging. PMID:24910390

GNE missense mutation in recessive familial amyotrophic lateral sclerosis.

PubMed

Köroğlu, Çiğdem; Yılmaz, Rezzak; Sorgun, Mine Hayriye; Solakoğlu, Seyhun; Şener, Özden

2017-12-01

Amyotrophic lateral sclerosis (ALS) is a motor neuron disease eventually leading to death from respiratory failure. Recessive inheritance is very rare. Here, we describe the clinical findings in a consanguineous family with five men afflicted with recessive ALS and the identification of the homozygous mutation responsible for the disorder. The onset of the disease ranged from 12 to 35 years of age, with variable disease progressions. We performed clinical investigations including metabolic and paraneoplastic screening, cranial and cervical imaging, and electrophysiology. We mapped the disease gene to 9p21.1-p12 with a LOD score of 5.2 via linkage mapping using genotype data for single-nucleotide polymorphism markers and performed exome sequence analysis to identify the disease-causing gene variant. We also Sanger sequenced all coding sequences of SIGMAR1, a gene reported as responsible for juvenile ALS in a family. We did not find any mutation in SIGMAR1. Instead, we identified a novel homozygous missense mutation p.(His705Arg) in GNE which was predicted as damaging by online tools. GNE has been associated with inclusion body myopathy and is expressed in many tissues. We propose that the GNE mutation underlies the pathology in the family.

Woodhouse-Sakati syndrome in an Israeli-Arab family presenting with youth-onset diabetes mellitus and delayed puberty.

PubMed

Rachmiel, Marianna; Bistritzer, Tzvy; Hershkoviz, Eli; Khahil, Auni; Epstein, Orna; Parvari, Ruth

2011-01-01

Woodhouse-Sakati syndrome (WSS) is a rare autosomal-recessive disorder characterized by a combination of hypogonadism, alopecia, diabetes mellitus (DM), mental retardation and extrapyramidal signs, not described previously in Israel. Our aim was to study the clinical and genetic characteristics of the extended family of a 16-year-old female who presented with new-onset DM and had delayed puberty on physical examination. The primary physician's medical charts of 9 members of the proband's consanguineous Israeli-Arab family were reviewed. Hormonal, metabolic and antibody profile, imaging studies and molecular analysis were performed in 4 phenotypically compatible members, including the proband. Four subjects, 2 females and 2 males, had DM, absent pubertal development and similar appearance. None had extrapyramidal signs. The patients were homozygous for a one-base deletion mutation (c.436delC) in the C2orf37 gene. We describe the first Israeli-Arab family with phenotype and genotype of WSS, imitating autoimmune DM with gonadal failure. Copyright © 2011 S. Karger AG, Basel.

Parental consanguineous marriages and clinical response to chemotherapy in locally advanced breast cancer patients.

PubMed

Saadat, Mostafa; Khalili, Maryam; Omidvari, Shahpour; Ansari-Lari, Maryam

2011-03-28

The main aim of the present study was investigating the association between parental consanguinity and clinical response to chemotherapy in females affected with locally advanced breast cancer. A consecutive series of 92 patients were prospectively included in this study. Clinical assessment of treatment was accomplished by comparing initial tumor size with preoperative tumor size using revised RECIST guideline (version 1.1). Clinical response defined as complete response, partial response and no response. The Kaplan-Meier survival analysis were used to evaluate the association of parental marriages (first cousin vs unrelated marriages) and clinical response to chemotherapy (complete and partial response vs no response). Number of courses of chemotherapy was considered as time, in the analysis. Kaplan-Meier analysis revealed that offspring of unrelated marriages had poorer response to chemotherapy (log rank statistic=5.10, df=1, P=0.023). Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Domestic violence in consanguineous marriages - findings from Pakistan Demographic and Health Survey 2012-13.

PubMed

Shaikh, Masood Ali

2016-10-01

Domestic violence is a pandemic and estimated to affect one in three women globally, in their lifetime. Marriages within blood relations in Pakistan are common. In this study a secondary analysis of Pakistan Demographic and Health Survey 2012-13 was done to study the prevalence and profile of domestic violence in the context of consanguineous marriages in Pakistan. Almost 65% of women had some kind of blood relationship with their husbands. Women having a blood relationship with husbands were more likely to report having ever been subjected to marital control behaviours, emotional and physical violence by their husbands, compared to ones without such relationship. However, these associations fail to reach statistical significance; underscoring the ubiquitous nature of marital control and violence. More effective public health education campaigns for just and equal treatment of wives by their husbands to speedily curb the scourge of domestic violence in the country are needed.

Colorectal Cancer Mortality in Relation to Glucose - 6 - Phosphate Dehydrogenase Deficiency and Consanguinity in Sardinia: A Spatial Correlation Analysis

PubMed

Pes, Giovanni Mario; Bassotti, Gabrio; Dore, Maria Pina

2017-09-27

Background: Colorectal cancer (CRC) is one of the most diffuse malignancy in the world. In Southern Europe, the incidence and prevalence are lower than in most Western countries, although some hot spots of increased risk are emerging. In Sardinia, the cancer rate has risen steeply in the last years. Among risk factors for CRC, genomic homozygosity has been postulated. Glucose-6-phosphate dehydrogenase (G6PD) deficiency has been hypothesized to decrease CRC risk. In Sardinians, this disorder has a frequency of 12-24% due to selection by past malaria. In this study the relationship between mortality for CRC, homozygosity and G6PD deficiency was analysed using spatial analysis. Methods: The spatial association between CRC mortality and G6PD deficiency and homozygosity was assessed in the 377 municipalities of the island using ordinary least squares regression and geographically weighted regression. Results: A consanguinity index, available across all municipalities, was used as a proxy for homozygosity. A significant inverse correlation was found between CRC mortality and G6PD deficiency (ρ = ‒0.216; p = 0.002) whereas no association was found for consanguinity (ρ = ‒0.077; p = 0.498). The geographical map of CRC mortality showed a significant clustering in mountain areas compared to the population living in lowlands, whereas hot spot areas of G6PD deficiency were observed on the south-western side of Sardinia. Conclusions: These results indicate that G6PD deficiency might contribute to reduce colon carcinogenesis, and is in line with in vitro and in vivo studies. Creative Commons Attribution License

Linking Roles of Education Assistants in the Missouri Small Farm Family Program at the University Resource Subsystem Client Social System Interface.

ERIC Educational Resources Information Center

Lionberger, Herbert F.; Wong, Tso Sang

Growing concern that the Cooperative Extension Service was failing to adequately reach small farmers with education materials through regular extension channels led to the implementation of Missouri's Small Farm Family Program. In this program, education assistants, many of whom are small farmers themselves, link the educational resources of the…

Unusual association of turner syndrome and hypopituitarism in a Tunisian family.

PubMed

Bougacha-Elleuch, N; Elleuch, M; Charfi, N; Mnif, F; Belghith, N; Abdelhedi, F; Kammoun, H; Hachicha, M; Mnif, M; Abid, M

2016-01-01

Familial occurrence of either Turner syndrome or hypopituitarism is very rare. Particularly, their association is an uncommon finding. In this context, we describe for the first time 4 sisters with Turner syndrome, hypopituitarism was reported in three among them. Our cohort consists of four Tunisian adult sisters belonging to a consanguineous family. Biochemical analysis, resonance magnetic imaging and cytogenetic analyses were performed. Turner syndrome was diagnosed at the ages of 14, 17, 31 and 43 years in cases 1, 2, 3 and 4 respectively. They suffered from short stature, dysmorphic syndrome and/or delayed puberty. Interestingly, 3 among them showed also hypopituitarism, hypogonadotrophic hypogonadism and central hypothyroidism. Somatotropic insufficiency was proven in one case. Pituitary MRI has shown an empty sella turcica with hypoplastic pituitary gland in three cases. Their karyotypes were compatible with 45X in one case, 45X/46XX in the second and 45X/46XX/47XXY with x label in two cases. Hence, the presence of these familial cases of TS must evoke new etiopathogenetic arguments. Coincidence of hypopituitarism in this family, might suggest common genetic background for the two diseases. This particular family would be a precious tool for an extensive molecular analysis. More attention should be given to other family's members mainly in the presence of delayed puberty and sterility in other members. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Homozygosity mapping in autosomal recessive retinitis pigmentosa families detects novel mutations

PubMed Central

Marzouka, Nour al Dain; Hebrard, Maxime; Manes, Gaël; Sénéchal, Audrey; Meunier, Isabelle; Hamel, Christian P.

2013-01-01

Purpose Autosomal recessive retinitis pigmentosa (arRP) is a genetically heterogeneous disease resulting in progressive loss of photoreceptors that leads to blindness. To date, 36 genes are known to cause arRP, rendering the molecular diagnosis a challenge. The aim of this study was to use homozygosity mapping to identify the causative mutation in a series of inbred families with arRP. Methods arRP patients underwent standard ophthalmic examination, Goldman perimetry, fundus examination, retinal OCT, autofluorescence measurement, and full-field electroretinogram. Fifteen consanguineous families with arRP excluded for USH2A and EYS were genotyped on 250 K SNP arrays. Homozygous regions were listed, and known genes within these regions were PCR sequenced. Familial segregation and mutation analyzes were performed. Results We found ten mutations, seven of which were novel mutations in eight known genes, including RP1, IMPG2, NR2E3, PDE6A, PDE6B, RLBP1, CNGB1, and C2ORF71, in ten out of 15 families. The patients carrying RP1, C2ORF71, and IMPG2 mutations presented with severe RP, while those with PDE6A, PDE6B, and CNGB1 mutations were less severely affected. The five families without mutations in known genes could be a source of identification of novel genes. Conclusions Homozygosity mapping combined with systematic screening of known genes results in a positive molecular diagnosis in 66.7% of families. PMID:24339724

How a Small Family Run Business Adopted Critical Reflection Action Learning Using Hand Drawn Images to Initiate Organisational Change

ERIC Educational Resources Information Center

Shepherd, Gary

2016-01-01

In this account of practice I would like to share my experiences of facilitating a Critical Reflection Action Learning (CRAL) set with a small family run business, struggling to make change and expand their services due to the problems they encountered in separating their business lives from their family lives. The account I present here is based…

Three clinical experiences with SNP array results consistent with parental incest: a narrative with lessons learned.

PubMed

Helm, Benjamin M; Langley, Katherine; Spangler, Brooke; Vergano, Samantha

2014-08-01

Single nucleotide polymorphism microarrays have the ability to reveal parental consanguinity which may or may not be known to healthcare providers. Consanguinity can have significant implications for the health of patients and for individual and family psychosocial well-being. These results often present ethical and legal dilemmas that can have important ramifications. Unexpected consanguinity can be confounding to healthcare professionals who may be unprepared to handle these results or to communicate them to families or other appropriate representatives. There are few published accounts of experiences with consanguinity and SNP arrays. In this paper we discuss three cases where molecular evidence of parental incest was identified by SNP microarray. We hope to further highlight consanguinity as a potential incidental finding, how the cases were handled by the clinical team, and what resources were found to be most helpful. This paper aims to contribute further to professional discourse on incidental findings with genomic technology and how they were addressed clinically. These experiences may provide some guidance on how others can prepare for these findings and help improve practice. As genetic and genomic testing is utilized more by non-genetics providers, we also hope to inform about the importance of engaging with geneticists and genetic counselors when addressing these findings.

Cortical atrophy and hypofibrinogenemia due to FGG and TBCD mutations in a single family: a case report.

PubMed

Stephen, Joshi; Nampoothiri, Sheela; Vinayan, K P; Yesodharan, Dhanya; Remesh, Preetha; Gahl, William A; Malicdan, May Christine V

2018-05-16

Blended phenotypes or co-occurrence of independent phenotypically distinct conditions are extremely rare and are due to coincidence of multiple pathogenic mutations, especially due to consanguinity. Hereditary fibrinogen deficiencies result from mutations in the genes FGA, FGB, and FGG, encoding the three different polypeptide chains that comprise fibrinogen. Neurodevelopmental abnormalities have not been associated with fibrinogen deficiencies. In this study, we report an unusual patient with a combination of two independently inherited genetic conditions; fibrinogen deficiency and early onset cortical atrophy. The study describes a male child from consanguineous family presented with hypofibrinogenemia, diffuse cortical atrophy, microcephaly, hypertonia and axonal motor neuropathy. Through a combination of homozygosity mapping and exome sequencing, we identified bi-allelic pathogenic mutations in two genes: a homozygous novel truncating mutation in FGG (c.554del; p.Lys185Argfs*14) and a homozygous missense mutation in TBCD (c.1423G > A;p.Ala475Thr). Loss of function mutations in FGG have been associated with fibrinogen deficiency, while the c.1423G > A mutation in TBCD causes a novel syndrome of neurodegeneration and early onset encephalopathy. Our study highlights the importance of homozygosity mapping and exome sequencing in molecular prenatal diagnosis, especially when multiple gene mutations are responsible for the phenotype.

Cancerous leptomeningitis and familial congenital hypopituitarism.

PubMed

Vujovic, S; Vujosevic, S; Kavaric, S; Sopta, J; Ivovic, M; Saveanu, A; Brue, T; Korbonits, M; Popovic, V

2016-05-01

People are at higher risk of cancer as they get older or have a strong family history of cancer. The potential influence of environmental and behavioral factors remains poorly understood. Earlier population and case control studies reported that upper quartile of circulating IGF-I is associated with a higher risk of developing cancer suggesting possible involvement of the growth hormone (GH)/IGF system in initiation or progression of cancer. Since GH therapy increases IGF-1 levels, there have been concerns that GH therapy in hypopituitarism might increase the risk of cancer. We report a 42-year-old female patient who presented with subacute onset of symptoms of meningitis and with the absence of fever which resulted in death 70 days after the onset of symptoms. The patient together with her younger brother was diagnosed at the age of 5 years with familial congenital hypopituitarism, due to homozygous mutation c.150delA in PROP1 gene. Due to evolving hypopituitarism, she was replaced with thyroxine (from age 5), hydrocortisone (from age 13), GH (from age 13 until 17), and sex steroids in adolescence and adulthood. Her consanguineous family has a prominent history of malignant diseases. Six close relatives had malignant disease including her late maternal aunt with breast cancer. BRCA 1 and BRCA 2 mutational analysis in the patient's mother was negative. Histology after autopsy disclosed advanced ovarian cancer with multiple metastases to the brain, leptomeninges, lungs, heart, and adrenals. Low circulating IGF-1 did not seem to protect this patient from cancer initiation and progression in the context of strong family history of malignancies.

Ectrodactyly with aplasia of long bones (OMIM; 119100) in a large inbred Arab family with an apparent autosomal dominant inheritance and reduced penetrance: clinical and genetic analysis.

PubMed

Naveed, Mohammed; Al-Ali, Mahmoud T; Murthy, Sabita K; Al-Hajali, Sarah; Al-Khaja, Najib; Deutsch, Samuel; Bottani, Armand; Antonarakis, Stylianos E; Nath, Swapan K; Radhakrishna, Uppala

2006-07-01

Ectrodactyly with aplasia of long bones syndrome is one of the most recognizable defects involving the extremities. We have studied a very large eight-generation consanguineous Arab family from the United Arab Emirates (UAE) with multiple severe limb anomalies resembling this condition (OMIM; 119100), for which the affected gene is unknown. The pedigree consists of 145 individuals including 23 affected (14 males/9 females) with limb anomalies. Of these, 18 had tibial aplasia (TA) usually on the right side. The expression of the phenotype was variable and ranged from bilateral to unilateral TA with ectrodactyly and other defects of the extremities. The mode of inheritance appears to be autosomal dominant with reduced penetrance. There were 10 consanguineous marriages observed in this pedigree. This could suggest possible pseudodominance due to high frequency of the mutant allele. Candidate loci for the described syndrome include GLI3 (OMIM: 165240) on 7p13, sonic hedgehog; (OMIM: 600725) on 7q36, Langer-Giedion syndrome (OMIM: 150230) on 8q24.1 and split-hand/foot malformation 3 (OMIM: 600095) on 10q24. In addition, bilateral tibial hemimelia and unilateral absence of the ulna was previously observed to co-segregate with deletion of 8q24.1. Two-point linkage and haplotype analyses did not show the involvement of the above regions in this family. (c) 2006 Wiley-Liss, Inc.

Small leucine rich proteoglycan family regulates multiple signalling pathways in neural development and maintenance.

PubMed

Dellett, Margaret; Hu, Wanzhou; Papadaki, Vasiliki; Ohnuma, Shin-ichi

2012-04-01

The small leucine-rich repeat proteoglycan (SLRPs) family of proteins currently consists of five classes, based on their structural composition and chromosomal location. As biologically active components of the extracellular matrix (ECM), SLRPs were known to bind to various collagens, having a role in regulating fibril assembly, organization and degradation. More recently, as a function of their diverse proteins cores and glycosaminoglycan side chains, SLRPs have been shown to be able to bind various cell surface receptors, growth factors, cytokines and other ECM components resulting in the ability to influence various cellular functions. Their involvement in several signaling pathways such as Wnt, transforming growth factor-β and epidermal growth factor receptor also highlights their role as matricellular proteins. SLRP family members are expressed during neural development and in adult neural tissues, including ocular tissues. This review focuses on describing SLRP family members involvement in neural development with a brief summary of their role in non-neural ocular tissues and in response to neural injury. © 2012 The Authors Development, Growth & Differentiation © 2012 Japanese Society of Developmental Biologists.

Enhancing health literacy through co-design: development of culturally appropriate materials on genetic risk and customary consanguineous marriage.

PubMed

Ali, Parveen Azam; Salway, Sarah; Such, Elizabeth; Dearden, Andrew; Willox, Matt

2018-04-12

AimTo develop a simple health literacy intervention aimed at supporting informed reproductive choice among members of UK communities practising customary consanguineous marriage. The contribution of 'health literacy' to reducing health inequalities and improving primary health-care efficiency is increasingly recognised. Enhancing genetic literacy has received particular attention recently. Consanguineous marriage is customarily practised among some UK minority ethnic communities and carries some increased risk of recessive genetic disorders among offspring compared with unions among unrelated partners. The need to enhance genetic literacy on this issue has been highlighted, but no national response has ensued. Instead, a range of undocumented local responses are emerging. Important knowledge gaps remain regarding how the development and implementation of culturally appropriate, effective and sustainable responses can be achieved. Our co-design approach involved active participation by local people. Initial insight generation employed six focus group discussions and 14 individual interviews to describe current understandings and information needs. A total of 11 personas (heuristic narrative portraits of community 'segments') resulted; four participatory workshops provided further understanding of: preferred information channels; feasible information conveyance; and responses to existing materials. Prototype information resources were then developed and feedback gathered via two workshops. Following further refinement, final feedback from health-care professionals and community members ensured accuracy and appropriateness.FindingsThe project demonstrated the utility of co-design for addressing an issue often considered complex and sensitive. With careful planning and orchestration, active participation by diverse community members was achieved. Key learning included: the importance of establishing trusting and respectful relationships; responding to diversity within

The Spectrum of Familial Hypercholesterolemia (FH) in Saudi Arabia: Prime Time for Patient FH Registry

PubMed Central

Alallaf, Faisal; H.Nazar, Fatima Amanullah; Alnefaie, Majed; Almaymuni, Adel; Rashidi, Omran Mohammed; Alhabib, Khalid; Alnouri, Fahad; Alama, Mohamed-Nabil; Athar, Mohammad; Awan, Zuhier

2017-01-01

Background: Familial hypercholesterolemia (FH) is a life-threatening inherited condition. Untreated patients have the risk to develop raised plasma levels of cholesterol, atherosclerosis and cardiovascular disease (CVD). If diagnosed and treated early in life, the pathological consequences due to atherosclerosis could be avoided and patients with FH can have an anticipated normal life. Mounting evidence suggests that FH is underdiagnosed and undertreated in all populations. The underlying molecular basis of FH is the presence of mutations in one or more genes in the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB) or proprotein convertase subtilisin/kexin 9 (PCSK9). However, their prevalence is largely unknown in Saudi Arabia but given the high rates of consanguinity, the prevalence appears to be higher. Furthermore, the high prevalence of obesity and diabetes mellitus in Saudi Arabia increases the vascular disease burden in FH cases by adding additional CVD risk factors. Objective: This article explores the spectrum of FH-causing mutations in the highly consanguineous Saudi community, the need for establishing the Saudi FH registry, the challenges in creating gene databases, and cascade screening. Conclusion: The establishment of FH registry and genetic testing should raise awareness not only among healthcare professionals, but the general population as well. It also helps to provide the best treatment regimen in a cost effective manner to this under-recognised population of FH patients. PMID:28868092

Homozygosity mapping reveals new nonsense mutation in the FAM161A gene causing autosomal recessive retinitis pigmentosa in a Palestinian family.

PubMed

Zobor, Ditta; Balousha, Ghassan; Baumann, Britta; Wissinger, Bernd

2014-01-01

Retinitis pigmentosa (RP) is a heterogenous group of inherited retinal degenerations caused by mutations in at least 45 genes. Recently, the FAM161A gene was identified as the causative gene for RP28, an autosomal recessive form of RP. We performed a clinical and molecular genetic study of a consanguineous Palestinian family with two three siblings affected with retinitis pigmentosa. DNA samples were collected from the index patient, his father, his affected sister, and two non-affected brothers. DNA sample from the index was subjected to high resolution genome-wide SNP array. Assuming identity-by-descent in this consanguineous family we applied homozygosity mapping to identify disease causing genes. The index patient reported night blindness since the age of 20 years, followed by moderate disease progression with decrease of peripheral vision, the development of photophobia and later on reduced central vision. At the age of 40 his visual acuity was counting fingers (CF) for both eyes, color discrimination was not possible and his visual fields were severely constricted. Funduscopic examination revealed a typical appearance of advanced RP with optic disc pallor, narrowed retinal vessels, bone-spicule like pigmentary changes in the mid-periphery and atrophic changes in the macula. His younger affected brother (37 years) was reported with overall milder symptoms, while the youngest sister (21 years) reported problems only with night vision. Applying high-density SNP arrays we identified several homozygous genomic regions one of which included the recently identified FAM161A gene mutated in RP28-linked autosomal recessive RP. Sequencing analysis revealed the presence of a novel homozygous nonsense mutation, c.1003C>T/p.R335X in the index patient and the affected sister. We identified an RP28-linked RP family in the Palestinian population caused by a novel nonsense mutation in FAM161A. RP in this family shows a typical disease onset with moderate to rapid progression

Homozygosity mapping reveals new nonsense mutation in the FAM161A gene causing autosomal recessive retinitis pigmentosa in a Palestinian family

PubMed Central

Zobor, Ditta; Balousha, Ghassan; Baumann, Britta

2014-01-01

Purpose: Retinitis pigmentosa (RP) is a heterogenous group of inherited retinal degenerations caused by mutations in at least 45 genes. Recently, the FAM161A gene was identified as the causative gene for RP28, an autosomal recessive form of RP. Methods: We performed a clinical and molecular genetic study of a consanguineous Palestinian family with two three siblings affected with retinitis pigmentosa. DNA samples were collected from the index patient, his father, his affected sister, and two non-affected brothers. DNA sample from the index was subjected to high resolution genome-wide SNP array. Assuming identity-by-descent in this consanguineous family we applied homozygosity mapping to identify disease causing genes. Results: The index patient reported night blindness since the age of 20 years, followed by moderate disease progression with decrease of peripheral vision, the development of photophobia and later on reduced central vision. At the age of 40 his visual acuity was counting fingers (CF) for both eyes, color discrimination was not possible and his visual fields were severely constricted. Funduscopic examination revealed a typical appearance of advanced RP with optic disc pallor, narrowed retinal vessels, bone-spicule like pigmentary changes in the mid-periphery and atrophic changes in the macula. His younger affected brother (37 years) was reported with overall milder symptoms, while the youngest sister (21 years) reported problems only with night vision. Applying high-density SNP arrays we identified several homozygous genomic regions one of which included the recently identified FAM161A gene mutated in RP28-linked autosomal recessive RP. Sequencing analysis revealed the presence of a novel homozygous nonsense mutation, c.1003C>T/p.R335X in the index patient and the affected sister. Conclusion: We identified an RP28-linked RP family in the Palestinian population caused by a novel nonsense mutation in FAM161A. RP in this family shows a typical disease

The potential impact of family history of metabolic syndrome and risk of type 2 diabetes mellitus: In a highly endogamous population.

PubMed

Bener, Abdulbari; Darwish, Sarah; Al-Hamaq, Abdulla O A; Yousafzai, Mohammad T; Nasralla, Eman A

2014-03-01

This study aims to determine the potential impact of positive family history of Metabolic Syndrome (MetS) among two generations, on developing Type 2 Diabetes Mellitus (T2DM) and the potential relation of consanguineous marriage among patients with MetS to the risk of developing T2DM among a sample of Qataris. A cross-sectional study. Primary healthcare (PHC) centers. The survey and measurement were conducted from April 2011 to December 2012 among Qatari nationals above 20 years of age. Of the 2,182 subjects, who were approached to participate in the study, 1,552 (71%) gave their consent. Face-to-face interviews were conducted using a structured questionnaire followed by anthropometric measurements and laboratory tests. Metabolic syndrome was defined using the National Cholesterol Education Program-Third Adult Treatment Panel (ATP III) as well as International Diabetes Federation (IDF). Overall, the prevalence of MetS was 26.2% according to ATP III and 36.9% according to IDF (P < 0.0001). The mean age of MetS patients with T2DM was significantly higher than those without T2DM (Mean 48 ± 9.9 vs. 42.5 ± 9.2; P < 0.001). The proportion of females was higher among MetS patients with T2DM as compared to those without T2DM (61% vs. 51%; P = 0.053). In addition, there were significant differences between MetS patients with and without DM in terms of co-morbidities of hypertension, coronary heart disease, and high cholesterol. The proportion of MetS patients with positive family history for MetS was significantly higher in MetS patients with T2DM as compared to those without T2DM (46.7% vs. 33.8%; P = 0.009). The proportion of positive family history of MetS among fathers (35% vs. 21.9%; P = 0.005), mothers (30.5% vs. 18.8%; P = 0.008), maternal aunt (18.3% vs. 11.2%; P = 0.055), and maternal grand father (19.5% vs. 10%; P = 0.010) were significantly higher in MetS patients with T2DM as compared to the counterpart. The proportion of consanguineous marriages was almost

Poikiloderma with neutropenia, Clericuzio type, in a family from Morocco.

PubMed

Mostefai, Rahima; Morice-Picard, Fanny; Boralevi, Franck; Sautarel, Michel; Lacombe, Didier; Stasia, Marie José; McGrath, John; Taïeb, Alain

2008-11-01

Three siblings from Morocco consanguineous family presented with cutaneous poikiloderma following postnatal ichthyosiform lesions, associated with papillomatous lesions, palmoplantar keratoderma, pachyonychia of toenails, fragile carious teeth, and lachrymal duct obstruction. Photosensitivity and blistering improved with age. Atrophic scars were prominent on the limbs. Neutropenia developed in the first year secondary to dysmyelopoiesis affecting the granulocyte lineage, associated with a polyclonal hypergammaglobulinemia. Several broncho-pulmonary infectious episodes complicated the evolution, and cystic fibrosis was first considered on the basis of repeated abnormal sweat chloride tests but not confirmed by molecular analyses. This autosomal recessive disorder matches that described originally as poikiloderma with neutropenia-Clericuzio type in Navajo Indians (OMIM 604173). It is discussed within the group of the major hereditary poikiloderma disorders, that is, Rothmund-Thomson syndrome, dyskeratosis congenita, and Kindler syndrome. Copyright 2008 Wiley-Liss, Inc.

Interconversion of two GDP-bound conformations and their selection in an Arf-family small G protein.

PubMed

Okamura, Hideyasu; Nishikiori, Masaki; Xiang, Hongyu; Ishikawa, Masayuki; Katoh, Etsuko

2011-07-13

ADP-ribosylation factor (Arf) and other Arf-family small G proteins participate in many cellular functions via their characteristic GTP/GDP conformational cycles, during which a nucleotide(∗)Mg(2+)-binding site communicates with a remote N-terminal helix. However, the conformational interplay between the nucleotides, the helix, the protein core, and Mg(2+) has not been fully delineated. Herein, we report a study of the dynamics of an Arf-family protein, Arl8, under various conditions by means of NMR relaxation spectroscopy. The data indicated that, when GDP is bound, the protein core, which does not include the N-terminal helix, reversibly transition between an Arf-family GDP form and another conformation that resembles the Arf-family GTP form. Additionally, we found that the N-terminal helix and Mg(2+), respectively, stabilize the aforementioned former and latter conformations in a population-shift manner. Given the dynamics of the conformational changes, we can describe the Arl8 GTP/GDP cycle in terms of an energy diagram. Copyright © 2011 Elsevier Ltd. All rights reserved.

Waardenburg syndrome type I: Dental phenotypes and genetic analysis of an extended family.

PubMed

Sólia-Nasser, L; de Aquino, S-N; Paranaíba, L-M R; Gomes, A; Dos-Santos-Neto, P; Coletta, R-D; Cardoso, A-F; Frota, A-C; Martelli-Júnior, H

2016-05-01

The aim of this study was to describe the pattern of inheritance and the clinical features in a large family with Waardenburg syndrome type I (WS1), detailing the dental abnormalities and screening for PAX3 mutations. To characterize the pattern of inheritance and clinical features, 29 family members were evaluated by dermatologic, ophthalmologic, otorhinolaryngologic and orofacial examination. Molecular analysis of the PAX3 gene was performed. The pedigree of the family,including the last four generations, was constructed and revealed non-consanguineous marriages. Out of 29 descendants, 16 family members showed features of WS1, with 9 members showing two major criteria indicative of WS1. Five patients showed white forelock and iris hypopigmentation, and four showed dystopia canthorum and iris hypopigmentation. Two patients had hearing loss. Dental abnormalities were identified in three family members, including dental agenesis, conical teeth and taurodontism. Sequencing analysis failed to identify mutations in the PAX3 gene. These results confirm that WS1 was transmitted in this family in an autosomal dominant pattern with variable expressivity and high penetrance. The presence of dental manifestations, especially tooth agenesis and conical teeth which resulted in considerable aesthetic impact on affected individuals was a major clinical feature. This article reveals the presence of well-defined dental changes associated with WS1 and tries to establish a possible association between these two entities showing a new spectrum of WS1.

Clinical and molecular characterization of females affected by X-linked retinoschisis.

PubMed

Staffieri, Sandra E; Rose, Loreto; Chang, Andrew; De Roach, John N; McLaren, Terri L; Mackey, David A; Hewitt, Alex W; Lamey, Tina M

2015-01-01

X-linked retinoschisis (XLRS) is a leading cause of juvenile macular degeneration associated with mutations in the RS1 gene. XLRS has a variable expressivity in males and shows no clinical phenotype in carrier females. Clinical and molecular characterization of male and female individuals affected with XLRS in a consanguineous family. Consanguineous Eastern European-Australian family Four clinically affected and nine unaffected family members were genetically and clinically characterized. Deoxyribonucleic acid (DNA) analysis was conducted by the Australian Inherited Retinal Disease Register and DNA Bank. Clinical and molecular characterization of the causative mutation in a consanguineous family with XLRS. By direct sequencing of the RS1 gene, one pathogenic variant, NM_000330.3: c.304C > T, p. R102W, was identified in all clinically diagnosed individuals analysed. The two females were homozygous for the variant, and the males were hemizygous. Clinical and genetic characterization of affected homozygous females in XLRS affords the rare opportunity to explore the molecular mechanisms of XLRS and the manifestation of these mutations as disease in humans. © 2015 Royal Australian and New Zealand College of Ophthalmologists.

Genetic analysis of Chinese families reveals a novel truncation allele of the retinitis pigmentosa GTPase regulator gene

PubMed Central

Hu, Fang; Zeng, Xiang-Yun; Liu, Lin-Lin; Luo, Yao-Ling; Jiang, Yi-Ping; Wang, Hui; Xie, Jing; Hu, Cheng-Quan; Gan, Lin; Huang, Liang

2014-01-01

AIM To make comprehensive molecular diagnosis for retinitis pigmentosa (RP) patients in a consanguineous Han Chinese family using next generation sequencing based Capture-NGS screen technology. METHODS A five-generation Han Chinese family diagnosed as non-syndromic X-linked recessive RP (XLRP) was recruited, including four affected males, four obligate female carriers and eleven unaffected family members. Capture-NGS was performed using a custom designed capture panel covers 163 known retinal disease genes including 47 RP genes, followed by the validation of detected mutation using Sanger sequencing in all recruited family members. RESULTS Capture-NGS in one affected 47-year-old male reveals a novel mutation, c.2417_2418insG:p.E806fs, in exon ORF15 of RP GTPase regulator (RPGR) gene results in a frameshift change that results in a premature stop codon and a truncated protein product. The mutation was further validated in three of four affected males and two of four female carriers but not in the other unaffected family members. CONCLUSION We have identified a novel mutation, c.2417_2418insG:p.E806fs, in a Han Chinese family with XLRP. Our findings expand the mutation spectrum of RPGR and the phenotypic spectrum of XLRP in Han Chinese families, and confirms Capture-NGS could be an effective and economic approach for the comprehensive molecular diagnosis of RP. PMID:25349787

Variable hearing impairment in a DFNB2 family with a novel MYO7A missense mutation.

PubMed

Hildebrand, M S; Thorne, N P; Bromhead, C J; Kahrizi, K; Webster, J A; Fattahi, Z; Bataejad, M; Kimberling, W J; Stephan, D; Najmabadi, H; Bahlo, M; Smith, R J H

2010-06-01

Myosin VIIA mutations have been associated with non-syndromic hearing loss (DFNB2; DFNA11) and Usher syndrome type 1B (USH1B). We report clinical and genetic analyses of a consanguineous Iranian family segregating autosomal recessive non-syndromic hearing loss (ARNSHL). The hearing impairment was mapped to the DFNB2 locus using Affymetrix 50K GeneChips; direct sequencing of the MYO7A gene was completed. The Iranian family (L-1419) was shown to segregate a novel homozygous missense mutation (c.1184G>A) that results in a p.R395H amino acid substitution in the motor domain of the myosin VIIA protein. As one affected family member had significantly less severe hearing loss, we used a candidate approach to search for a genetic modifier. This novel MYO7A mutation is the first reported to cause DFNB2 in the Iranian population and this DFNB2 family is the first to be associated with a potential modifier. The absence of vestibular and retinal defects, and less severe low frequency hearing loss, is consistent with the phenotype of a recently reported Pakistani DFNB2 family. Thus, we conclude this family has non-syndromic hearing loss (DFNB2) rather than USH1B, providing further evidence that these two diseases represent discrete disorders.

Disease severity and treatment requirements in familial inflammatory bowel disease.

PubMed

Ballester, María Pilar; Martí, David; Tosca, Joan; Bosca-Watts, Marta Maia; Sanahuja, Ana; Navarro, Pablo; Pascual, Isabel; Antón, Rosario; Mora, Francisco; Mínguez, Miguel

2017-08-01

Several studies demonstrate an increased prevalence and concordance of inflammatory bowel disease among the relatives of patients. Other studies suggest that genetic influence is over-estimated. The aims of this study are to evaluate the phenotypic expression and the treatment requirements in familial inflammatory bowel disease, to study the relationship between number of relatives and degree of kinship with disease severity and to quantify the impact of family aggregation compared to other environmental factors. Observational analytical study of 1211 patients followed in our unit. We analyzed, according to the existence of familial association, number and degree of consanguinity, the phenotypic expression, complications, extraintestinal manifestations, treatment requirements, and mortality. A multivariable analysis considering smoking habits and non-steroidal-anti-inflammatory drugs was performed. 14.2% of patients had relatives affected. Median age at diagnosis tended to be lower in the familial group, 32 vs 29, p = 0.07. In familial ulcerative colitis, there was a higher proportion of extraintestinal manifestations: peripheral arthropathy (OR = 2.3, p = 0.015) and erythema nodosum (OR = 7.6, p = 0.001). In familial Crohn's disease, there were higher treatment requirements: immunomodulators (OR = 1.8, p = 0.029); biologics (OR = 1.9, p = 0.011); and surgery (OR = 1.7, p = 0.044). The abdominal abscess increased with the number of relatives affected: 5.1% (sporadic), 7.0% (one), and 14.3% (two or more), p=0.039. These associations were maintained in the multivariate analysis. Familial aggregation is considered a risk factor for more aggressive disease and higher treatment requirements, a tendency for earlier onset, more abdominal abscess, and extraintestinal manifestations, remaining a risk factor analyzing the influence of some environmental factors.

Phenotypic concordance in familial inflammatory bowel disease (IBD). Results of a nationwide IBD Spanish database.

PubMed

Cabré, Eduard; Mañosa, Míriam; García-Sánchez, Valle; Gutiérrez, Ana; Ricart, Elena; Esteve, Maria; Guardiola, Jordi; Aguas, Mariam; Merino, Olga; Ponferrada, Angel; Gisbert, Javier P; Garcia-Planella, Esther; Ceña, Gloria; Cabriada, José L; Montoro, Miguel; Domènech, Eugeni

2014-07-01

Disease outcome has been found to be poorer in familial inflammatory bowel disease (IBD) than in sporadic forms, but assessment of phenotypic concordance in familial IBD provided controversial results. We assessed the concordance for disease type and phenotypic features in IBD families. Patients with familial IBD were identified from the IBD Spanish database ENEIDA. Families in whom at least two members were in the database were selected for concordance analysis (κ index). Concordance for type of IBD [Crohn's disease (CD) vs. ulcerative colitis (UC)], as well as for disease extent, localization and behaviour, perianal disease, extraintestinal manifestations, and indicators of severe disease (i.e., need for immunosuppressors, biological agents, and surgery) for those pairs concordant for IBD type, were analyzed. 798 out of 11,905 IBD patients (7%) in ENEIDA had familial history of IBD. Complete data of 107 families (231 patients and 144 consanguineous pairs) were available for concordance analyses. The youngest members of the pairs were diagnosed with IBD at a significantly younger age (p<0.001) than the oldest ones. Seventy-six percent of pairs matched up for the IBD type (κ=0.58; 95%CI: 0.42-0.73, moderate concordance). There was no relevant concordance for any of the phenotypic items assessed in both diseases. Familial IBD is associated with diagnostic anticipation in younger individuals. Familial history does not allow predicting any phenotypic feature other than IBD type. Copyright © 2013 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

LGMD2D syndrome: the importance of clinical and molecular genetics in patient and family management. Case Report.

PubMed

Al-Harbi, Khalid M; Abdallah, Atiyeh M

2016-09-01

We report the case of a seven-year-old female from a consanguineous Saudi family with autosomal recessive limb girdle muscular dystrophy type 2D (LGMD2D) most likely caused by a rare SGCA mutation. Histopathological and molecular investigations resulted in the discovery of a homozygous mutation (c.226 C>T (p.L76 F)) in exon 3 of SGCA in the patient. The parents and one sibling were heterozygous carriers, but the mutation was not otherwise detected in 80 ethnic controls from the same geographic area. In silico analysis revealed that the mutation resulted in a functional leucine to phenylalanine alteration that was deleterious to the protein structure. This is only the second reported case of the p.L76F mutation in LGMD, and highlights that molecular genetics analysis is essential to deliver the most appropriate management to the patient and offer the family genetic counseling.

[Serological Characteristics and Family Survey of 3 Cases of H-deficient Blood Group].

PubMed

Geng, Wei; Gao, Huan-Huan; Zhang, Lin-Wei

2016-06-01

To investigate the serological characteristics and the genetic status of the family of H-deficient blood group in Jining area of Shandong province in China. ABO, H, and Lewis blood groups in 3 probands were screened out by the serological method, and saliva testing was performed on all the individuals. The presence of weak A or B on the RBC was confirmed by using the adsorption-elution procedure. Three cases of H-deficient blood group were identified to be para-Bombay blood group (secretor), out of 3 cases, 2 cases were Bh, 1 case was Ah, and anti-H or anti-HI antibody was detected in their serum. Three cases of H-deficerent blood group are para-Bombay phenotype, among them one proband's parents have been confirmed to be consanguineous relationship.

Investigation of current university research concerning energy conversion and conservation in small single-family dwellings

NASA Technical Reports Server (NTRS)

Grossman, G. R.; Roberts, A. S., Jr.

1975-01-01

An investigation was made of university research concerning energy conversion and conservation techniques which may be applied in small single-family residences. Information was accumulated through published papers, progress reports, telephone conversations, and personal interviews. A synopsis of each pertinent investigation is given. Finally, a discussion of the synopses is presented and recommendations are made concerning the applicability of concepts for the design and construction of NASA-Langley Research Center's proposed Technology Utilization House in Hampton, Virginia.

Waardenburg syndrome type I: Dental phenotypes and genetic analysis of an extended family

PubMed Central

de Aquino, Sibele-Nascimento; Paranaíba, Lívia-Maris-R.; Gomes, Andreia; dos-Santos-Neto, Pedro; Coletta, Ricardo-D.; Cardoso, Aline-Francoise; Frota, Ana-Cláudia; Martelli-Júnior, Hercílio

2016-01-01

Background The aim of this study was to describe the pattern of inheritance and the clinical features in a large family with Waardenburg syndrome type I (WS1), detailing the dental abnormalities and screening for PAX3 mutations. Material and Methods To characterize the pattern of inheritance and clinical features, 29 family members were evaluated by dermatologic, ophthalmologic, otorhinolaryngologic and orofacial examination. Molecular analysis of the PAX3 gene was performed. Results The pedigree of the family,including the last four generations, was constructed and revealed non-consanguineous marriages. Out of 29 descendants, 16 family members showed features of WS1, with 9 members showing two major criteria indicative of WS1. Five patients showed white forelock and iris hypopigmentation, and four showed dystopia canthorum and iris hypopigmentation. Two patients had hearing loss. Dental abnormalities were identified in three family members, including dental agenesis, conical teeth and taurodontism. Sequencing analysis failed to identify mutations in the PAX3 gene. Conclusions These results confirm that WS1 was transmitted in this family in an autosomal dominant pattern with variable expressivity and high penetrance. The presence of dental manifestations, especially tooth agenesis and conical teeth which resulted in considerable aesthetic impact on affected individuals was a major clinical feature. Clinical relevance: This article reveals the presence of well-defined dental changes associated with WS1 and tries to establish a possible association between these two entities showing a new spectrum of WS1. Key words:Waardenburg syndrome, hearing loss, oral manifestations, mutation. PMID:27031059

Genetic homogeneity in Sjoegren-Larsson syndrome: Linkage to chromosome 17p in families of different non-Swedish ethnic origins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rogers, G.R.; Lee, M.; Compton, J.G.

1995-11-01

Sjoegren-Larsson syndrome (SLS) is a rare, autosomal recessive disorder that is characterized by congenital ichthyosis, mental retardation, and spastic diplegia or tetraplegia. Three United States families, three Egyptian families, and one Israeli Arab family were investigated for linkage of the SLS gene to a region of chromosome 17. Pairwise and multipoint linkage analysis with nine markers mapped the SLS gene to the same region of the genome as that reported in Swedish SLS pedigrees. Examination of recombinants by haplotype analysis showed that the gene lies in the region containing the markers D17S953, D17S805, D17S689, and D17S842. D17S805 is pericentromeric onmore » 17p. Patients in two consanguineous Egyptian families were homozygous at the nine marker loci tested, and another patient from a third family was homozygous for eight of the nine, suggesting that within each of these families the region of chromosome 17 carrying the SLS gene is identical by descent. Linkage of the SLS gene to chromosome 17p in families of Arabic, mixed European, Native American, and Swedish descent provides evidence for a single SLS locus and should prove useful for diagnosis and carrier detection in worldwide cases. 25 refs., 4 figs., 1 tab.« less

Prognostic impact of EGFR mutation in non-small-cell lung cancer patients with family history of lung cancer.

PubMed

Kim, Jung Soo; Cho, Min Seong; Nam, Jong Hyeon; Kim, Hyun-Jung; Choi, Kyeng-Won; Ryu, Jeong-Seon

2017-01-01

A family history can be a valuable tool in the era of precision medicine. Although a few studies have described an association of family history of lung cancer with EGFR activating mutation, their impact on survival of lung cancer patients is unclear. The study included consecutive 829 non-small-cell lung cancer patients who received analysis of EGFR mutation in a prospective lung cancer cohort. Family history of lung cancer was obtained by face-to-face interviews at the time of diagnosis. An association of EGFR activating mutation with a family history of lung cancer in first-degree relatives was evaluated with multivariate logistic regression analysis, and its association with survival was estimated with Cox's proportional hazards model. Seventy five (9.0%) patients had family history of lung cancer. The EGFR mutation was commonly observed in patients with positive family history compared to those with no family history (46.7% v 31.3%, χ2 p = 0.007). The family history was significantly associated with the EGFR mutation (aOR and 95% CI: 2.01 and 1.18-3.60, p = 0.011). Patients with the positive family history survived longer compared to those without (MST, 17.9 v 13.0 months, log-rank p = 0.037). The presence of the EGFR mutation was associated with better survival in patients without the family history (aHR and 95% CI: 0.72 and 0.57-0.90, p = 0.005). However, this prognostic impact was not observed in patients with the positive family history (aHR and 95% CI: 1.01 and 0.50-2.36, p = 0.832). In comparison to patients without the family history, EGFR activating mutation was common, and it did not affect prognosis in patients with positive family history.

The effects of small-scale, homelike facilities for older people with dementia on residents, family caregivers and staff: design of a longitudinal, quasi-experimental study.

PubMed

Verbeek, Hilde; van Rossum, Erik; Zwakhalen, Sandra M G; Ambergen, Ton; Kempen, Gertrudis I J M; Hamers, Jan P H

2009-01-20

Small-scale and homelike facilities for older people with dementia are rising in current dementia care. In these facilities, a small number of residents live together and form a household with staff. Normal, daily life and social participation are emphasized. It is expected that these facilities improve residents' quality of life. Moreover, it may have a positive influence on staff's job satisfaction and families involvement and satisfaction with care. However, effects of these small-scale and homelike facilities have hardly been investigated. Since the number of people with dementia increases, and institutional long-term care is more and more organized in small-scale and homelike facilities, more research into effects is necessary. This paper presents the design of a study investigating effects of small-scale living facilities in the Netherlands on residents, family caregivers and nursing staff. A longitudinal, quasi-experimental study is carried out, in which 2 dementia care settings are compared: small-scale living facilities and regular psychogeriatric wards in traditional nursing homes. Data is collected from residents, their family caregivers and nursing staff at baseline and after 6 and 12 months of follow-up. Approximately 2 weeks prior to baseline measurement, residents are screened on cognition and activities of daily living (ADL). Based on this screening profile, residents in psychogeriatric wards are matched to residents living in small-scale living facilities. The primary outcome measure for residents is quality of life. In addition, neuropsychiatric symptoms, depressive symptoms and social engagement are assessed. Involvement with care, perceived burden and satisfaction with care provision are primary outcome variables for family caregivers. The primary outcomes for nursing staff are job satisfaction and motivation. Furthermore, job characteristics social support, autonomy and workload are measured. A process evaluation is performed to investigate to

Novel insights into FAS defects underlying autoimmune lymphoproliferative syndrome revealed by studies in consanguineous patients.

PubMed

Ben-Mustapha, Imen; Agrebi, Nourhen; Barbouche, Mohamed-Ridha

2018-03-01

Autoimmune lymphoproliferative syndrome (ALPS) is a primary immunodeficiency disease due to impaired Fas-Fas ligand apoptotic pathway. It is characterized by chronic nonmalignant, noninfectious lymphadenopathy and/or splenomegaly associated with autoimmune manifestations primarily directed against blood cells. Herein, we review the heterogeneous ALPS molecular bases and discuss recent findings revealed by the study of consanguineous patients. Indeed, this peculiar genetic background favored the identification of a novel form of AR ALPS-FAS associated with normal or residual protein expression, expanding the spectrum of ALPS types. In addition, rare mutational mechanisms underlying the splicing defects of FAS exon 6 have been identified in AR ALPS-FAS with lack of protein expression. These findings will help decipher critical regions required for the tight regulation of FAS exon 6 splicing. We also discuss the genotype-phenotype correlation and disease severity in AR ALPS-FAS. Altogether, the study of ALPS molecular bases in endogamous populations helps to better classify the disease subgroups and to unravel the Fas pathway functioning. ©2017 Society for Leukocyte Biology.

The evolution and expression of the snaR family of small non-coding RNAs

PubMed Central

Parrott, Andrew M.; Tsai, Michael; Batchu, Priyanka; Ryan, Karen; Ozer, Harvey L.; Tian, Bin; Mathews, Michael B.

2011-01-01

We recently identified the snaR family of small non-coding RNAs that associate in vivo with the nuclear factor 90 (NF90/ILF3) protein. The major human species, snaR-A, is an RNA polymerase III transcript with restricted tissue distribution and orthologs in chimpanzee but not rhesus macaque or mouse. We report their expression in human tissues and their evolution in primates. snaR genes are exclusively in African Great Apes and some are unique to humans. Two novel families of snaR-related genetic elements were found in primates: CAS (catarrhine ancestor of snaR), limited to Old World Monkeys and apes; and ASR (Alu/snaR-related), present in all monkeys and apes. ASR and CAS appear to have spread by retrotransposition, whereas most snaR genes have spread by segmental duplication. snaR-A and snaR-G2 are differentially expressed in discrete regions of the human brain and other tissues, notably including testis. snaR-A is up-regulated in transformed and immortalized human cells, and is stably bound to ribosomes in HeLa cells. We infer that snaR evolved from the left monomer of the primate-specific Alu SINE family via ASR and CAS in conjunction with major primate speciation events, and suggest that snaRs participate in tissue- and species-specific regulation of cell growth and translation. PMID:20935053

Identifying mutations in Tunisian families with retinal dystrophy.

PubMed

Habibi, Imen; Chebil, Ahmed; Falfoul, Yosra; Allaman-Pillet, Nathalie; Kort, Fedra; Schorderet, Daniel F; El Matri, Leila

2016-11-22

Retinal dystrophies (RD) are a rare genetic disorder with high genetic heterogeneity. This study aimed at identifying disease-causing variants in fifteen consanguineous Tunisian families. Full ophthalmic examination was performed. Index patients were subjected to IROme analysis or whole exome sequencing followed by homozygosity mapping. All detected variations were confirmed by direct Sanger sequencing. Mutation analysis in our patients revealed two compound heterozygous mutations p.(R91W);(V172D) in RPE65, and five novel homozygous mutations: p.R765C in CNGB1, p.H337R in PDE6B, splice site variant c.1129-2A > G and c.678_681delGAAG in FAM161A and c.1133 + 3_1133 + 6delAAGT in CERKL. The latter mutation impacts pre-mRNA splicing of CERKL. The other changes detected were six previously reported mutations in CNGB3 (p.R203*), ABCA4 (p.W782*), NR2E3 (p.R311Q), RPE65 (p.H182Y), PROM1 (c.1354dupT) and EYS (c.5928-2A > G). Segregation analysis in each family showed that all affected individuals were homozygotes and unaffected individuals were either heterozygote carriers or homozygous wild type allele. These results confirm the involvement of a large number of genes in RD in the Tunisian population.

Expression and strain variation of the novel “Small Open Reading Frame” 3 (smorf) multigene family in Babesia bovis

USDA-ARS?s Scientific Manuscript database

Small open reading frame (smorf) genes comprise the second largest Babesia bovis multigene family. All known 44 variant smorf genes are located in close chromosomal proximity to ves1 genes, which encode proteins that mediate cytoadhesion and contribute to immune evasion. In this study, we characte...

Hematopoietic stem cell transplantation from non-sibling matched family donors for patients with thalassemia major in Jordan.

PubMed

Hussein, Ayad Ahmed; Al-Zaben, Abdulhadi; Khattab, Eman; Haroun, Anas; Frangoul, Haydar

2016-02-01

There are limited data on the outcome of patients with thalassemia receiving HSCT from non-sibling matched family donors. Of the 341 patients with thalassemia major that underwent donor search at our center from January 2003 to December 2011, 236 (69.2%) had fully matched family donor of which 28 patients (8.2%) had non-sibling matched family donors identified. We report on seven patients with a median age of eight yr (4-21) who underwent myeloablative (n = 4) or RIC (n = 3) HSCT. The median age of the donors was 33 yr (4-47), three were parents, two first cousins, one paternal uncle, and one paternal aunt. All patients achieved primary neutrophil and platelet engraftment at a median of 18 (13-20) and 16 days (11-20), respectively. One patient developed grade II acute GVHD, and two patients developed limited chronic GVHD. One patient experienced secondary GF requiring a second transplant. At a median follow-up of 69 months (7-110), all patients are alive and thalassemia free. Our data emphasize the need for extended family HLA typing for patients with thalassemia major in regions where there is high rate of consanguinity. Transplant from non-sibling matched family donor can result in excellent outcome. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Frameshift mutation in the APOA5 gene causing hypertriglyceridemia in a Pakistani family: Management and considerations for cardiovascular risk.

PubMed

Thériault, Sébastien; Don-Wauchope, Andrew; Chong, Michael; Lali, Ricky; Morrison, Katherine M; Paré, Guillaume

2016-01-01

We report a novel homozygous apolipoprotein A5 (APOA5) frameshift mutation (c.G425del-C, p.Arg143AlafsTer57) identified in a 12-year-old boy of Pakistani origin with severe hypertriglyceridemia (up to 35 mmol/L) and type V hyperlipoproteinemia. The patient did not respond to fibrate therapy, but his condition improved under a very low fat diet, although compliance was suboptimal. Heterozygous status was detected in both parents (consanguineous union) and one sibling, all showing moderate hypertriglyceridemia (between 5 and 10 mmol/L). There was a significant family history of premature cardiovascular disease. The index case was also diagnosed with a coronary artery anomaly. Considering the recently reported association of rare mutations in APOA5 with the risk of early myocardial infarction, we discuss the implications of these findings for the young man and his family. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Homozygosity mapping, to chromosome 11p, of the gene for familial persistent hyperinsulinemic hypoglycemia of infancy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thomas, P.M.; Cote, G.J.; Hallman, D.M.

1995-02-01

Familial persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is a rare, autosomal recessive disease of unregulated insulin secretion, defined by elevations in serum insulin despite severe hypoglycemia. We used the homozygosity gene-mapping strategy to localize this disorder to the region of chromosome 11p between markers D11S1334 and D11S899 (maximum LOD score 5.02 [{theta} = 0] at marker D11S926) in five consanguineous families of Saudi Arabian origin. These results extend those of a recent report that also placed PHHI on chromosome 11p, between markers D11S926 and D11S928. Comparison of the boundaries of these two overlapping regions allows the PHHI locus to bemore » assigned to the 4-cM region between the markers D11S926 and D11S899. Identification of this gene may allow a better understanding of other disorders of glucose homeostasis, by providing insight into the regulation of insulin release. 37 refs., 2 figs., 4 tabs.« less

A novel mutation in NDUFS4 causes Leigh syndrome in an Ashkenazi Jewish family.

PubMed

Anderson, S L; Chung, W K; Frezzo, J; Papp, J C; Ekstein, J; DiMauro, S; Rubin, B Y

2008-12-01

Leigh syndrome is a neurodegenerative disorder of infancy or childhood generally due to mutations in nuclear or mitochondrial genes involved in mitochondrial energy metabolism. We performed linkage analysis in an Ashkenazi Jewish (AJ) family without consanguinity with three affected children. Linkage to microsatellite markers D5S1969 and D5S407 led to evaluation of the complex I gene NDUFS4, in which we identified a novel homozygous c.462delA mutation that disrupts the reading frame. The resulting protein lacks a cAMP-dependent protein kinase phosphorylation site required for activation of mitochondrial respiratory chain complex I. In a random sample of 5000 healthy AJ individuals, the carrier frequency of the NDUFS4 mutation c.462delA was 1 in 1000, suggesting that it should be considered in all AJ patients with Leigh syndrome.

National impacts of the Weatherization Assistance Program in single-family and small multifamily dwellings

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, M.A.; Berry, L.G.; Balzer, R.A.

1993-05-01

Since 1976, the US Department of Energy (DOE) has operated one of the largest energy conservation programs in the nation -- the low-income Weatherization Assistance Program. The program strives to increase the energy efficiency of dwellings occupied by low-income persons in order to reduce their energy consumption, lower their fuel bills, increase the comfort of their homes, and safeguard their health. It targets vulnerable groups including the elderly, people with disabilities, and families with children. The most recent national evaluation of the impacts of the Program was completed in 1984 based on energy consumption data for households weatherized in 1981.more » DOE Program regulations and operations have changed substantially since then: new funding sources, management principles, diagnostic procedures, and weatherization technologies have been incorporated. Many of these new features have been studied in isolation or at a local level; however, no recent evaluation has assessed their combined, nationwide impacts to date or their potential for the future. In 1990, DOE initiated such an evaluation. This evaluation is comprised of three ``impact`` studies (the Single-Family Study, High-Density Multifamily Study, and Fuel-Oil Study) and two ``policy`` studies. Altogether, these five studies will provide a comprehensive national assessment of the Weatherization Assistance Program as it existed in the 1989 Program Year (PY 1989). This report presents the results of the first phase of the Single-Family Study. It evaluates the energy savings and cost effectiveness of the Program as it has been applied to the largest portion of its client base -- low-income households that occupy single-family dwellings, mobile homes, and small (2- to 4-unit) multifamily dwellings. It is based upon a representative national sample that covers the full range of conditions under which the program was implemented in PY 1989.« less

Evaluation of a Teaching Kit for Family and Consumer Science Classrooms: Motivating Students to Use a Food Thermometer with Small Cuts of Meat

ERIC Educational Resources Information Center

Edwards, Zena; Edlefsen, Miriam; Hillers, Virginia; McCurdy, Sandra M.

2005-01-01

The U.S. Dept. of Agriculture recommends use of food thermometers to safely cook small cuts of meat, yet most consumers do not use them. Consumers lack knowledge about how and why to use food thermometers with small cuts of meat. Opportunities exist for family and consumer science classes to provide education about thermometers to adolescents, who…

Linkage and association study of late-onset Alzheimer disease families linked to 9p21.3.

PubMed

Züchner, S; Gilbert, J R; Martin, E R; Leon-Guerrero, C R; Xu, P-T; Browning, C; Bronson, P G; Whitehead, P; Schmechel, D E; Haines, J L; Pericak-Vance, M A

2008-11-01

A chromosomal locus for late-onset Alzheimer disease (LOAD) has previously been mapped to 9p21.3. The most significant results were reported in a sample of autopsy-confirmed families. Linkage to this locus has been independently confirmed in AD families from a consanguineous Israeli-Arab community. In the present study we analyzed an expanded clinical sample of 674 late-onset AD families, independently ascertained by three different consortia. Sample subsets were stratified by site and autopsy-confirmation. Linkage analysis of a dense array of SNPs across the chromosomal locus revealed the most significant results in the 166 autopsy-confirmed families of the NIMH sample. Peak HLOD scores of 4.95 at D9S741 and 2.81 at the nearby SNP rs2772677 were obtained in a dominant model. The linked region included the cyclin-dependent kinase inhibitor 2A gene (CDKN2A), which has been suggested as an AD candidate gene. By re-sequencing all exons in the vicinity of CDKN2A in 48 AD cases, we identified and genotyped four novel SNPs, including a non-synonymous, a synonymous, and two variations located in untranslated RNA sequences. Family-based allelic and genotypic association analysis yielded significant results in CDKN2A (rs11515: PDT p = 0.003, genotype-PDT p = 0.014). We conclude that CDKN2A is a promising new candidate gene potentially contributing to AD susceptibility on chromosome 9p.

Homozygosity mapping of a third Joubert syndrome locus to 6q23

PubMed Central

Lagier-Tourenne, C; Boltshauser, E; Breivik, N; Gribaa, M; Betard, C; Barbot, C; Koenig, M

2004-01-01

Background: Joubert syndrome (JS) is a recessively inherited disorder characterised by hypotonia at birth and developmental delay, followed by truncal ataxia and cognitive impairment, characteristic neuroimaging findings (cerebellar vermis hypoplasia, "molar tooth sign") and suggestive facial features. JS is clinically heterogeneous with some patients presenting with breathing abnormalities in the neonatal period, oculomotor apraxia, retinal dystrophy, retinal coloboma, ptosis, hexadactyly, and nephronophtisis or cystic dysplastic kidneys. JS is also genetically heterogeneous, with two known loci, on 9q34 (JBTS1) and 11p11-q12 (CORS2), representing only a fraction of cases. Methods: A large consanguineous Joubert family (five affected) was analysed for linkage with a marker set covering the entire genome and 16 smaller families were subsequently tested for candidate loci. Results: We report here the identification of a third locus in 6q23 (JBTS3) from the study of two consanguineous families. LOD score calculation, including the consanguinity loops, gave a maximum value of 4.1 and 2.3 at q = 0 for the two families, respectively. Conclusions: Linkage between the disease and the D6S1620–D6S1699 haplotype spanning a 13.1 cM interval is demonstrated. Genotype-phenotype studies indicate that, unlike CORS2, JBTS3 appears not to be associated with renal dysfunction. PMID:15060101

Conserved Lipid and Small-Molecule Modulation of COQ8 Reveals Regulation of the Ancient Kinase-like UbiB Family.

PubMed

Reidenbach, Andrew G; Kemmerer, Zachary A; Aydin, Deniz; Jochem, Adam; McDevitt, Molly T; Hutchins, Paul D; Stark, Jaime L; Stefely, Jonathan A; Reddy, Thiru; Hebert, Alex S; Wilkerson, Emily M; Johnson, Isabel E; Bingman, Craig A; Markley, John L; Coon, Joshua J; Dal Peraro, Matteo; Pagliarini, David J

2018-02-15

Human COQ8A (ADCK3) and Saccharomyces cerevisiae Coq8p (collectively COQ8) are UbiB family proteins essential for mitochondrial coenzyme Q (CoQ) biosynthesis. However, the biochemical activity of COQ8 and its direct role in CoQ production remain unclear, in part due to lack of known endogenous regulators of COQ8 function and of effective small molecules for probing its activity in vivo. Here, we demonstrate that COQ8 possesses evolutionarily conserved ATPase activity that is activated by binding to membranes containing cardiolipin and by phenolic compounds that resemble CoQ pathway intermediates. We further create an analog-sensitive version of Coq8p and reveal that acute chemical inhibition of its endogenous activity in yeast is sufficient to cause respiratory deficiency concomitant with CoQ depletion. Collectively, this work defines lipid and small-molecule modulators of an ancient family of atypical kinase-like proteins and establishes a chemical genetic system for further exploring the mechanistic role of COQ8 in CoQ biosynthesis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Novel mutation in TSPAN12 leads to autosomal recessive inheritance of congenital vitreoretinal disease with intra-familial phenotypic variability.

PubMed

Gal, Moran; Levanon, Erez Y; Hujeirat, Yasir; Khayat, Morad; Pe'er, Jacob; Shalev, Stavit

2014-12-01

Developmental malformations of the vitreoretinal vasculature are a heterogeneous group of conditions with various modes of inheritance, and include familial exudative vitreoretinopathy (FEVR), persistent fetal vasculature (PFV), and Norrie disease. We investigated a large consanguineous kindred with multiple affected individuals exhibiting variable phenotypes of abnormal vitreoretinal vasculature, consistent with the three above-mentioned conditions and compatible with autosomal recessive inheritance. Exome sequencing identified a novel c.542G > T (p.C181F) apparently mutation in the TSPAN12 gene that segregated with the ocular disease in the family. The TSPAN12 gene was previously reported to cause dominant and recessive FEVR, but has not yet been associated with other vitreoretinal manifestations. The intra-familial clinical variability caused by a single mutation in the TSPAN12 gene underscores the complicated phenotype-genotype correlation of mutations in this gene, and suggests that there are additional genetic and environmental factors involved in the complex process of ocular vascularization during embryonic development. Our study supports considering PFV, FEVR, and Norrie disease a spectrum of disorders, with clinical and genetic overlap, caused by mutations in distinct genes acting in the Norrin/β-catenin signaling pathway. © 2014 Wiley Periodicals, Inc.

Family Portrait of the Small Inner Satellites of Jupiter

NASA Technical Reports Server (NTRS)

1997-01-01

These images, taken by Galileo's solid state imaging system between November 1996 and June 1997, provide the first ever 'family portrait' of the four small, irregularly shaped moons that orbit Jupiter in the zone between the planet's ring and the larger Galilean satellites. The moons are shown in their correct relative sizes, with north approximately up in all cases. From left to right, arranged in order of increasing distance from Jupiter, are Metis (longest dimension is approximately 60 kilometers or 37 miles across), Adrastea (20 kilometers or 12 miles across), Amalthea (247 kilometers or 154 miles across), and Thebe (116 kilometers or 72 miles across). While Amalthea, the largest of these four tiny moons, was imaged by NASA's two Voyager spacecraft in 1979 with a resolution comparable to what is shown here, the new Galileo observations represent the first time that Metis, Adrastea, and Thebe have been seen as more than points of light.

The Jet Propulsion Laboratory, Pasadena, CA manages the Galileo mission for NASA's Office of Space Science, Washington, DC. JPL is an operating division of California Institute of Technology (Caltech).

This image and other images and data received from Galileo are posted on the World Wide Web, on the Galileo mission home page at URL http://www.jpl.nasa.gov/ galileo.

The relationship between periodontal status and peripheral levels of neutrophils in two consanguineous siblings with severe congenital neutropenia: case reports.

PubMed

Tözüm, Tolga Fikret; Berker, Ezel; Ersoy, Fügen; Tezcan, Iihan; Sanal, Ozden

2003-03-01

Congenital neutropenia is characterized by a severe reduction in absolute neutrophil counts, resulting in an almost total absence of neutrophils. It is well known that severe neutropenia affects periodontal status. Oral manifestations include ulcerations, gingival desquamation, gingival inflammation, attachment loss, and alveolar bone loss which may result in tooth loss. Treatment with granulocyte-colony stimulating factor (G-CSF) may improve this periodontal condition. This article reports the relationship between periodontal disease status and peripheral neutrophil levels in two consanguineous siblings with severe congenital neutropenia who did not receive routine G-CSF for 2 years prior to examination. Both siblings were given scaling, root planing, and periodontal prophylaxis in regular follow-up visits. This report demonstrates that periodontal therapy supported by adequate oral hygiene may result in restoration of neutrophil counts in siblings with congenital neutropenia.

Changes in American Family Life

ERIC Educational Resources Information Center

Norton, Arthur J.; Glick, Paul C.

1976-01-01

This article attempts to provide a factual, historical perspective on the current family situation of American children. Demographic statistics from recent decades are given which show trends toward small family size, nuclear families, one-parent families, and a higher level of education among parents. (MS)

Molecular analysis of Hurler syndrome in Druze and Muslim Arab patients in Israel: Multiple allelic mutations of the IDUA gene in a small geographic area

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bach, G.; Moskowitz, S.M.; Tieu, P.T.

1993-08-01

The mutations underlying Hurler syndrome (mucopolysaccharidosis IH) in Druze and Muslim Israeli Arab patients have been characterized. Four alleles were identified, using a combination of (a) PCR amplification of reverse-transcribed RNA or genomic DNA segments, (b) cycle sequencing of PCR products, and (c) restriction-enzyme analysis. One allele has two amino acid substitutions, Gly[sub 409][yields]Arg in exon 9 and Ter[yields]Cys in exon 14. The other three alleles have mutations in exon 2 (Tyr[sub 64][yields]Ter), exon 7 (Gln[sub 310][yields]Ter), or exon 8 (Thr[sub 366][yields]Pro). Transfection of mutagenized cDNAs into Cos-1 cells showed that two missense mutations, Thr[sub 366][yields]Pro and Ter[yields]Cys, permitted themore » expression of only trace amounts of [alpha]-L-iduronidase activity, whereas Gly[sub 409][yields]Arg permitted the expression of 60% as much enzyme as did the normal cDNA. The nonsense mutations were associated with abnormalities of RNA processing: (1) both a very low level of mRNA and skipping of exon 2 for Tyr[sub 64][yields]Ter and (2) utilization of a cryptic splice site for Gln[sub 310][yields]Ter. In all instances, the probands were found homozygous, and the parents heterozygous, for the mutant alleles, as anticipated from the consanguinity in each family. The two-mutation allele was identified in a family from Gaza; the other three alleles were found in seven families, five of them Druze, residing in a very small area of northern Israel. Since such clustering suggests a classic founder effect, the presence of three mutant alleles of the IDUA gene was unexpected. 28 refs., 4 figs., 3 tabs.« less

Familial transmission of schizophrenia in Palau: A 20-year genetic epidemiological study in three generations.

PubMed

Myles-Worsley, Marina; Tiobech, Josepha; Blailes, Francisca; Middleton, Frank A; Vinogradov, Sophia; Byerley, William; Faraone, Stephen V

2011-04-01

Our genetic epidemiological studies of schizophrenia and other psychotic disorders (SCZ) in the isolated population of Palau have been ongoing for 20 years. Results from the first decade showed that Palau has an elevated prevalence of SCZ and that cases cluster in extended multigenerational pedigrees interconnected via complex genetic relationships after centuries of endogamous, but not consanguineous, marriages. The aim of our second decade of research, which extended data collection into a third generation of young, high-risk (HR) Palauans, was to identify significant predictors of intergenerational transmission of illness. Our findings revealed that degree of familial loading and gender effects on reproductive fitness are important modifiers of risk for transmission of SCZ. Among 45 distinct multiplex families, we identified 10 high-density (HD) Palauan families, each with 7-29 SCZ cases, which contain half of Palau's 260 SCZ cases and 80% of the 113 SCZ cases with one or more affected first-degree relatives, indicating that familial loading is a major risk factor for SCZ in Palau. Cases that belong to multiply affected sibships are more common than cases with an affected parent. Furthermore, only 6/38 multiply affected sibships have an affected parent, strong evidence that many unaffected parents are obligate carriers of susceptibility genes. Although reproductive fitness is dramatically reduced in affected males, the 30% minority who do become fathers are twice as likely as affected mothers to transmit SCZ to an offspring. As they evolve, these HD families can help to elucidate the genetic mechanisms that predict intergenerational transmission of SCZ. Copyright © 2011 Wiley-Liss, Inc.

SLC52A2 mutations cause SCABD2 phenotype: A second report.

PubMed

Babanejad, Mojgan; Adeli, Omid Ali; Nikzat, Nooshin; Beheshtian, Maryam; Azarafra, Hakimeh; Sadeghnia, Farnaz; Mohseni, Marzieh; Najmabadi, Hossein; Kahrizi, Kimia

2018-01-01

Autosomal recessive cerebellar ataxias (ARCAs) are a large group of neurodegenerative disorders that manifest mainly in children and young adults. Most ARCAs are heterogeneous with respect to age at onset, severity of disease progression, and frequency of extracerebellar and systemic signs. The phenotype of a consanguineous Iranian family was characterized using clinical testing and pedigree analysis. Whole-exome sequencing was used to identify the disease-causing gene in this family. Using whole exome sequencing (WES), a novel missense mutation in SLC52A2 gene is reported in a consanguineous Iranian family with progressive severe hearing loss, optic atrophy and ataxia. This is the second report of the genotype-phenotype correlation between this syndrome named spinocerebellar ataxia with blindness and deafness type 2 (SCABD2) and SLC52A2 gene. Copyright © 2017 Elsevier B.V. All rights reserved.

Space weathering of small Koronis family members

NASA Astrophysics Data System (ADS)

Thomas, Cristina A.; Rivkin, Andrew S.; Trilling, David E.; Enga, Marie-therese; Grier, Jennifer A.

2011-03-01

The space weathering process and its implications for the relationships between S- and Q-type asteroids and ordinary chondrite meteorites is an often debated topic in asteroid science. Q-type asteroids have been shown to display the best spectral match to ordinary chondrites (McFadden, L.A., Gaffey, M.J., McCord, T.B. [1985]. Science 229, 160-163). While the Q-types and ordinary chondrites share some spectral features with S-type asteroids, the S-types have significantly redder spectral slopes than the Q-types in visible and near-infrared wavelengths. This reddening of spectral slope is attributed to the effects of space weathering on the observed surface composition. The analysis by Binzel et al. (Binzel, R.P., Rivkin, A.S., Stuart, J.S., Harris, A.W., Bus, S.J., Burbine, T.H. [2004]. Icarus 170, 259-294) provided a missing link between the Q- and S-type bodies in near-Earth space by showing a reddening of spectral slope in objects from 0.1 to 5 km that corresponded to a transition from Q-type to S-type asteroid spectra, implying that size, and therefore surface age, is related to the relationship between S- and Q-types. The existence of Q-type asteroids in the main-belt was not confirmed until Mothé-Diniz and Nesvorny (Mothé-Diniz, T., Nesvorny, D. [2008]. Astron. Astrophys. 486, L9-L12) found them in young S-type clusters. The young age of these families suggest that the unweathered surface could date to the formation of the family. This leads to the question of whether older S-type main-belt families can contain Q-type objects and display evidence of a transition from Q- to S-type. To answer this question we have carried out a photometric survey of the Koronis family using the Kitt Peak 2.1 m telescope. This provides a unique opportunity to compare the effects of the space weathering process on potentially ordinary chondrite-like bodies within a population of identical initial conditions. We find a trend in spectral slope for objects 1-5 km that shows the

The Quality of Teachers' Interactive Conversations with Preschool Children from Low-Income Families during Small-Group and Large-Group Activities

ERIC Educational Resources Information Center

Chen, Jennifer J.; de Groot Kim, Sonja

2014-01-01

This study examined the quality of preschool teachers' interactive conversations with three- and four-year-olds in two Head Start classrooms serving children from low-income families in the United States. Over a period of 20?weeks, 10 bi-weekly observations of conversations (totaling 15?h per classroom) were conducted in one small-group (Play…

Age distribution of human gene families shows significant roles of both large- and small-scale duplications in vertebrate evolution.

PubMed

Gu, Xun; Wang, Yufeng; Gu, Jianying

2002-06-01

The classical (two-round) hypothesis of vertebrate genome duplication proposes two successive whole-genome duplication(s) (polyploidizations) predating the origin of fishes, a view now being seriously challenged. As the debate largely concerns the relative merits of the 'big-bang mode' theory (large-scale duplication) and the 'continuous mode' theory (constant creation by small-scale duplications), we tested whether a significant proportion of paralogous genes in the contemporary human genome was indeed generated in the early stage of vertebrate evolution. After an extensive search of major databases, we dated 1,739 gene duplication events from the phylogenetic analysis of 749 vertebrate gene families. We found a pattern characterized by two waves (I, II) and an ancient component. Wave I represents a recent gene family expansion by tandem or segmental duplications, whereas wave II, a rapid paralogous gene increase in the early stage of vertebrate evolution, supports the idea of genome duplication(s) (the big-bang mode). Further analysis indicated that large- and small-scale gene duplications both make a significant contribution during the early stage of vertebrate evolution to build the current hierarchy of the human proteome.

To integrate family planning into the building up of mental civilization by offering comprehensive services.

PubMed

1988-03-01

The government of Nangong City, a newly instituted city with a relatively large proportion of agricultural workers has integrated family planning into the building up of mental civilization. As a result, in 1986, the family planning practice rate was 98.4%. One way the government accomplished this was by developing production to eliminate poverty, to show that population development has a significant impact on socioeconomic development. To help change people's attitudes about family planning, the government 1) used publicity, such as speechmaking, mass media, and courses in population theory; 2) awarded those who made contributions; 3) carried out publicity and education in accordance with characteristics of different groups of people; and 4) encouraged bridegrooms to live with their wives' families if the wives' parents had had no son. Another technique the government used as the popularization of scientific knowledge about population theory, physiology and hygiene, birth control, and eugenics and health in births. A 4th method was to popularize knowledge of laws and regulations, such as of early marriage and consanguineous marriage. 5th, the government developed social security undertakings: 1) giving priority to single-child families and 2) taking care of the elderly. Finally, the government improved maternal and child care by 1) providing premarital health care; 2) creating a project for healthier births and better upbringing; 3) family planning workers showing warm concern for reproductive women; and 4) controlling women's diseases and providing health care knowledge, as well as family planning services. These 6 activities have resulted in 1) the decreasing momentum of per capita arable land being controlled, 2) 1-child couples having more time to learn, 3) the development of educational undertakings, 4) a change in people's traditional practices, and 5) improvement in the understanding of patriotism.

Female sex, small size at birth and low family income increase the likelihood of insulin resistance in late childhood: the Healthy Growth Study.

PubMed

Manios, Yannis; Moschonis, George; Papandreou, Christopher; Siatitsa, Paraskevi-Eirini; Iatridi, Vassiliki; Lidoriki, Irene; Lionis, Christos; Chrousos, George P

2014-02-01

To identify among a wide range of perinatal indices, as well as certain family sociodemographic and parental characteristics, those independently associated with insulin resistance (IR) in late childhood. A representative sample of 2195 Greek schoolchildren, aged 9-13 yr, was examined, and based on the biochemical indices collected IR was estimated using the homeostasis model assessment (HOMA-IR < 3.16). Perinatal data were recorded from children's medical records, retrospectively, while family sociodemographics and parental anthropometrics were reported by parents. The overall prevalence of IR was 28.4%, with a higher prevalence observed for girls compared with boys (p <0.05). Examination of univariate associations, per se, showed that maternal current and pre-pregnancy overweight/obesity, maternal smoking at early pregnancy, children's small birth weight, and rapid growth at infancy as well as female sex and non-Caucasian race increased the likelihood of IR. In contrast, folate supplementation during pregnancy, as well as higher paternal education and annual family income decreased the likelihood of IR in children. Inclusion of all above variables at a multivariable regression model highlighted female sex [odds ratios (OR): 1.67, 95% confidence intervals (CI): 1.30-2.13], small birth weight (OR: 1.41, 95% CI: 1.03-2.01), and higher annual family income (OR: 0.71, 95% CI: 0.53-0.95 for 12 000-30 000 € and OR: 0.68, 95% CI: 0.48-0.96 for >30 000 €) as the only significant correlates of IR after also controlling for children's body mass index (BMI) and Tanner stage. The current study highlighted small birth weight and female sex as the only perinatal factors independently associated with the occurrence of IR in late childhood, when examined at a multivariable level with a wide range of perinatal indices as well as certain family sociodemographic and parental characteristics. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Mutation analysis for DJ-1 in sporadic and familial parkinsonism: screening strategy in parkinsonism.

PubMed

Tomiyama, Hiroyuki; Li, Yuanzhe; Yoshino, Hiroyo; Mizuno, Yoshikuni; Kubo, Shin-Ichiro; Toda, Tatsushi; Hattori, Nobutaka

2009-05-22

DJ-1 mutations cause autosomal recessive parkinsonism (ARP). Although some reports of DJ-1 mutations have been published, there is lack of information on the prevalence of these mutations in large-scale studies of both familial and sporadic parkinsonism. In this genetic screening study, we analyzed the distribution and frequency of DJ-1 mutations by direct nucleotide sequencing of coding exons and exon-intron boundaries of DJ-1, in 386 parkin-negative parkinsonism patients (371 index cases: 67 probands of autosomal recessive parkinsonism families, 90 probands of autosomal dominant parkinsonism families, 201 patients with sporadic parkinsonism, and 13 with unknown family histories) from 12 countries (Japan 283, China 27, Taiwan 22, Korea 22, Israel 16, Turkey 5, Philippines 2, Bulgaria 2, Greece 2, Tunisia 1, USA 2, Ukraine 1, unknown 1). None had causative mutation in DJ-1, suggesting DJ-1 mutation is very rare among patients with familial and sporadic parkinsonism from Asian countries and those with other ethnic background. This is in contrast to the higher frequencies and worldwide distribution of parkin- and PINK1-related parkinsonism in ARP and sporadic parkinsonism. Thus, after obtaining clinical information, screening for mutations in (1) parkin, (2) PINK1, (3) DJ-1, (4) ATP13A2 should be conducted in that order, in ARP and sporadic parkinsonism, based on their reported frequencies. In addition, haplotype analysis should be employed to check for homozygosity of 1p36, which harbors a cluster of causative genes for ARP such as DJ-1, PINK1 and ATP13A2 in ARP and sporadic parkinsonism, especially in parkinsonism with consanguinity.

A family of small-world network models built by complete graph and iteration-function

NASA Astrophysics Data System (ADS)

Ma, Fei; Yao, Bing

2018-02-01

Small-world networks are popular in real-life complex systems. In the past few decades, researchers presented amounts of small-world models, in which some are stochastic and the rest are deterministic. In comparison with random models, it is not only convenient but also interesting to study the topological properties of deterministic models in some fields, such as graph theory, theorem computer sciences and so on. As another concerned darling in current researches, community structure (modular topology) is referred to as an useful statistical parameter to uncover the operating functions of network. So, building and studying such models with community structure and small-world character will be a demanded task. Hence, in this article, we build a family of sparse network space N(t) which is different from those previous deterministic models. Even though, our models are established in the same way as them, iterative generation. By randomly connecting manner in each time step, every resulting member in N(t) has no absolutely self-similar feature widely shared in a large number of previous models. This makes our insight not into discussing a class certain model, but into investigating a group various ones spanning a network space. Somewhat surprisingly, our results prove all members of N(t) to possess some similar characters: (a) sparsity, (b) exponential-scale feature P(k) ∼α-k, and (c) small-world property. Here, we must stress a very screming, but intriguing, phenomenon that the difference of average path length (APL) between any two members in N(t) is quite small, which indicates this random connecting way among members has no great effect on APL. At the end of this article, as a new topological parameter correlated to reliability, synchronization capability and diffusion properties of networks, the number of spanning trees on a representative member NB(t) of N(t) is studied in detail, then an exact analytical solution for its spanning trees entropy is also

Identification of a Ninein (NIN) mutation in a family with spondyloepimetaphyseal dysplasia with joint laxity (leptodactylic type)-like phenotype.

PubMed

Grosch, Melanie; Grüner, Barbara; Spranger, Stephanie; Stütz, Adrian M; Rausch, Tobias; Korbel, Jan O; Seelow, Dominik; Nürnberg, Peter; Sticht, Heinrich; Lausch, Ekkehart; Zabel, Bernhard; Winterpacht, Andreas; Tagariello, Andreas

2013-01-01

Spondyloepimetaphyseal dysplasia with joint laxity-leptodactylic type (SEMDJL2) is an autosomal dominant skeletal dysplasia which is characterized by midface hypoplasia, short stature, joint laxity with dislocations, genua valga, progressive scoliosis, and slender fingers. Recently, heterozygous missense mutations in KIF22, a gene which encodes a member of the kinesin-like protein family, have been identified in sporadic as well as familial cases of SEMDJL2. In the present study homozygosity mapping and whole-exome sequencing were combined to analyze a consanguineous family with a phenotype resembling SEMDJL2. We identified homozygous missense mutations in the two nearby genes NIN (Ninein) and POLE2 (DNA polymerase epsilon subunit B) which segregate with the disease in the family and were not present in 500 healthy control individuals and in the 1094 control individuals contained within the 1000-genomes database. We present several lines of evidence that mutant Ninein is most likely causative for the SEMDJL2-like phenotype. The centrosomal protein NIN shows a functional relationship with KIF22 and other proteins associated with chromosome congression/movement, centrosomal function, and ciliogenesis, which have been associated with skeletal dysplasias. Moreover, compound heterozygous missense mutations at more N-terminal positions of Ninein have very recently been identified in a family with microcephalic primordial dwarfism. Together with the present report this strongly supports a fundamental role of Ninein in skeletal development. Copyright © 2013 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

[Dwarfism due to familial panhypopituitarism].

PubMed

Cos Welsh, J; Espinosa de los Monteros, A; de la Luz Ajuria, M; Morillo Almao, E

1977-01-01

Three sisters of 27 7/12, 13 8/12 and 9 1/12 years of age, respectively, with proportionate dwarfism, high pitched voice and lack of sexual development are described. All the patients had very low serum levels of immunoreactive growth hormone (GH), as well as of LH and FSH. Hypoglycemia induced by insulin and arginine infusion failed to increase GH levels, and the administration of the hypothalamic LH-FSH releasing hormone (LH-RH) did not elicit any response in the secretion of gonadotropins. The oldest sister developed hypothyroidism in recent years, since the I131 thyroid uptake was normal ten years before; her serum TSH was low and did not change with TRH stimulation. In addition, a low pituitary ACTH reserve was demonstrated by the hypoglycemia and metirapone tests. Case 2 showed partial pituitary TSH and ACTH reserve, whereas the youngest child only had low TSH pituitary reserve. These patients had all the clinical and laboratory characteristics of familial panhypopituitarism, with normal sella turcica. Genetic transmission in this cases is consistent with the autosomal recessive form, which is the most frequent type of inheritance of this entity. Consanguinity can not be ruled out. The results of the hypothalamic-pituitary functional tests apparently suggest that the primary defect could be located at the pituitary level. It is also possible that the pathological process may have a progressive evolution.

A novel homozygous HOXB1 mutation in a Turkish family with hereditary congenital facial paresis.

PubMed

Sahin, Yavuz; Güngör, Olcay; Ayaz, Akif; Güngör, Gülay; Sahin, Bedia; Yaykasli, Kursad; Ceylaner, Serdar

2017-02-01

Hereditary congenital facial paresis (HCFP) is characterized by isolated dysfunction of the facial nerve (CN VII) due to congenital cranial dysinnervation disorders. HCFP has genetic heterogeneity and HOXB1 is the first identified gene. We report the clinical, radiologic and molecular investigations of three patients admitted for HCFP in a large consanguineous Turkish family. High-throughput sequencing and Sanger sequencing of all patients revealed a novel homozygous mutation p.Arg230Trp (c.688C>T) within the HOXB1 gene. The report of the mutation brings the total number of HOXB1 mutations identified in HCFP to four. The results of this study emphasize that in individuals with congenital facial palsy accompanied by hearing loss and dysmorphic facial features, HOXB1 mutation causing HCFP should be kept in mind. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Glutaric aciduria type I in the Arab and Jewish communities in Israel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anikster, Y.; Shaag, A.; Elpeleg, O.N.

Mutation analysis was performed in eight families (16 patients) with glutaric aciduria type I (GA-I), which were all the families diagnosed in Israel in the years 1987 - 1994. Six families were of Moslem origin and two were non-Ashkenazi Jews. The entire coding region of the cDNA of the glutaryl-CoA dehydrogenase gene was sequenced in one patient of each family. Seven new mutations were identified in 15 of 16 mutated alleles, including six point mutations: T4161 (4 alleles), G39OR (1 allele), and S305L, A293T, L283P, and G101R (2 alleles each). In addition, a 1-bp deletion at position 1173 was identifiedmore » in two alleles. These findings do not provide a molecular basis for the clinical variability in GA-1 families. The occurrence of multiple novel mutations in a small geographic area may be explained by their recent onset in isolated communities with a high consanguinity rate. 22 refs., 3 figs., 3 tabs.« less

Anophthalmia-Waardenburg syndrome: a report of three cases.

PubMed

Suyugül, Z; Seven, M; Hacihanefioğlu, S; Kartal, A; Suyugül, N; Cenani, A

1996-04-24

We report on 2 Turkish families with children who had bilateral anophthalmia, upper and lower limb abnormalities, mental retardation and consanguineous parents. We have evaluated the 2 cases in the first family and the only case in the second as anophthalmia-Waardenburg syndrome. This is an extremely rare autosomal recessive syndrome.

When the mother-in-law is just as good-Differential mortality of reproductive females by family network composition.

PubMed

Willführ, Kai Pierre; Johow, Johannes; Voland, Eckart

2018-01-01

Motivated by the cooperative breeding hypothesis, we investigate the effect of having kin on the mortality of reproductive women based on family reconstitutions for the Krummhörn region (East Frisia, Germany, 1720-1874). We rely on a combination of Cox clustered hazard models and hazard models stratified at the family level. In order to study behavior-related effects, we run a series of models in which only kin who lived in the same parish are considered. To investigate structural, non-behavior-related effects, we run a different model series that include all living kin, regardless their spatial proximity. We find that women of reproductive age who had a living mother had a reduced mortality risk. It appears that having living sisters had an ambivalent impact on women's mortality: i.e., depending on the socioeconomic status of the family, the effect of having living sisters ranged between representing a source of competition and representing a source of support. Models which are clustered at the family level suggest that the presence of a living mother-in-law was associated with reduced mortality among her daughters-in-law especially among larger-scale farm families. We interpret this finding as a consequence of augmented consanguineous marriages among individuals of higher social strata. For instance, in first cousin marriages, the mother-in-law could also be a biological aunt. Thus, it appears that among the wealthy elite, the genetic in-law conflict was neutralized to some extent by family solidarity. This result further suggests that the tipping point of the female trade-off between staying with the natal family and leaving the natal family to join an economically well-established in-law family might have been reached very quickly among women living under the socioeconomic conditions of the Krummhörn region.

Normative influence and desired family size among young people in rural Egypt.

PubMed

Harbour, Catherine

2011-06-01

Research has identified the lack of acceptance of a two-child-family norm as the biggest obstacle to achieving replacement-level fertility in Egypt. This analysis examines norms about desired family size for 1,366 males and 1,367 females aged 15-24 in 2004 in rural Minya governorate. Two-level random-effects multivariate logistic regression models, stratified by sex and grouped by neighborhood, are used to assess normative influence at the household and neighborhood levels, controlling for individual- and household-level covariates. In the final model, young males in neighborhoods where more people desire a small family are 33 percent more likely to desire a small family than are young males in other neighborhoods. Young females in households with one or more adults preferring a small family are 78 percent more likely to desire a small family, and young females in households with one or more young people who prefer a small family are 37 percent more likely to desire a small family themselves, compared with those living with adults or with young people, respectively, who do not prefer a small family. Programs aiming to reduce fertility should be aware of gender differences in the sources of normative influence on desired family size.

Fragment-based discovery of a new family of non-peptidic small-molecule cyclophilin inhibitors with potent antiviral activities

PubMed Central

Ahmed-Belkacem, Abdelhakim; Colliandre, Lionel; Ahnou, Nazim; Nevers, Quentin; Gelin, Muriel; Bessin, Yannick; Brillet, Rozenn; Cala, Olivier; Douguet, Dominique; Bourguet, William; Krimm, Isabelle; Pawlotsky, Jean-Michel; Guichou, Jean- François

2016-01-01

Cyclophilins are peptidyl-prolyl cis/trans isomerases (PPIase) that catalyse the interconversion of the peptide bond at proline residues. Several cyclophilins play a pivotal role in the life cycle of a number of viruses. The existing cyclophilin inhibitors, all derived from cyclosporine A or sanglifehrin A, have disadvantages, including their size, potential for side effects unrelated to cyclophilin inhibition and drug–drug interactions, unclear antiviral spectrum and manufacturing issues. Here we use a fragment-based drug discovery approach using nucleic magnetic resonance, X-ray crystallography and structure-based compound optimization to generate a new family of non-peptidic, small-molecule cyclophilin inhibitors with potent in vitro PPIase inhibitory activity and antiviral activity against hepatitis C virus, human immunodeficiency virus and coronaviruses. This family of compounds has the potential for broad-spectrum, high-barrier-to-resistance treatment of viral infections. PMID:27652979

Familial Idiopathic Cranial Neuropathy in a Chinese Family.

PubMed

Zhang, Li; Liang, Jianfeng; Yu, Yanbing

Cranial neuropathy is usually idiopathic and familial cases are uncommon. We describe a family with 5 members with cranial neuropathy over 3 generations. All affected patients were women, indicating an X-linked dominant or an autosomal dominant mode of inheritance. Our cases and a review of the literature suggest that familial idiopathic cranial neuropathy is a rare condition which may be related to autosomal dominant vascular disorders (e.g. vascular tortuosity, sclerosis, elongation or extension), small posterior cranial fossas, anatomical variations of the posterior circulation, hypersensitivity of cranial nerves and other abnormalities. Moreover, microvascular decompression is the treatment of choice because vascular compression is the main factor in the pathogenesis. To the best of our knowledge, this is the first report of familial cranial neuropathy in China.

Spectra of small Koronis family members

NASA Astrophysics Data System (ADS)

Thomas, C.; Rivkin, A.; Trilling, D.; Moskovitz, N.

2014-07-01

The space-weathering process and its implications for the relationships between S- and Q-type asteroids and ordinary chondrite meteorites are long-standing problems in asteroid science. Although the visible and near-infrared spectra of S- and Q-type objects qualitatively show the same absorption features and quantitatively show evidence of the same minerals, the S types display increased spectral slopes and muted absorption features compared to the Q types. This spectral mismatch is consistent with the effects of the space weathering process. Binzel et al. provided the missing link between Q- and S-type bodies in near-Earth space by showing a reddening of spectral slope in objects from 0.1 to 5 km that corresponded to the transition from Q- to S-type spectra. This result implied that size, and therefore age, is related to the relationship between Q- and S-type. The existence of Q-type objects in the main belt was not confirmed until Mothe-Diniz and Nesvorny (2008) found them in young S-type clusters. To investigate the trend from Q to S in the main belt, we examined space weathering within the old main-belt Koronis family using a spectrophotometric survey (Rivkin et al. 2011, Thomas et al. 2011). Rivkin et al. (2011) identified several potential Q-type objects within the Koronis family. Our Q-type candidates were identified using broad-band spectrophotometry and could not be taxonomically classified on that basis alone. We obtained follow-up visible and near-infrared spectral observations of our potential Q-type objects, (26970) Elias, (45610) 2000 DJ_{48}, and (37411) 2001 XF_{152}, using Gemini and Magellan. We will present the results of these spectral follow-up observations. Observations of (26970) Elias demonstrate that the object is more consistent with the average Q-type spectrum than the average S-type spectrum.

Genetic assessment and folate receptor autoantibodies in infantile-onset cerebral folate deficiency (CFD) syndrome.

PubMed

Ramaekers, V Th; Segers, K; Sequeira, J M; Koenig, M; Van Maldergem, L; Bours, V; Kornak, U; Quadros, E V

2018-05-01

Cerebral folate deficiency (CFD) syndromes are defined as neuro-psychiatric conditions with low CSF folate and attributed to different causes such as autoantibodies against the folate receptor-alpha (FR) protein that can block folate transport across the choroid plexus, FOLR1 gene mutations or mitochondrial disorders. High-dose folinic acid treatment restores many neurologic deficits. Among 36 patients from 33 families the infantile-onset CFD syndrome was diagnosed based on typical clinical features and low CSF folate. All parents were healthy. Three families had 2 affected siblings, while parents from 4 families were first cousins. We analysed serum FR autoantibodies and the FOLR1 and FOLR2 genes. Among three consanguineous families homozygosity mapping attempted to identify a monogenetic cause. Whole exome sequencing (WES) was performed in the fourth consanguineous family, where two siblings also suffered from polyneuropathy as an atypical finding. Boys (72%) outnumbered girls (28%). Most patients (89%) had serum FR autoantibodies fluctuating over 5-6 weeks. Two children had a genetic FOLR1 variant without pathological significance. Homozygosity mapping failed to detect a single autosomal recessive gene. WES revealed an autosomal recessive polynucleotide kinase 3´phosphatase (PNKP) gene abnormality in the siblings with polyneuropathy. Infantile-onset CFD was characterized by serum FR autoantibodies as its predominant pathology whereas pathogenic FOLR1 gene mutations were absent. Homozygosity mapping excluded autosomal recessive inheritance of any single responsible gene. WES in one consanguineous family identified a PNKP gene abnormality that explained the polyneuropathy and also its contribution to the infantile CFD syndrome because the PNKP gene plays a dual role in both neurodevelopment and immune-regulatory function. Further research for candidate genes predisposing to FRα-autoimmunity is suggested to include X-chromosomal and non-coding DNA regions

New evidence for the role of calpain 10 in autosomal recessive intellectual disability: identification of two novel nonsense variants by exome sequencing in Iranian families.

PubMed

Oladnabi, Morteza; Musante, Luciana; Larti, Farzaneh; Hu, Hao; Abedini, Seyedeh Sedigheh; Wienker, Thomas; Ropers, Hans Hilger; Kahrizi, Kimia; Najmabadi, Hossein

2015-03-01

Knowledge of the genes responsible for intellectual disability, particularly autosomal recessive forms, is rapidly expanding. Increasing numbers of the gene show great heterogeneity and supports the hypothesis that human genome may contain over 2000 causative genes with a critical role in brain development. Since 2004, we have applied genome-wide SNP genotyping and next-generation sequencing in large consanguineous Iranian families with intellectual disability, to identify the genes harboring disease-causing mutations. The current study paved the way for identification of responsible genes in two unrelated Iranian families. We found two novel nonsense mutations, p.C77* and p.Q115*, in the calpain catalytic domain of CAPN10, which is a cysteine protease known to be involved in pathogenesis of noninsulin-dependent diabetes mellitus. Another different mutation in this gene (p.S138_R139ins5) has previously been reported in an Iranian family. All of these patients have common clinical features in spite of specific brain structural abnormalities on MRI. Different mutations in CAPN10 have already been found in three independent Iranian families. These results have strongly supported the possible role of CAPN10 in human brain development. Altogether, we proposed CAPN10 as a promising candidate gene for intellectual disability, which should be considered in diagnostic gene panels.

IFT27, encoding a small GTPase component of IFT particles, is mutated in a consanguineous family with Bardet–Biedl syndrome

PubMed Central

Aldahmesh, Mohammed A.; Li, Yuanyuan; Alhashem, Amal; Anazi, Shams; Alkuraya, Hisham; Hashem, Mais; Awaji, Ali A.; Sogaty, Sameera; Alkharashi, Abdullah; Alzahrani, Saeed; Al Hazzaa, Selwa A.; Xiong, Yong; Kong, Shanshan; Sun, Zhaoxia; Alkuraya, Fowzan S.

2014-01-01

Bardet–Biedl syndrome (BBS) is an autosomal recessive ciliopathy with multisystem involvement. So far, 18 BBS genes have been identified and the majority of them are essential for the function of BBSome, a protein complex involved in transporting membrane proteins into and from cilia. Yet defects in the identified genes cannot account for all the BBS cases. The genetic heterogeneity of this disease poses significant challenge to the identification of additional BBS genes. In this study, we coupled human genetics with functional validation in zebrafish and identified IFT27 as a novel BBS gene (BBS19). This is the first time an intraflagellar transport (IFT) gene is implicated in the pathogenesis of BBS, highlighting the genetic complexity of this disease. PMID:24488770

Further Validation of the SIGMAR1 c.151+1G>T Mutation as Cause of Distal Hereditary Motor Neuropathy

PubMed Central

Lee, Jessica J. Y.; Drögemoller, Britt; Shyr, Casper; Tarailo-Graovac, Maja; Eydoux, Patrice; Ross, Colin J.; Wasserman, Wyeth W.; Björnson, Bruce; Wu, John K.

2016-01-01

Distal hereditary motor neuropathies represent a group of rare genetic disorders characterized by progressive distal motor weakness without sensory loss. Their genetic heterogeneity is high and thus eligible for diagnostic whole exome sequencing. The authors report successful application of whole exome sequencing in diagnosing a second consanguineous family with distal hereditary motor neuropathy due to a homozygous c.151+1G>T variant in SIGMAR1. This variant was recently proposed as causal for the same condition in a consanguineous Chinese family. Compared to this family, the Afghan ethnic origin of our patient is distinct, yet the features are identical, validating the SIGMAR1 deficiency phenotype: progressive muscle wasting/weakness in lower and upper limbs without sensory loss. Rapid disease progression during adolescent growth is similar and may be due to SIGMAR1’s role in regulating axon elongation and tau phosphorylation. Finally, the authors conclude that SIGMAR1 deficiency should be added to the differential diagnosis of distal hereditary motor neuropathies. PMID:28503617

A SIGMAR1 splice-site mutation causes distal hereditary motor neuropathy.

PubMed

Li, Xiaobo; Hu, Zhengmao; Liu, Lei; Xie, Yongzhi; Zhan, Yajing; Zi, Xiaohong; Wang, Junling; Wu, Lixiang; Xia, Kun; Tang, Beisha; Zhang, Ruxu

2015-06-16

To identify the underlying genetic cause in a consanguineous Chinese family segregating distal hereditary motor neuropathy (dHMN) in an autosomal recessive pattern. We used whole-exome sequencing and homozygosity mapping to detect the genetic variant in 2 affected individuals of the consanguineous Chinese family with dHMN. RNA analysis of peripheral blood leukocytes and immunofluorescence and immunoblotting of stable cell lines were performed to support the pathogenicity of the identified mutation. We identified 3 shared novel homozygous variants in 3 shared homozygous regions of the affected individuals. Sequencing of these 3 variants in family members revealed the c.151+1G>T mutation in SIGMAR1 gene, which located in homozygous region spanning approximately 5.3 Mb at chromosome 9p13.1-p13.3, segregated with the dHMN phenotype. The mutation causes an alternative splicing event and generates a transcript variant with an in-frame deletion of 60 base pairs in exon 1 (c.92_151del), and results in an internally shortened protein σ1R(31_50del). The proteasomal inhibitor treatment increased the intracellular amount of σ1R(31_50del) and led to the formation of nuclear aggregates. Stable expressing σ1R(31_50del) induced endoplasmic reticulum stress and enhanced apoptosis. The homozygous c.151+1G>T mutation in SIGMAR1 caused a novel form of autosomal recessive dHMN in a Chinese consanguineous family. Endoplasmic reticulum stress may have a role in the pathogenesis of dHMN. © 2015 American Academy of Neurology.

[Family planning in Benin: what future?].

PubMed

Danlodji, R

1993-01-01

In Benin, family planning began in the late 1960s, but its activities were not clear or specific. It made small strides in private clinics until a family planning association was formed, later named the Beninese Association to Promote the Family (ABPF). Family planning promoters maintain that reduction in births per couple is necessary for economic development in Africa. Family planning detractors think that a child is a fruit of God and that family planning impedes his or her coming to the world. ABPF has worked much to promote Beninese families, but it is still not well known. Despite the associations efforts and those of many other institutions, contraceptive prevalence is low and the abortion rate and its risks remain high, namely, death, infertility, and contraction of various diseases. Thus, it is important to rethink family planning strategies. All intervening parties should coordinate activities to better reach urban and rural populations. Many rural inhabitants go to cities to escape poverty and the misery evoked by their family size and meager earnings only to find unemployment in the cities. In order for family planning to have an effect in Benin, it is important to begin working with youth. Any family planning strategy must consider their aspirations. The youth are inclined to be more receptive to family planning than the adults who do not want to give up old habits. Yet, contraceptive use in 14-20 year olds is low even though sexual activity is high. Since the youth want a small family size, a small plot of land, a care, and a successful life, it is important to give priority to jobs. We need to educate the youth so they can freely decide their family size. Socioeconomic reasons are the primary factor pushing people to accept family planning, followed by health reasons. Research is needed to learn why contraceptive prevalence is still low.

Severe congenital muscular dystrophy in a Mexican family with a new nonsense mutation (R2578X) in the laminin alpha-2 gene.

PubMed

Coral-Vazquez, Ramon M; Rosas-Vargas, Haydee; Meza-Espinosa, Pedro; Mendoza, Irma; Huicochea, Juan C; Ramon, Guillermo; Salamanca, Fabio

2003-01-01

The congenital muscular dystrophies (CMDs) are a heterogeneous group of autosomal recessive disorders. Approximately one half of cases diagnosed with classic CMD show primary deficiency of the laminin alpha2 chain of merosin. Complete absence of this protein is usually associated with a severe phenotype characterized by drastic muscle weakness and characteristic changes in white matter in cerebral magnetic resonance imaging (MRI). Here we report an 8-month-old Mexican female infant, from a consanguineous family, with classical CMD. Serum creatine kinase was elevated, muscle biopsy showed dystrophic changes, and there were abnormalities in brain MRI. Immunofluorescence analysis demonstrated the complete absence of laminin alpha2. In contrast, expression of alpha-, beta-, gamma-, and delta-sarcoglycans and dystrophin, all components of the dystrophin-glycoprotein complex, appeared normal. A homozygous C long right arrow T substitution at position 7781 that generated a stop codon in the G domain of the protein was identified by mutation analysis of the laminin alpha2 gene ( LAMA2). Sequence analysis on available DNA samples of the family showed that parents and other relatives were carriers of the mutation.

Familial neonatal isolated cardiomyopathy caused by a mutation in the flavoprotein subunit of succinate dehydrogenase

PubMed Central

Levitas, Aviva; Muhammad, Emad; Harel, Gali; Saada, Ann; Caspi, Vered Chalifa; Manor, Esther; Beck, John C; Sheffield, Val; Parvari, Ruti

2010-01-01

Cardiomyopathies are common disorders resulting in heart failure; the most frequent form is dilated cardiomyopathy (DCM), which is characterized by dilatation of the left or both ventricles and impaired systolic function. DCM causes considerable morbidity and mortality, and is one of the major causes of sudden cardiac death. Although about one-third of patients are reported to have a genetic form of DCM, reported mutations explain only a minority of familial DCM. Moreover, the recessive neonatal isolated form of DCM has rarely been associated with a mutation. In this study, we present the association of a mutation in the SDHA gene with recessive neonatal isolated DCM in 15 patients of two large consanguineous Bedouin families. The cardiomyopathy is presumably caused by the significant tissue-specific reduction in SDH enzymatic activity in the heart muscle, whereas substantial activity is retained in the skeletal muscle and lymphoblastoid cells. Notably, the same mutation was previously reported to cause a multisystemic failure leading to neonatal death and Leigh's syndrome. This study contributes to the molecular characterization of a severe form of neonatal cardiomyopathy and highlights extreme phenotypic variability resulting from a specific missense mutation in a nuclear gene encoding a protein of the mitochondrial respiratory chain. PMID:20551992

Familial neonatal isolated cardiomyopathy caused by a mutation in the flavoprotein subunit of succinate dehydrogenase.

PubMed

Levitas, Aviva; Muhammad, Emad; Harel, Gali; Saada, Ann; Caspi, Vered Chalifa; Manor, Esther; Beck, John C; Sheffield, Val; Parvari, Ruti

2010-10-01

Cardiomyopathies are common disorders resulting in heart failure; the most frequent form is dilated cardiomyopathy (DCM), which is characterized by dilatation of the left or both ventricles and impaired systolic function. DCM causes considerable morbidity and mortality, and is one of the major causes of sudden cardiac death. Although about one-third of patients are reported to have a genetic form of DCM, reported mutations explain only a minority of familial DCM. Moreover, the recessive neonatal isolated form of DCM has rarely been associated with a mutation. In this study, we present the association of a mutation in the SDHA gene with recessive neonatal isolated DCM in 15 patients of two large consanguineous Bedouin families. The cardiomyopathy is presumably caused by the significant tissue-specific reduction in SDH enzymatic activity in the heart muscle, whereas substantial activity is retained in the skeletal muscle and lymphoblastoid cells. Notably, the same mutation was previously reported to cause a multisystemic failure leading to neonatal death and Leigh's syndrome. This study contributes to the molecular characterization of a severe form of neonatal cardiomyopathy and highlights extreme phenotypic variability resulting from a specific missense mutation in a nuclear gene encoding a protein of the mitochondrial respiratory chain.

Consistent Small-Sample Variances for Six Gamma-Family Measures of Ordinal Association

ERIC Educational Resources Information Center

Woods, Carol M.

2009-01-01

Gamma-family measures are bivariate ordinal correlation measures that form a family because they all reduce to Goodman and Kruskal's gamma in the absence of ties (1954). For several gamma-family indices, more than one variance estimator has been introduced. In previous research, the "consistent" variance estimator described by Cliff and…

Short stature in carriers of recessive mutation causing familial isolated growth hormone deficiency.

PubMed

Leiberman, E; Pesler, D; Parvari, R; Elbedour, K; Abdul-Latif, H; Brown, M R; Parks, J S; Carmi, R

2000-01-31

Isolated growth hormone deficiency (IGHD) IB is an autosomal recessive disorder characterized by a good response to exogenous growth hormone (GH) treatment without development of anti-GH antibodies. Patients with IGHD IB were found to be compound heterozygotes for deletion and frameshift mutations as well as homozygotes for splicing mutations in the GH-1 gene. Recently, a novel splicing mutation in the GH-1 gene was identified in an extended, consanguineous Arab-Bedouin family from Israel with IGHD IB. Prior to the identification of this mutation, a considerable number of children with short stature in this family were found normal on pharmacological stimulation for GH release. This observation prompted a genotype/phenotype correlation of potential heterozygotes in the family. Carriers of the mutant GH-1 allele were found as a group to have a significantly shorter stature than normal homozygote (mean standard deviation scores, 1.67 and -0.40, respectively, P<0.05). Moreover, 11 of 33 (33%) heterozygotes, but only 1 of 17 (5.9%) normal homozygotes, had their height at 2 or more SD below the mean. Overall, 48.5% of studied heterozygotes were found to be of appreciably short stature with height at or lower than the 5th centile (> or = -1.7 SD), whereas only 5.9% of the normal homozygotes did (P<0.004). This phenomenon of heterozygotes for a recessive mutation in the GH-1 gene manifesting short stature, might imply that some such mutations may account for non-GH deficiency reduced height in the general population.

STAG3 truncating variant as the cause of primary ovarian insufficiency

PubMed Central

Le Quesne Stabej, Polona; Williams, Hywel J; James, Chela; Tekman, Mehmet; Stanescu, Horia C; Kleta, Robert; Ocaka, Louise; Lescai, Francesco; Storr, Helen L; Bitner-Glindzicz, Maria; Bacchelli, Chiara; Conway, Gerard S

2016-01-01

Primary ovarian insufficiency (POI) is a distressing cause of infertility in young women. POI is heterogeneous with only a few causative genes having been discovered so far. Our objective was to determine the genetic cause of POI in a consanguineous Lebanese family with two affected sisters presenting with primary amenorrhoea and an absence of any pubertal development. Multipoint parametric linkage analysis was performed. Whole-exome sequencing was done on the proband. Linkage analysis identified a locus on chromosome 7 where exome sequencing successfully identified a homozygous two base pair duplication (c.1947_48dupCT), leading to a truncated protein p.(Y650Sfs*22) in the STAG3 gene, confirming it as the cause of POI in this family. Exome sequencing combined with linkage analyses offers a powerful tool to efficiently find novel genetic causes of rare, heterogeneous disorders, even in small single families. This is only the second report of a STAG3 variant; the first STAG3 variant was recently described in a phenotypically similar family with extreme POI. Identification of an additional family highlights the importance of STAG3 in POI pathogenesis and suggests it should be evaluated in families affected with POI. PMID:26059840

Family Child Care as a Small Business. ECE/CDA Training Series.

ERIC Educational Resources Information Center

Huhn, Susan

This Child Development Associate training module explores the multifaceted aspects of family child care, including zoning, certification, insurance, hours of care, fees, advertising, programming, and parent/provider agreements. The module's purpose is to help individuals interested in a career in family child care understand the CDA requirements…

Impact of family history of cancer on the incidence of mutation in epidermal growth factor receptor gene in non-small cell lung cancer patients.

PubMed

He, Yayi; Li, Shuai; Ren, Shengxiang; Cai, Weijing; Li, Xuefei; Zhao, Chao; Li, Jiayu; Chen, Xiaoxia; Gao, Guanghui; Li, Wei; Zhou, Fei; Zhou, Caicun

2013-08-01

Epidermal growth factor receptor (EGFR) activating mutation is an important predictive biomarker of EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC), while family history of cancer also plays an important role in the neoplasia of lung cancer. This study aimed to investigate the association between family history of cancer and EGFR mutation status in NSCLC population. From February 2008 to May 2012, 538 consecutive NSCLC patients with known EGFR mutation status were included into this study. Amplification refractory mutation system (ARMS) method was used to detect EGFR mutation. The associations between EGFR mutation and family history of cancer were evaluated using logistic regression models. EGFR activating mutation was found in 220 patients and 117 patients had family cancer histories among first-degree relatives. EGFR mutation was more frequently detected in adenocarcinoma patients (p < 0.001), never-smoker (p < 0.001) and with family history of cancer (p = 0.031), especially who had family history of lung cancer (p = 0.008). In multivariate analysis, the association of EGFR mutation with family history of cancer also existed (p = 0.027). NSCLC patients with family history of cancer, especially family history of lung cancer, might have a significantly higher incidence of EGFR activating mutation. Crown Copyright © 2013. Published by Elsevier Ireland Ltd. All rights reserved.

CEP250 mutations associated with mild cone-rod dystrophy and sensorineural hearing loss in a Japanese family.

PubMed

Kubota, Daiki; Gocho, Kiyoko; Kikuchi, Sachiko; Akeo, Keiichiro; Miura, Masahiro; Yamaki, Kunihiko; Takahashi, Hiroshi; Kameya, Shuhei

2018-05-02

CEP250 encodes the C-Nap1 protein which belongs to the CEP family of proteins. C-Nap1 has been reported to be expressed in the photoreceptor cilia and is known to interact with other ciliary proteins. Mutations of CEP250 cause atypical Usher syndrome which is characterized by early-onset sensorineural hearing loss (SNHL) and a relatively mild retinitis pigmentosa. This study tested the hypothesis that the mild cone-rod dystrophy (CRD) and SNHL in a non-consanguineous Japanese family was caused by CEP250 mutations. Detailed ophthalmic and auditory examinations were performed on the proband and her family members. Whole exome sequencing (WES) was used on the DNA obtained from the proband. Electrophysiological analysis revealed a mild CRD in two family members. Adaptive optics (AO) imaging showed reduced cone density around the fovea. Auditory examinations showed a slight SNHL in both patients. WES of the proband identified compound heterozygous variants c.361C>T, p.R121*, and c.562C>T, p.R188* in CEP250. The variants were found to co-segregate with the disease in five members of the family. The variants of CEP250 are both null variants and according to American College of Medical Genetics and Genomics (ACMG) standards and guideline, these variants are classified into the very strong category (PVS1). The criteria for both alleles will be pathogenic. Our data indicate that mutations of CEP250 can cause mild CRD and SNHL in Japanese patients. Because the ophthalmological phenotypes were very mild, high-resolution retinal imaging analysis, such as AO, will be helpful in diagnosing CEP250-associated disease.

A homozygous CARD9 mutation in a family with susceptibility to fungal infections.

PubMed

Glocker, Erik-Oliver; Hennigs, Andre; Nabavi, Mohammad; Schäffer, Alejandro A; Woellner, Cristina; Salzer, Ulrich; Pfeifer, Dietmar; Veelken, Hendrik; Warnatz, Klaus; Tahami, Fariba; Jamal, Sarah; Manguiat, Annabelle; Rezaei, Nima; Amirzargar, Ali Akbar; Plebani, Alessandro; Hannesschläger, Nicole; Gross, Olaf; Ruland, Jürgen; Grimbacher, Bodo

2009-10-29

Chronic mucocutaneous candidiasis may be manifested as a primary immunodeficiency characterized by persistent or recurrent infections of the mucosa or the skin with candida species. Most cases are sporadic, but both autosomal dominant inheritance and autosomal recessive inheritance have been described. We performed genetic studies in 36 members of a large, consanguineous five-generation family, in which 4 members had recurrent fungal infections and an additional 3 members died during adolescence, 2 after invasive infection of the brain with candida species. All 36 family members were enrolled in the study, and 22 had blood samples taken for DNA analysis. Homozygosity mapping was used to locate the mutated gene. In the 4 affected family members (patients) and the 18 unaffected members we sequenced CARD9, the gene encoding the caspase recruitment domain-containing protein 9, carried out T-cell phenotyping, and performed functional studies, with the use of either leukocytes from the patients or a reconstituted murine model of the genetic defect. We found linkage (lod score, 3.6) to a genomic interval on chromosome 9q, including CARD9. All four patients had a homozygous point mutation in CARD9, resulting in a premature termination codon (Q295X). Healthy family members had wild-type expression of the CARD9 protein; the four patients lacked wild-type expression, which was associated with low numbers of Th17 cells (helper T cells producing interleukin-17). Functional studies based on genetic reconstitution of myeloid cells from Card9(-/-) mice showed that the Q295X mutation impairs innate signaling from the antifungal pattern-recognition receptor dectin-1. An autosomal recessive form of susceptibility to chronic mucocutaneous candidiasis is associated with homozygous mutations in CARD9. 2009 Massachusetts Medical Society

Family environment of bipolar families: a UK study.

PubMed

Barron, Evelyn; Sharma, Aditya; Le Couteur, James; Rushton, Stephen; Close, Andrew; Kelly, Thomas; Grunze, Heinz; Nicol Ferrier, Ian; Le Couteur, Ann

2014-01-01

Aspects of family environment (FE) such as family support, organisational structure and levels of conflict can increase risk of Bipolar Disorder (BD) in offspring of BD parents. The family environment of 16 BD and 23 healthy control (HC) families was assessed using the Family Environment Scale (FES). Canonical Correspondence Analysis (CCA) was used to determine the degree of variation in scores on the FES dimensions within each family and a Generalised Linear Modelling (GLM) approach was used to investigate the extent to which scores on the different FES dimensions differed between families. On the FES, BD families experienced an environment with higher levels of conflict and lower levels of expressiveness, organisation, intellectual-cultural orientation and active-recreational orientation than healthy control families. Differences in FES scores were driven by presence of parental BD and total number of children in the family. However, socio-economic status (SES) was not found to have an effect in this study. As an American instrument the FES may not have been sensitive enough to the cultural context of a UK sample. The relatively small sample size used may have limited the statistical power of the study. Greater numbers of children have the same effect on levels of conflict as the presence of BD, while SES does not appear to be as important a factor in FE as previously thought. Our results suggest that family based interventions focusing on psychoeducation and improved communication within these families may address issues of conflict, organisation and expressiveness. Crown Copyright © 2013 Published by Elsevier B.V. All rights reserved.

Solo and Small Practices: A Vital, Diverse Part of Primary Care.

PubMed

Liaw, Winston R; Jetty, Anuradha; Petterson, Stephen M; Peterson, Lars E; Bazemore, Andrew W

2016-01-01

Solo and small practices are facing growing pressure to consolidate. Our objectives were to determine (1) the percentage of family physicians in solo and small practices, and (2) the characteristics of and services provided by these practices. A total of 10,888 family physicians seeking certification through the American Board of Family Medicine in 2013 completed a demographic survey. Their practices were split into categories by size: solo, small (2 to 5 providers), medium (6 to 20 providers), and large (more than 20 providers). We also determined the rurality of the county where the physicians practiced. We developed 2 logistic regression models: one assessed predictors of practicing in a solo or small practice, while the other was restricted to solo and small practices and assessed predictors of practicing in a solo practice. More than one-half of respondents worked in solo or small practices. Small practices were the largest group (36%) and were the most likely to be located in a rural setting (20%). The likelihood of having a care coordinator and medical home certification increased with practice size. Physicians were more likely to be practicing in small or solo practices (vs medium-sized or large ones) if they were African American or Hispanic, had been working for more than 30 years, and worked in rural areas. Physicians were more likely to be practicing in small practices (vs solo ones) if they worked in highly rural areas. Family physicians in solo and small practices comprised the majority among all family physicians seeking board certification and were more likely to work in rural geographies. Extension programs and community health teams have the potential to support transformation within these practices. © 2016 Annals of Family Medicine, Inc.

Not Your Family Farm

ERIC Educational Resources Information Center

Tenopir, Carol; Baker, Gayle; Grogg, Jill E.

2007-01-01

The information industry continues to consolidate, just as agribusiness has consolidated and now dominates farming. Both the family farm and the small information company still exist but are becoming rarer in an age of mergers, acquisitions, and increased economies of scale. Small companies distinguish themselves by high quality, special themes,…

Interpretations of family size distributions: The Datura example

NASA Astrophysics Data System (ADS)

Henych, Tomáš; Holsapple, Keith A.

2018-04-01

Young asteroid families are unique sources of information about fragmentation physics and the structure of their parent bodies, since their physical properties have not changed much since their birth. Families have different properties such as age, size, taxonomy, collision severity and others, and understanding the effect of those properties on our observations of the size-frequency distribution (SFD) of family fragments can give us important insights into the hypervelocity collision processes at scales we cannot achieve in our laboratories. Here we take as an example the very young Datura family, with a small 8-km parent body, and compare its size distribution to other families, with both large and small parent bodies, and created by both catastrophic and cratering formation events. We conclude that most likely explanation for the shallower size distribution compared to larger families is a more pronounced observational bias because of its small size. Its size distribution is perfectly normal when its parent body size is taken into account. We also discuss some other possibilities. In addition, we study another common feature: an offset or "bump" in the distribution occurring for a few of the larger elements. We hypothesize that it can be explained by a newly described regime of cratering, "spall cratering", which controls the majority of impact craters on the surface of small asteroids like Datura.

Analysis of MYO7A in a Moroccan family with Usher syndrome type 1B: novel loss-of-function mutation and non-pathogenicity of p.Y1719C.

PubMed

Boulouiz, Redouane; Li, Yun; Abidi, Omar; Bolz, Hanno; Chafik, Abdelaziz; Kubisch, Christian; Roub, Hassan; Wollnik, Bernd; Barakat, Abdelhamid

2007-10-02

Mutations in the MYO7A gene are responsible for Usher syndrome type 1B (USH1B), the most common USH1 subtype, which accounts for the largest proportion of USH1 cases in most populations. Molecular genetic diagnosis in Usher syndrome is well established and identification of the underlying mutations in Usher patients is important for confirmation of the clinical diagnosis and genetic counseling. We analyzed a large consanguineous USH1 family from Morocco and linked the disease in this family to the MYO7A/USH1B locus. We identified the frequently described missense change p.Y1719C. In addition, we found the homozygous c.1687G>A mutation in the last nucleotide of exon 14, which is predicted to result in aberrant splicing and may lead to loss of MYO7A transcript. We further showed that p.Y1719C is not disease-causing but does represent a frequent polymorphism in the Moroccan population, with an estimated carrier frequency of 0.07. This finding has an important impact for molecular diagnosis and genetic counseling in USH1B families.

Mutation analysis of COL4A3 and COL4A4 genes in a Chinese autosomal-dominant Alport syndrome family.

PubMed

Guo, Liwei; Li, Duan; Dong, Shuangshuang; Wan, Donghao; Yang, Baosheng; Huang, Yanmei

2017-06-01

Autosomal dominant Alport syndrome (ADAS) accounts for 5% of all cases of Alport syndrome (AS), a primary basement membrane disorder arising from mutations in genes encoding the type IV collagen protein family.Mutations in COL4A3 and COL4A4 genes were reported to be associated with ADAS. In this study, clinical data in a large consanguineous family with seven affected members were reviewed, and genomic DNA was extracted. For mutation screening, all exons of COL4A3 and COL4A4 genes were polymerase chain reaction-amplified and direct sequenced from genomic DNA, and the mutations were analyzed by comparing with members in this family, 100 ethnicitymatched controls and the sequence of COL4A3 and COL4A4 genes from GenBank. A novel mutation determining a nucleotide change was found, i.e. c.4195 A>T (p.Met1399Leu) at 44th exon of COL4A4 gene, and this mutation showed heterozygous in all patients of this family. Also a novel intron mutation (c.4127+11 C>T) was observed at COL4A4 gene. Thus the novel missense mutation c.4195 A>T (p.Met1399Leu) and the intron mutation (c.4127+11 C>T) at COL4A4 gene might be responsible for ADAS of this family. Our results broadened the spectrum of mutations in COL4A4 and had important implications in the diagnosis, prognosis, and genetic counselling of ADAS.

[Experience in molecular diagnostic in hereditary neuropathies in a pediatric tertiary hospital].

PubMed

Fernández-Ramos, Joaquín A; López-Laso, Eduardo; Camino-León, Rafael; Gascón-Jiménez, Francisco J; Jiménez-González, M Dolores

2015-12-01

Charcot-Marie-Tooth (CMT) is the most common hereditary sensory motor neuropathy. Advances in molecular diagnosis have increased the diagnostic possibilities of these patients. Retrospective study of 36 pediatric patients diagnosed with CMT in a tertiary center in 2003-2015. We found 16 patients were diagnosed by a duplication in PMP22; two cases were diagnosed of hereditary neuropathy with liability to pressure palsies, one with a point mutation in PMP22; a male with a mild demyelinating phenotype, without family history, was diagnosed with GJB1 mutation; in a patient with a peripheral hypotonia at birth and axonal pattern in EMG by mutation in MFN2; a gypsy patient, with consanguineous family, CMT4D, was identified by a mutation in the gene NDRG1; a patient with multiplex congenital arthrogryposis and vocal cord paralysis, whose mother had a scapular-peroneal syndrome, had a congenital spinal muscular atrophy with mild distal axonal neuropathy by mutation in gene TRPV4; three girls, from a gypsy consanguineous family, with axonal CMT with neuromyotonic discharges were diagnosed by a mutation in the gene HINT1; twelve patients haven't molecular diagnosis currently. CMT1A predominated in our series (44%), as previous studies. We emphasize the description of a patient with a mutation in TRPV4 recently described as a cause of CMT2C and three cases, of gypsy consanguineous family, with the same mutation in HINT1 gene, recently described as a cause of axonal neuropathy with neuromyotonia, autosomal recessive (AR-CMT2). The proportion of patients without molecular diagnosis is similar to main European series.

Pathogenic Variants in PIGG Cause Intellectual Disability with Seizures and Hypotonia

PubMed Central

Makrythanasis, Periklis; Kato, Mitsuhiro; Zaki, Maha S.; Saitsu, Hirotomo; Nakamura, Kazuyuki; Santoni, Federico A.; Miyatake, Satoko; Nakashima, Mitsuko; Issa, Mahmoud Y.; Guipponi, Michel; Letourneau, Audrey; Logan, Clare V.; Roberts, Nicola; Parry, David A.; Johnson, Colin A.; Matsumoto, Naomichi; Hamamy, Hanan; Sheridan, Eamonn; Kinoshita, Taroh; Antonarakis, Stylianos E.; Murakami, Yoshiko

2016-01-01

Glycosylphosphatidylinositol (GPI) is a glycolipid that anchors >150 various proteins to the cell surface. At least 27 genes are involved in biosynthesis and transport of GPI-anchored proteins (GPI-APs). To date, mutations in 13 of these genes are known to cause inherited GPI deficiencies (IGDs), and all are inherited as recessive traits. IGDs mainly manifest as intellectual disability, epilepsy, coarse facial features, and multiple organ anomalies. These symptoms are caused by the decreased surface expression of GPI-APs or by structural abnormalities of GPI. Here, we present five affected individuals (from two consanguineous families from Egypt and Pakistan and one non-consanguineous family from Japan) who show intellectual disability, hypotonia, and early-onset seizures. We identified pathogenic variants in PIGG, a gene in the GPI pathway. In the consanguineous families, homozygous variants c.928C>T (p.Gln310∗) and c.2261+1G>C were found, whereas the Japanese individual was compound heterozygous for c.2005C>T (p.Arg669Cys) and a 2.4 Mb deletion involving PIGG. PIGG is the enzyme that modifies the second mannose with ethanolamine phosphate, which is removed soon after GPI is attached to the protein. Physiological significance of this transient modification has been unclear. Using B lymphoblasts from affected individuals of the Egyptian and Japanese families, we revealed that PIGG activity was almost completely abolished; however, the GPI-APs had normal surface levels and normal structure, indicating that the pathogenesis of PIGG deficiency is not yet fully understood. The discovery of pathogenic variants in PIGG expands the spectrum of IGDs and further enhances our understanding of this etiopathogenic class of intellectual disability. PMID:26996948

Homozygous single base deletion in TUSC3 causes intellectual disability with developmental delay in an Omani family.

PubMed

Al-Amri, Ahmed; Saegh, Abeer Al; Al-Mamari, Watfa; El-Asrag, Mohammed E; Ivorra, Jose L; Cardno, Alastair G; Inglehearn, Chris F; Clapcote, Steven J; Ali, Manir

2016-07-01

Intellectual disability (ID) is the term used to describe a diverse group of neurological conditions with congenital or juvenile onset, characterized by an IQ score of less than 70 and difficulties associated with limitations in cognitive function and adaptive behavior. The condition can be inherited or caused by environmental factors. The genetic forms are heterogeneous, with mutations in over 500 known genes shown to cause the disorder. We report a consanguineous Omani family in which multiple individuals have ID and developmental delay together with some variably present features including short stature, microcephaly, moderate facial dysmorphism, and congenital malformations of the toes or hands. Homozygosity mapping combined with whole exome next generation sequencing identified a novel homozygous single base pair deletion in TUSC3, c.222delA, p.R74 fs. The mutation segregates with the disease phenotype in a recessive manner and is absent in 60,706 unrelated individuals from various disease-specific and population genetic studies. TUSC3 mutations have been previously identified as causing either syndromic or non-syndromic ID in patients from France, Italy, Iran and Pakistan. This paper supports the previous clinical descriptions of the condition caused by TUSC3 mutations and describes the seventh family with mutations in this gene, thus contributing to the genetic spectrum of mutations. This is the first report of a family from the Arabian peninsula with this form of ID. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Family Child Care Licensing Study, 2002.

ERIC Educational Resources Information Center

Children's Foundation, Washington, DC.

This report presents the findings of the 2002 national survey of state child care regulatory agencies to update and expand family child care regulatory information published in the 2001 study. Data on small family child care homes and group or large family child care homes are organized into the following 23 categories: (1) number of regulated…

Family Child Care Licensing Study, 2001.

ERIC Educational Resources Information Center

Children's Foundation, Washington, DC.

This report presents the findings of the 2001 national survey of state child care regulatory agencies to update and expand family child care regulatory information published in the 2000 study. Data on small family child care homes and group or large family child care homes are organized into the following 23 categories: (1) number of regulated…

Family Child Care Licensing Study, 2000.

ERIC Educational Resources Information Center

Kelly, Nia, Comp.

This report presents the findings of the 2000 national survey of state child care regulatory agencies to update and expand family child care regulatory information published in the 1999 study. Data on small family child care homes and group or large family child care homes are organized in 23 categories: (1) number of regulated homes; (2)…

Family Child Care Licensing Study, 2003.

ERIC Educational Resources Information Center

Hollestelle, Kay; Koch, Pauline D.

This report presents the findings of the 2003 national survey of state child care regulatory agencies to update and expand family child care regulatory information published in the 2002 study. Data on small family child care homes and group or large family child care homes are organized into the following 23 categories: (1) number of regulated…

Isolated familial somatotropinomas: clinical features and analysis of the MEN1 gene.

PubMed

De Menis, Ernesto; Prezant, Toni R

2002-01-01

Isolated familial somatotropinomas (IFS) rarely occurs in the absence of multiple endocrine neoplasia type I (MEN1) or the Carney complex. In the present study we report two Italian siblings affected by GH-secreting adenomas. There was no history of parental consanguinity. The sister presented at 18 years of age with secondary amenorrhea and acromegalic features and one of her two brothers presented with gigantism at the same age. Endocrinological investigations confirmed GH hypersecretion in both cases. Although a pituitary microadenoma was detected in both patients, transsphenoidal surgery was not successful. The sister received conventional radiotherapy and acromegaly is now considered controlled; the brother is being treated with octreotide LAR 30 mg monthly and the disease is considered clinically active. Patients, their parents and the unaffected brother underwent extensive evaluation, and no features of MEN1 or Carney complex were found. Analysis of polymorphic microsatellite markers from chromosome 11q13 (D11S599, D11S4945, D11S4939, D11S4938 and D11S987) showed that the acromegalic siblings had inherited different maternal chromosomes and shared the paternal chromosome. No pathogenic MEN1 sequence changes were detected by sequencing or dideoxy fingerprinting of the coding sequence (exons 2-10) and exon/intron junctions. Although mutations in the promoter, introns or untranslated regions of the MEN1 gene cannot be excluded, germline mutations within the coding region of this gene do not appear responsible for IFS in this family.

Hereditary motor and sensory neuropathy Lom type in a Serbian family.

PubMed

Dacković, J; Keckarević-Marković, M; Komazec, Z; Rakocević-Stojanović, V; Lavrnić, D; Stević, Z; Ribarić, K; Romac, S; Apostolski, S

2008-10-01

Hereditary motor and sensory neuropathy Lom type (HMSNL), also called CMT 4D, a hereditary autosomal recessive neuropathy, caused by mutation in N-Myc downstream regulated gene 1 (NDRG1 gene), was first described in a Bulgarian Gypsy population near Lom and later has been found in Gypsy communities in Italy, Spain, Slovenia and Hungary. We present two siblings with HMSNL, female and male, aged 30 and 26, respectively in a Serbian non-consanguineous family of Gypsy ethnic origin. They had normal developmental milestones. Both had symptoms of lower limb muscle weakness and walking difficulties with frequent falls, which began at the age of seven. At the age of 12, they developed hearing problems and at the age of 15 hand muscle weakness. Neurological examination revealed sensorineural hearing loss, dysarthria, severe distal and mild proximal muscle wasting and weakness, areflexia and impairment of all sensory modalities of distal distribution. Electrophysiological study revealed denervation with severe and early axonal loss. Sensorineural hearing loss was confirmed on electrocochleography and brainstem evoked potentials. Molecular genetic testing confirmed homozygote C564t (R148X) mutation in NDRG1 gene.

The validity and reliability of the Finnish Family Empowerment Scale (FES): a survey of parents with small children.

PubMed

Vuorenmaa, M; Halme, N; Åstedt-Kurki, P; Kaunonen, M; Perälä, M-L

2014-07-01

The Family Empowerment Scale (FES) is a widely used instrument which measures the parents' own sense of their empowerment at the level of the family, service system and community. It was originally developed for parents of children with emotional disabilities. The aims of this study were to evaluate the validity and reliability of the Finnish FES and to examine its responsiveness in measuring the empowerment of parents with small children. The English FES was translated into Finnish using back translation and modified so as to be generic and convenient for all families. The construct, convergent, discriminant and concurrent validities, reliability and responsiveness of the Finnish FES were examined. Participants (n = 955) were the parents of children aged 0-9 years who had been selected using stratified random sampling. Confirmatory factor analysis proved that the Finnish FES had three subscales based on the original FES. Convergent and discriminant validities confirmed and supported the same construct. The relationship between parents' participation and empowerment was tested for concurrent validity. As in previous FES studies, the participating parents were more empowered, which supported the concurrent validity. The reliability of the Finnish FES proved acceptable for both parents. The Finnish FES could also discriminate the responses of the parents. Participation in the activities organized by the family service system influenced parents' perceptions of empowerment more than did their background characteristics. The Finnish FES is a valid and reliable instrument and it is suitable for measuring the empowerment of parents. However, it is necessary to consider how the FES would identify in the best way the parents who perhaps need some help. © 2013 John Wiley & Sons Ltd.

Asteroid families - An initial search

NASA Technical Reports Server (NTRS)

Williams, James G.

1992-01-01

A stereo examination was conducted for clusters in three-dimensional proper element space within a sample of both numbered and faint Palomar-Leiden Survey (PLS) asteroids. The clusters were then objectively filtered for small Poisson probability of chance occurrence; 104 were accepted as families with 4- to 12-member populations, and are interpreted as impact-generated. Structure is common in the well-populated families: the better-sampled families are accordingly discussed in terms of their geometry and taxonomy. Some families are very rich in faint PLS members.

Respiratory Protection Behavior and Respiratory Indices among Poultry House Workers on Small, Family-Owned Farms in North Carolina: A Pilot Project.

PubMed

Kearney, Gregory D; Gallagher, Barbara; Shaw, Robert

2016-01-01

The aim of this pilot study was to evaluate respiratory behavior and respiratory indices of poultry workers on family-owned, poultry farms with 10 or less employees in North Carolina. A field study was conducted to collect data on participants (N = 24) using spirometry, fractional exhaled nitric oxide (Feno), and an interviewer-administered questionnaire. The majority of workers (76%) ranked respiratory protection as being important, yet 48% reported never or rarely wearing respiratory protection when working in dusty conditions. A large percent of workers reported eye (55%) and nasal (50%) irritation and dry cough (50%). On average, pulmonary lung function and Feno tests were normal among nonsmokers. In bivariate analysis, significant associations were identified between working 7 days on the farm (P = .01), with eye irritation, and working 5 or fewer years in poultry farming (P = .01). Poultry workers on family-owned farms spend a considerable amount of work time in poultry houses and report acute respiratory-related health symptoms. Administrative controls among small, family-owned poultry farms are necessary to improve and promote safety and health to its employees.

Calling-in the Family: Dialogic Performances of Family Conflict

ERIC Educational Resources Information Center

Congdon, Mark, Jr.; Herakova, Liliana; Bishop, Jessica

2018-01-01

Courses: Introduction to Communication, Introduction to Interpersonal Communication, Family Communication, Small Group Communication, Communication and Listening. Objectives: By this end of this activity, students will be able to identify and practice supportive and defensive communication; understand a dialogic approach to conflict; and…

A Dark Asteroid Family in the Phocaea Region

NASA Astrophysics Data System (ADS)

Novaković, Bojan; Tsirvoulis, Georgios; Granvik, Mikael; Todović, Ana

2017-06-01

We report the discovery of a new asteroid family among the dark asteroids residing in the Phocaea region the Tamara family. We make use of available physical data to separate asteroids in the region according to their surface reflectance properties, and establish the membership of the family. We determine the slope of the cumulative magnitude distribution of the family, and find it to be significantly steeper than the corresponding slope of all the asteroids in the Phocaea region. This implies that subkilometer dark Phocaeas are comparable in number to bright S-type objects, shedding light on an entirely new aspect of the composition of small Phocaea asteroids. We then use the Yarkovsky V-shape based method and estimate the age of the family to be 264 ± 43 Myr. Finally, we carry out numerical simulations of the dynamical evolution of the Tamara family. The results suggest that up to 50 Tamara members with absolute magnitude H< 19.4 may currently be found in the near-Earth region. Despite their relatively small number in the near-Earth space, the rate of Earth impacts by small, dark Phocaeas is non-negligible.

A novel mutation in homeobox DNA binding domain of HOXC13 gene underlies pure hair and nail ectodermal dysplasia (ECTD9) in a Pakistani family.

PubMed

Khan, Anwar Kamal; Muhammad, Noor; Aziz, Abdul; Khan, Sher Alam; Shah, Khadim; Nasir, Abdul; Khan, Muzammil Ahmad; Khan, Saadullah

2017-04-12

Pure hair and nail ectodermal dysplasia (PHNED) is a congenital disorder of hair abnormalities and nail dysplasia. Both autosomal recessive and dominant inheritance fashion of PHNED occurs. In literature, to date, five different forms of PHNED have been reported at molecular level, having three genes known and two loci with no gene yet. In this study, a four generations consanguineous family of Pakistani origin with autosomal recessive PHNED was investigated. Affected members exhibited PHNED phenotypes with involvement of complete hair loss and nail dysplasia. To screen for mutation in the genes (HOXC13, KRT74, KRT85), its coding exons and exons-intron boundaries were sequenced. The 3D models of normal and mutated HOXC13 were predicted by using homology modeling. Through investigating the family to known loci, the family was mapped to ectodermal dysplasia 9 (ECTD9) loci with genetic address of 12q13.13. Mutation screening revealed a novel missense mutation (c.929A > C; p.Asn310Thr) in homeobox DNA binding domain of HOXC13 gene in affected members of the family. Due to mutation, loss of hydrogen bonding and difference in potential energy occurs, which may resulting in alteration of protein function. This is the first mutation reported in homeodomain, while 5 th mutation reported in HOXC13 gene causing PHNED.

Prevalence and risk factors for neurological disorders in children aged 6 months to 2 years in northern India.

PubMed

Kumar, Rashmi; Bhave, Anupama; Bhargava, Roli; Agarwal, Girdhar G

2013-04-01

To study prevalence and risk factors for neurological disorders--epilepsy, global developmental delay, and motor, vision, and hearing defects--in children aged 6 months to 2 years in northern India. A two-stage community survey for neurological disorders was conducted in rural and urban areas of Lucknow. After initial screening with a new instrument, the Lucknow Neurodevelopment Screen, screen positives and a random proportion of screen negatives were validated using predefined criteria. Prevalence was calculated by weighted estimates. Demographic, socio-economic, and medical risk factors were compared between validated children who were positive and negative for neurological disorders by univariate and logistic regression analysis. Of 4801 children screened (mean age [SD] 15.32mo [5.96]; 2542 males, 2259 females), 196 were positive; 190 screen positives and 269 screen negatives were validated. Prevalence of neurological disorders was 27.92 per 1000 (weighted 95% confidence interval 12.24-43.60). Significant risk factors (p≤0.01) for neurological disorders were higher age in months (p=0.010), lower mean number of appliances in the household (p=0.001), consanguineous marriage of parents (p=0.010), family history of neurological disorder (p=0.001), and infants born exceptionally small (parental description; p=0.009). On logistic regression, the final model included age (p=0.0193), number of appliances (p=0.0161), delayed cry at birth (p=0.0270), postneonatal meningoencephalitis (p=0.0549), and consanguinity (p=0.0801). Perinatal factors, lower socio-economic status, and consanguinity emerged as predictors of neurological disorders. These factors are largely modifiable. © The Authors. Developmental Medicine & Child Neurology © 2013 Mac Keith Press.

Studying p53 family proteins in yeast: Induction of autophagic cell death and modulation by interactors and small molecules

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leão, Mariana; Gomes, Sara; Bessa, Cláudia

In this work, the yeast Saccharomyces cerevisiae was used to individually study human p53, p63 (full length and truncated forms) and p73. Using this cell system, the effect of these proteins on cell proliferation and death, and the influence of MDM2 and MDMX on their activities were analyzed. When expressed in yeast, wild-type p53, TAp63, ΔNp63 and TAp73 induced growth inhibition associated with S-phase cell cycle arrest. This growth inhibition was accompanied by reactive oxygen species production and autophagic cell death. Furthermore, they stimulated rapamycin-induced autophagy. On the contrary, none of the tested p53 family members induced apoptosis either permore » se or after apoptotic stimuli. As previously reported for p53, also TAp63, ΔNp63 and TAp73 increased actin expression levels and its depolarization, suggesting that ACT1 is also a p63 and p73 putative yeast target gene. Additionally, MDM2 and MDMX inhibited the activity of all tested p53 family members in yeast, although the effect was weaker on TAp63. Moreover, Nutlin-3a and SJ-172550 were identified as potential inhibitors of the p73 interaction with MDM2 and MDMX, respectively. Altogether, the yeast-based assays herein developed can be envisaged as a simplified cell system to study the involvement of p53 family members in autophagy, the modulation of their activities by specific interactors (MDM2 and MDMX), and the potential of new small molecules to modulate these interactions. - Highlights: • p53, p63 and p73 are individually studied in the yeast S. cerevisiae. • p53 family members induce ROS production, cell cycle arrest and autophagy in yeast. • p53 family members increase actin depolarization and expression levels in yeast. • MDM2 and MDMX inhibit the activity of p53 family members in yeast. • Yeast can be a useful tool to study the biology and drugability of p53, p63 and p73.« less

Small Family, Smart Family? Family Size and the IQ Scores of Young Men. NBER Working Paper No. 13336

ERIC Educational Resources Information Center

Black, Sandra E.; Devereux, Paul J.; Salvanes, Kjell G.

2007-01-01

How do families influence the ability of children? Cognitive skills have been shown to be a strong predictor of educational attainment and future labor market success; as a result, understanding the determinants of cognitive skills can lead to a better understanding of children's long run outcomes. This paper uses a large dataset on the male…

Which family--what therapy: Maori culture, families and family therapy in New Zealand.

PubMed

Kumar, Shailesh; Dean, Peter; Smith, Barry; Mellsop, Graham W

2012-04-01

New Zealand is a relatively young and small country which has seen steady migration for nearly seven centuries. Despite a long history of rivalry and hostility between Maori and European values, the country has also seen some significant synergism between the two cultures. For the last three decades Asians have also migrated at a significant pace. The country faces the challenge of delivering quality mental health services to such cultures which are bifurcated in being socio-centric (Maori, Pacific Islanders and Asian total 32% combined) or ego-centric (European total 68%). Significant progress has been made in including families of the mentally ill in their treatment and care planning. Legislative requirements have been introduced for the family to be consulted in the treatment of those who are being compelled to receive psychiatric care under the Mental Health Act. Models of family therapy developed through innovation meeting the unique local needs or adaptation of existing models from overseas are being used. An overview of such family therapy modalities is presented.

Socioeconomic Indicators for Small Towns. Small Town Strategy.

ERIC Educational Resources Information Center

Oregon State Univ., Corvallis. Cooperative Extension Service.

Prepared to help small towns assess community population and economic trends, this publication provides a step-by-step guide for establishing an on-going local data collection system, which is based on four local indicators and will provide accurate, up-to-date estimates of population, family income, and gross sales within a town's trade area. The…

Nonsyndromic retinitis pigmentosa is highly prevalent in the Jerusalem region with a high frequency of founder mutations.

PubMed

Sharon, Dror; Banin, Eyal

2015-01-01

Nonsyndromic retinitis pigmentosa (RP) is the most common inherited retinal degeneration, and prevalence of the disease has been reported in populations of American and European origin with a relatively low consanguinity rate. Our aim was to determine the prevalence of nonsyndromic RP in the Jerusalem region, which has a population of about 1 million individuals with a high rate of consanguinity. The patients' clinical data included eye exam findings (visual acuity, anterior segment, and funduscopy) as well as electroretinographic (ERG) testing results under scotopic and photopic conditions. Mutation analysis on a subgroup of patients was performed mainly with candidate gene analysis and homozygosity mapping. We evaluated the medical records of patients with degenerative retinal diseases residing in the Jerusalem region who were examined over the past 20 years in a large tertiary medical center. A total of 453 individuals affected with nonsyndromic RP were diagnosed at our center, according to funduscopic findings and ERG testing. Based on the estimated population size of 945,000 individuals who reside in the vicinity of Jerusalem, the prevalence of nonsyndromic RP in this region is 1:2,086. The prevalence of RP was higher among Arab Muslims (1:1,798) compared to Jews (1:2,230), mainly due to consanguineous marriages that are more common in the Arab Muslim population. To identify the genetic causes of RP in our cohort, we recruited 383 patients from 183 different families for genetic analysis: 70 with autosomal recessive (AR) inheritance, 15 with autosomal dominant, 86 isolate cases, and 12 with an X-linked inheritance pattern. In 64 (35%) of the families, we identified the genetic cause of the disease, and we revised the inheritance pattern of 20 isolate cases to the AR pattern; 49% of the families in our cohort had AR inheritance. Interestingly, in 42 (66%) of the genetically identified families, the cause of disease was a founder mutation. Previous studies

Geometrical families of mechanically stable granular packings

NASA Astrophysics Data System (ADS)

Gao, Guo-Jie; Blawzdziewicz, Jerzy; O'Hern, Corey S.

2009-12-01

We enumerate and classify nearly all of the possible mechanically stable (MS) packings of bidipserse mixtures of frictionless disks in small sheared systems. We find that MS packings form continuous geometrical families, where each family is defined by its particular network of particle contacts. We also monitor the dynamics of MS packings along geometrical families by applying quasistatic simple shear strain at zero pressure. For small numbers of particles (N<16) , we find that the dynamics is deterministic and highly contracting. That is, if the system is initialized in a MS packing at a given shear strain, it will quickly lock into a periodic orbit at subsequent shear strain, and therefore sample only a very small fraction of the possible MS packings in steady state. In studies with N>16 , we observe an increase in the period and random splittings of the trajectories caused by bifurcations in configuration space. We argue that the ratio of the splitting and contraction rates in large systems will determine the distribution of MS-packing geometrical families visited in steady state. This work is part of our long-term research program to develop a master-equation formalism to describe macroscopic slowly driven granular systems in terms of collections of small subsystems.

The Case for High Resolution Extended 6-Loci HLA Typing for Identifying Related Donors in the Indian Subcontinent.

PubMed

Agarwal, Rajat Kumar; Kumari, Ankita; Sedai, Amit; Parmar, Lalith; Dhanya, Rakesh; Faulkner, Lawrence

2017-09-01

Three-loci low-resolution (LR) or intermediate-resolution HLA typing is generally considered adequate in the related blood and marrow transplantation (BMT) context. However, a single high-resolution (HR) mismatch may have a similar adverse impact on BMT outcome as an LR one. We sought to determine the frequency of mismatches that may go undetected when standard typing (LR or 3-loci HR) is used compared with 6-loci HR typing for related donor compatibility testing, and to assess its impact on relevant BMT outcomes. We analyzed data from a total of 2554 6-loci (HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1) HR sequence-based typing (full typing [FT]) from 754 patients, 1011 siblings, and 789 parents done at DKMS Germany (www.DKMS.de) between January 1, 2014, and June 21, 2016. We also studied 38 cases in which the family had undergone 3-loci HLA typing (standard typing [ST]). Patients were from India (70%), Pakistan (22%), and Sri Lanka (8%). The IMGT/HLA database (www.ebi.ac.uk/ipd/imgt/hla) was used to tease out nonpermissive DPB1 mismatches. HLA disparity-related outcomes, such as rejection and graft-versus-host disease (GVHD) were assessed in a retrospective matched-pair cohort of 50 patients (25 with ST and 25 with FT) who underwent BMT for severe thalassemia from compatible related donors. We found fully matched (either 12/12 HR matches or with a single permissive DPB1 mismatch) related donors for 285 patients (38%). Of these donors, 89% were siblings and 11% were parents. The likelihood of matching on an individual locus on LR but not on HR was found to be 5%. A total of 9 donors (3%; 7 siblings and 2 parents) who would have been considered a full match by HR typing on A, B, and DRB1 alone were not a match by extended 6-loci HR typing. Five of these 9 donors had a mismatch on C or DQB1, and 4 had a nonpermissive DPB1 mismatch. In this group, 5 donors (56%) belonged to a consanguineous family, in 2 donors (22%) there was no reported consanguinity, and in 2 donors (22

Association of PPARγ2 gene variant Pro12Ala polymorphism with hypertension and obesity in the aboriginal Qatari population known for being consanguineous

PubMed Central

Bener, Abdulbari; Darwish, Sarah; Al-Hamaq, Abdulla OAA; Mohammad, Ramzi M; Yousafzai, Mohammad T

2013-01-01

Aim The aim of this study was to investigate the association of the Pro12Ala polymorphism of the human peroxisome proliferator-activated receptor gamma 2 (PPARγ2) gene with hypertension and obesity in a highly consanguineous aboriginal Qatari population. Design A cross-sectional survey conducted from January 2011–December 2012. Setting Primary health care clinics. Subjects A random sample of 1,528 Qatari male and female population older than 20 years of age. Materials and methods Data on age, sex, income, level of education, occupation status, body mass index, and blood pressure and lipid profile were obtained. The Pro12Ala in the PPARγ2 gene was detected on the LightCycler® using two specific probes: (Sensor [G] 5′-CTC CTA TTG ACG CAG AAA GCG-FL and PPAR Anchor 5′ LC Red 640- TCC TTC ACT GAT ACA CTG TCT GCA AAC ATA TC-PH). Univariate and multivariate logistic regression were performed. Result Out of a total 1,528 participants, 220 were diagnosed with essential hypertension, and 420 were obese. Participants with consanguinity were significantly higher among hypertensive than normotensive (41.9% versus 30.8%; P=0.001). Altogether, more than three-fourths (89%) of the participants had a wild genotype (Pro12Pro), 9.8% were heterozygous with Pro12Ala, and only 1.2% was homozygous with the Ala12Ala genotype. The frequency of the Pro allele was 94.5% in normotensive versus 90.5% in hypertensive, while the distribution of the Ala allele was 5.5% in normotensive versus 9.5% in the hypertensive group (P=0.001). The odds of hypertension were 1.7 times higher among the participants with the Ala allele as compared to those with the Pro, while adjusting for other potential confounders (adjusted odds ratio 1.69; 95% confidence interval 1.12–2.55; P=0.012). There was no association between the PPARγ2Ala allele and obesity (P=0.740). Conclusion The current study revealed an association between the PPARγ2Ala allele and hypertension in Qatar’s population. On the other

Service Family Support -- A Small-Scale Project of Educational Psychologists Working with Parents

ERIC Educational Resources Information Center

Hogg, Jane; Hart, Anne; Collins, Zoe V.

2014-01-01

Being in a Service family can be a difficult position for children and parents alike due to high levels of mobility, parental separation, and the remaining parent's stress and emotional well-being. A Service family is defined as a family with one or both parents employed by the Ministry of Defence (MOD). The current project looked at the…

Exome sequencing and SNP analysis detect novel compound heterozygosity in fatty acid hydroxylase-associated neurodegeneration

PubMed Central

Pierson, Tyler Mark; Simeonov, Dimitre R; Sincan, Murat; Adams, David A; Markello, Thomas; Golas, Gretchen; Fuentes-Fajardo, Karin; Hansen, Nancy F; Cherukuri, Praveen F; Cruz, Pedro; Blackstone, Craig; Tifft, Cynthia; Boerkoel, Cornelius F; Gahl, William A

2012-01-01

Fatty acid hydroxylase-associated neurodegeneration due to fatty acid 2-hydroxylase deficiency presents with a wide range of phenotypes including spastic paraplegia, leukodystrophy, and/or brain iron deposition. All previously described families with this disorder were consanguineous, with homozygous mutations in the probands. We describe a 10-year-old male, from a non-consanguineous family, with progressive spastic paraplegia, dystonia, ataxia, and cognitive decline associated with a sural axonal neuropathy. The use of high-throughput sequencing techniques combined with SNP array analyses revealed a novel paternally derived missense mutation and an overlapping novel maternally derived ∼28-kb genomic deletion in FA2H. This patient provides further insight into the consistent features of this disorder and expands our understanding of its phenotypic presentation. The presence of a sural nerve axonal neuropathy had not been previously associated with this disorder and so may extend the phenotype. PMID:22146942

Family Self-tailoring: Applying a Systems Approach to Improving Family Healthy Living Behaviors

PubMed Central

Moore, Shirley M.; Jones, Lenette; Alemi, Farrokh

2016-01-01

The adoption and maintenance of healthy living behaviors by individuals and families is a major challenge. We describe a new model of health behavior change, SystemCHANGE™ (SC), which focuses on the redesign of family daily routines using system improvement methods. In the SC intervention families are taught a set of skills to engage in a series of small, family self-designed experiments to test ideas to change their daily routines. The family system-oriented changes brought about by these experiments build healthy living behaviors into family daily routines so that these new behaviors happen as a matter of course, despite wavering motivation, willpower or personal effort on the part of individuals. Case stories of the use of SC to improve family healthy living behaviors are provided. Results of several pilot tests of SC indicate its potential effectiveness to change health living behaviors across numerous populations. PMID:27301950

Novel mutations in the genes TGM1 and ALOXE3 underlying autosomal recessive congenital ichthyosis

PubMed Central

Ullah, Rahim; Ansar, Muhammad; Durrani, Zaka Ullah; Lee, Kwanghyuk; Santos-Cortez, Regie Lyn P.; Muhammad, Dost; Ali, Mahboob; Zia, Muhammad; Ayub, Muhammad; Khan, Suliman; Smith, Josh D.; Nickerson, Deborah A.; Shendure, Jay; Bamshad, Michael; Leal, Suzanne M.; Ahmad, Wasim

2016-01-01

Background Ichthyoses are clinically characterized by scaling or hyperkeratosis of the skin or both. It can be an isolated condition limited to the skin or appear secondarily with involvement of other cutaneous or systemic abnormalities. Methods The present study investigated clinical and molecular characterization of three consanguineous families (A, B, C) segregating two different forms of autosomal recessive congenital ichthyosis (ARCI). Linkage in three consanguineous families (A, B, C) segregating two different forms of ARCI was searched by typing microsatellite and single nucleotide polymorphism marker analysis. Sequencing of the two genes TGM1 and ALOXE3 was performed by the dideoxy chain termination method. Results Genome-wide linkage analysis established linkage in family A to TGM1 gene on chromosome 14q11 and in families B and C to ALOXE3 gene on chromosome 17p13. Subsequently, sequencing of these genes using samples from affected family members led to the identification of three novel mutations: a missense variant p.Trp455Arg in TGM1 (family A); a nonsense variant p.Arg140* in ALOXE3 (family B); and a complex rearrangement in ALOXE3 (family C). Conclusion The present study further extends the spectrum of mutations in the two genes involved in causing ARCI. Characterizing the clinical spectrum resulting from mutations in the TGM1 and ALOXE3 genes will improve diagnosis and may direct clinical care of the family members. PMID:26578203

Development of Genetic Therapies for the Hemidesmosol Subtypes of Junction Epidermolysis Bullosa

DTIC Science & Technology

2003-11-01

Aita, V.M. and Christiano, A.M. (2001) Structural Analysis Reflects the Evolutionary Relationship between the Desmocollin Gene Family Mambers. Exp...Christiano, A.M. and Zlotogorski, A. (2003) Atrichia With Papular Lesions In Non Consanguineous Families. J. Invest. Dermatol. (in press). 36 %9 172...phenotype-genotype correlations in this disorder as well as the relationship between the skin, the musculoskeletal and the nervous systems. The Ogna Variant

Incidence, types, geographical distribution, and risk factors of congenital anomalies in Al-Ramadi Maternity and Children's Teaching Hospital, Western Iraq.

PubMed

Al-Ani, Zaid R; Al-Haj, Shaker A; Al-Ani, Muhammad M; Al-Dulaimy, Khamees M; Al-Maraie, Ayad Kh; Al-Ubaidi, Belal Kh

2012-09-01

To study the incidence, types, geographical distribution, and risk factors of congenital anomalies (CAs) in a teaching hospital. A total of 5864 neonates were examined for CAs between October 2010 and October 2011 in Al-Ramadi Maternity and Children's Teaching Hospital, Al-Ramadi, Western Iraq. Data include: neonate's name, gender, weight, and type of CAs, mother's age, residence, education, parity, consanguinity, smoking, illness, drugs, and ultrasound (U/S) results, father's age and smoking, and family recurrence of CAs. For every case, 2 controls were selected. Types and incidence of CAs was calculated. Odds ratio and confidence interval was utilized for risk factors evaluation. Overall CA incidences were 40.5/1000 for total births, 40.8/1000 live births, and 270.0/1000 for stillbirths. Twenty percent of CAs was found as multiple, 80% single, 63.8% major, and 36.2% minor. The cardiovascular system was found most affected, followed by genito-urinary system. Low birth weight, male gender, maternal smoking, consanguinity, parity, and CAs family recurrence were found to be significant risk factors, and oligohydramnios, polyhydramnios, and positive CAs by U/S, found as significant co-factors associated with CAs, while parental age, and maternal education were not considered risk factors. Although the incidence of CAs was lower than the Al-Fallujah rate, it is still higher than many developed and developing countries. Amniotic fluid volume changes in U/S may hide an ominous CA, and maternal smoking exposure during pregnancy and consanguinity may expose the family to a congenitally anomalous delivery.

Small Business Management Volume IV: Final Report. An Adult Education Program. Development, Demonstration and Evaluation of Management Education Programs for Small Business Entrepreneurs, Including Minorities.

ERIC Educational Resources Information Center

Persons, Edgar A.; Swanson, Gordon I.

The purpose of the small business management program is to help families improve the effectiveness of their business operation and enable them to reach family and business goals. Similar to a successful program in farm management education operational in Minnesota since 1952, the program includes classroom instruction, small group instruction,…

Detection of the YORP effect for small asteroids in the Karin family

NASA Astrophysics Data System (ADS)

Nesvorny, David; Carruba, Valerio; Vokrouhlicky, David

2016-10-01

The Karin family formed by a collisional breakup of a ~40-km parent asteroid only 5.75 Myr ago. The young age can be demonstrated by numerically integrating the orbits of Karin family members backward in time and showing the convergence of orbital elements. Previous work has pointed out that the convergence is not ideal if the backward integration only accounts for the gravitational perturbations from the Solar System planets. It improves when the thermal radiation force known as the Yarkovsky effect is accounted for. This method can be used to estimate the spin obliquities of Karin family members. Here we show that the obliquity distribution of diameter D=1-2 km asteroids in the Karin family is bimodal, as expected if the YORP effect acted to move obliquities toward extreme values (0 or 180 deg). The measured magnitude of the effect is consistent with the standard YORP model. Specifically, the strength of the YORP effect is inferred to be roughly 70% of the nominal YORP strength obtained for a collection of random Gaussian spheroids. The surface thermal conductivity is found to be 0.07-0.2 W/m/K (thermal inertia 300-500 in the SI units). These results are consistent with surfaces composed of rough and rocky regolith. The obliquity values predicted here for 480 members of the Karin cluster can be validated by the lightcurve inversion method. In broader context, the bimodal distribution of obliquities in the Karin cluster can be thought as an initial stage of dynamical evolution that later leads to a characteristically bi-lobed distribution of family members in the semimajor axis (e.g., Eos, Merxia or Erigone families).

Living kidney transplantation between brothers with unrecognized renal amyloidosis as the first manifestation of familial Mediterranean fever: a case report.

PubMed

Peces, Ramón; Afonso, Sara; Peces, Carlos; Nevado, Julián; Selgas, Rafael

2017-08-31

Familial Mediterranean fever is an autosomal recessive disease characterized by recurrent episodes of fever and polyserositis and by the onset of reactive amyloid-associated amyloidosis. Amyloidosis due to familial Mediterranean fever can lead to end-stage renal disease, culminating in kidney transplantation for some patients. In this study, we report the clinical outcome of two brothers with familial Mediterranean fever who were the inadvertent donor and recipient, respectively, of a kidney. Subsequently, they were diagnosed with renal amyloidosis secondary to familial Mediterranean fever and were successfully treated with anakinra and colchicine. Two brothers with familial Mediterranean fever and renal amyloidosis were the inadvertent donor and recipient, respectively, of a kidney. The recipient had presented recurrent acute febrile episodes of familial Mediterranean fever, developed nephrotic syndrome secondary to amyloidosis and needed bilateral nephrectomy and chronic dialysis. His elder brother, in apparent good health, donated his left kidney to his brother. Immediately after the kidney transplantation, both the donor and recipient presented massive proteinuria, impaired renal function and elevated serum amyloid A levels. Biopsies of the brothers' kidneys showed amyloidosis. Genetic studies thereafter revealed a homozygous variant for the MEFV gene (NM_000243.2.c.2082G > A; p.M694I) in both brothers. At this point, both the donor and recipient were treated with colchicine and anakinra, resulting in improved renal function, decreased proteinuria, undetectable serum amyloid A levels and stable renal function at 62 months of follow-up and no major adverse effects. In familial Mediterranean fever, analyses of the MEFV gene should be performed in potential live kidney donors from a direct family member (either between siblings or between parents and children). In addition, genetic studies are required when consanguinity is suspected between members involved in

Solo and Small Practices: A Vital, Diverse Part of Primary Care

PubMed Central

Liaw, Winston R.; Jetty, Anuradha; Petterson, Stephen M.; Peterson, Lars E.; Bazemore, Andrew W.

2016-01-01

PURPOSE Solo and small practices are facing growing pressure to consolidate. Our objectives were to determine (1) the percentage of family physicians in solo and small practices, and (2) the characteristics of and services provided by these practices. METHODS A total of 10,888 family physicians seeking certification through the American Board of Family Medicine in 2013 completed a demographic survey. Their practices were split into categories by size: solo, small (2 to 5 providers), medium (6 to 20 providers), and large (more than 20 providers). We also determined the rurality of the county where the physicians practiced. We developed 2 logistic regression models: one assessed predictors of practicing in a solo or small practice, while the other was restricted to solo and small practices and assessed predictors of practicing in a solo practice. RESULTS More than one-half of respondents worked in solo or small practices. Small practices were the largest group (36%) and were the most likely to be located in a rural setting (20%). The likelihood of having a care coordinator and medical home certification increased with practice size. Physicians were more likely to be practicing in small or solo practices (vs medium-sized or large ones) if they were African American or Hispanic, had been working for more than 30 years, and worked in rural areas. Physicians were more likely to be practicing in small practices (vs solo ones) if they worked in highly rural areas. CONCLUSIONS Family physicians in solo and small practices comprised the majority among all family physicians seeking board certification and were more likely to work in rural geographies. Extension programs and community health teams have the potential to support transformation within these practices. PMID:26755778

Diencephalic-Mesencephalic Junction Dysplasia: A Novel Recessive Brain Malformation

ERIC Educational Resources Information Center

Zaki, Maha S.; Saleem, Sahar N.; Dobyns, William B.; Barkovich, A. James; Bartsch, Hauke; Dale, Anders M.; Ashtari, Manzar; Akizu, Naiara; Gleeson, Joseph G.; Grijalvo-Perez, Ana Maria

2012-01-01

We describe six cases from three unrelated consanguineous Egyptian families with a novel characteristic brain malformation at the level of the diencephalic-mesencephalic junction. Brain magnetic resonance imaging demonstrated a dysplasia of the diencephalic-mesencephalic junction with a characteristic "butterfly"-like contour of the…

Smoking, alcohol and family history of cancer as risk factors for small intestinal neuroendocrine tumors: a systematic review and meta-analysis.

PubMed

Haugvik, Sven-Petter; Basim Ibrahim, Ibrahim; Hedenström, Per; Valente, Roberto; Hayes, Alastair J; Siuka, Darko; Gladhaug, Ivar Prydz; Capurso, Gabriele

2017-08-01

Risk factors for small intestinal neuroendocrine tumors (SI-NETs) are not well understood. The aim of this systematic literature review was to identify risk factors for SI-NET and to further assess these by meta-analysis. PubMed and abstracts from the ENETS and NANETS were searched for studies published until May 2015. Eligible studies were selected according to the PRISMA statement. Seven studies evaluating six individual populations were included (study accrual period 1980-2012) in the meta-analysis, involving 765 (range 17-325) cases and 502,282 (range 52-498,376) controls. All studies were case-control by design. The following risk factors were reported in ≥2 studies: family history of any cancer, family history of colorectal cancer, ever alcohol use and ever smoking. The pooled OR was 1.34 (95% CI: 1.12-1.60; p < .01; I 2  = 0.0%) for family history of any cancer, 1.43 (95% CI: 1.15-1.79; p < .01; I 2  = 0.0%) for family history of colorectal cancer, 1.04 (95% CI: 0.63-1.72; p = .87; I 2  = 65.0%) for ever alcohol use and 1.40 (95% CI: 1.06-1.86; p < .05; I 2  = 49.3%) for ever smoking. Family history of any cancer, family history of colorectal cancer and history of ever smoking were associated with an increased risk of SI-NET by meta-analysis. Alcohol consumption was not a significant risk factor for SI-NET. However, the studies reporting smoking and alcohol had a high degree of heterogeneity. Therefore, further studies are needed for clarification of smoking and alcohol as risk factors for the occurrence of SI-NET.

Mutation of KREMEN1, a modulator of Wnt signaling, is responsible for ectodermal dysplasia including oligodontia in Palestinian families.

PubMed

Issa, Yasmin A; Kamal, Lara; Rayyan, Amal Abu; Dweik, Dima; Pierce, Sarah; Lee, Ming K; King, Mary-Claire; Walsh, Tom; Kanaan, Moien

2016-10-01

Tooth development is controlled by the same processes that regulate formation of other ectodermal structures. Mutations in the genes underlying these processes may cause ectodermal dysplasia, including severe absence of primary or permanent teeth. Four consanguineous Palestinian families presented with oligodontia and hair and skin features of ectodermal dysplasia. Appearance of ectodermal dysplasia was consistent with autosomal recessive inheritance. Exome sequencing followed by genotyping of 56 informative relatives in the 4 families suggests that the phenotype is due to homozygosity for KREMEN1 p.F209S (c.626 T>C) on chromosome 22 at g.29,521,399 (hg19). The variant occurs in the highly conserved extracellular WSC domain of KREMEN1, which is known to be a high affinity receptor of Dickkopf-1, a component of the Dickkopf-Kremen-LRP6 complex, and a potent regulator of Wnt signaling. The Wnt signaling pathway is critical to development of ectodermal structures. Mutations in WNT10A, LRP6, EDA, and other genes in this pathway lead to tooth agenesis with or without other ectodermal anomalies. Our results implicate KREMEN1 for the first time in a human disorder and provide additional details on the role of the Wnt signaling in ectodermal and dental development.

Family self-tailoring: Applying a systems approach to improving family healthy living behaviors.

PubMed

Moore, Shirley M; Jones, Lenette; Alemi, Farrokh

2016-01-01

The adoption and maintenance of healthy living behaviors by individuals and families is a major challenge. We describe a new model of health behavior change, SystemCHANGE (SC), which focuses on the redesign of family daily routines using system improvement methods. In the SC intervention, families are taught a set of skills to engage in a series of small, family self-designed experiments to test ideas to change their daily routines. The family system-oriented changes brought about by these experiments build healthy living behaviors into family daily routines so that these new behaviors happen as a matter of course, despite wavering motivation, willpower, or personal effort on the part of individuals. Case stories of the use of SC to improve family healthy living behaviors are provided. Results of several pilot tests of SC indicate its potential effectiveness to change health living behaviors across numerous populations. Copyright © 2016 Elsevier Inc. All rights reserved.

[Premalignant conditions of the small bowel].

PubMed

Drastich, P

2013-01-01

Small intestinal dysplastic lesions are rare and difficult to detect before they progress to cancer. New investigative modalities, such as capsule endoscopy and doubleballoon enteroscopy, are very promising in search for premalignant lesions. Screening patients at high-risk for small bowel neoplasia is the only sensible approach. Duodenal adenoma represents the most easily accessible tumors with the possibility of curative endoscopic resection. Due to the strong association of the small bowel and colonic adenomas, it is always necessary to perform colonoscopy. In young patients, the exclusion of familial polyposis by genetic testing is always mandatory. Patients with celiac disease are especially at risk of developing nonHodgkins lymphomas and adenocarcinomas. There is a high-risk of ampuloma and other adenomas in patients with familial adenomatous polyposis. Patients with prolonged and complicated course of Crohns disease, Peutz Jeghers syndrome and patients with ileoanal pouch have higher risk of adenocarcinoma of the small intestine.

The Family Child Care Licensing Study, 1999.

ERIC Educational Resources Information Center

Children's Foundation, Washington, DC.

This report presents the findings of the 1999 national survey of state child care regulatory agencies to update and expand family child care regulatory information published in the 1998 study. Data on small family child care homes and group or large family child care homes are organized in 22 categories: (1) number of regulated homes; (2)…

Autosomal recessive spastic paraplegia (SPG30) with mild ataxia and sensory neuropathy maps to chromosome 2q37.3.

PubMed

Klebe, Stephan; Azzedine, Hamid; Durr, Alexandra; Bastien, Patrick; Bouslam, Naima; Elleuch, Nizar; Forlani, Sylvie; Charon, Celine; Koenig, Michel; Melki, Judith; Brice, Alexis; Stevanin, Giovanni

2006-06-01

The hereditary spastic paraplegias (HSPs) are a clinically and genetically heterogeneous group of neurodegenerative diseases characterized by progressive spasticity in the lower limbs. Twenty-nine different loci (SPG) have been mapped so far, and 11 responsible genes have been identified. Clinically, one distinguishes between pure and complex HSP forms which are variably associated with numerous combinations of neurological and extra-neurological signs. Less is known about autosomal recessive forms (ARHSP) since the mapped loci have been identified often in single families and account for only a small percentage of patients. We report a new ARHSP locus (SPG30) on chromosome 2q37.3 in a consanguineous family with seven unaffected and four affected members of Algerian origin living in Eastern France with a significant multipoint lod score of 3.8. Ten other families from France (n = 4), Tunisia (n = 2), Algeria (n = 3) and the Czech Republic (n = 1) were not linked to the newly identified locus thus demonstrating further genetic heterogeneity. The phenotype of the linked family consists of spastic paraparesis and peripheral neuropathy associated with slight cerebellar signs confirmed by cerebellar atrophy on one CT scan.

Pathogenic Variants in PIGG Cause Intellectual Disability with Seizures and Hypotonia.

PubMed

Makrythanasis, Periklis; Kato, Mitsuhiro; Zaki, Maha S; Saitsu, Hirotomo; Nakamura, Kazuyuki; Santoni, Federico A; Miyatake, Satoko; Nakashima, Mitsuko; Issa, Mahmoud Y; Guipponi, Michel; Letourneau, Audrey; Logan, Clare V; Roberts, Nicola; Parry, David A; Johnson, Colin A; Matsumoto, Naomichi; Hamamy, Hanan; Sheridan, Eamonn; Kinoshita, Taroh; Antonarakis, Stylianos E; Murakami, Yoshiko

2016-04-07

Glycosylphosphatidylinositol (GPI) is a glycolipid that anchors >150 various proteins to the cell surface. At least 27 genes are involved in biosynthesis and transport of GPI-anchored proteins (GPI-APs). To date, mutations in 13 of these genes are known to cause inherited GPI deficiencies (IGDs), and all are inherited as recessive traits. IGDs mainly manifest as intellectual disability, epilepsy, coarse facial features, and multiple organ anomalies. These symptoms are caused by the decreased surface expression of GPI-APs or by structural abnormalities of GPI. Here, we present five affected individuals (from two consanguineous families from Egypt and Pakistan and one non-consanguineous family from Japan) who show intellectual disability, hypotonia, and early-onset seizures. We identified pathogenic variants in PIGG, a gene in the GPI pathway. In the consanguineous families, homozygous variants c.928C>T (p.Gln310(∗)) and c.2261+1G>C were found, whereas the Japanese individual was compound heterozygous for c.2005C>T (p.Arg669Cys) and a 2.4 Mb deletion involving PIGG. PIGG is the enzyme that modifies the second mannose with ethanolamine phosphate, which is removed soon after GPI is attached to the protein. Physiological significance of this transient modification has been unclear. Using B lymphoblasts from affected individuals of the Egyptian and Japanese families, we revealed that PIGG activity was almost completely abolished; however, the GPI-APs had normal surface levels and normal structure, indicating that the pathogenesis of PIGG deficiency is not yet fully understood. The discovery of pathogenic variants in PIGG expands the spectrum of IGDs and further enhances our understanding of this etiopathogenic class of intellectual disability. Copyright © 2016 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Shodagor Family Strategies : Balancing Work and Family on the Water.

PubMed

Starkweather, Kathrine E

2017-06-01

The Shodagor of Matlab, Bangladesh, are a seminomadic community of people who live and work on small wooden boats, within the extensive system of rivers and canals that traverse the country. This unique ecology places particular constraints on family and economic life and leads to Shodagor parents employing one of four distinct strategies to balance childcare and provisioning needs. The purpose of this paper is to understand the conditions that lead a family to choose one strategy over another by testing predictions about socioecological factors that impact the sexual division of labor, including a family's stage in the domestic cycle, aspects of the local ecology, and the availability of alloparents. Results show that although each factor has an impact on the division of labor individually, a confluence of these factors best explains within-group, between-family differences in how mothers and fathers divide subsistence and childcare labor. These factors also interact in particular ways for Shodagor families, and it appears that families choose their economic strategies based on the constellation of constraints that they face. The results of these analyses have implications for theory regarding the sexual division of labor across cultures and inform how Shodagor family economic and parenting strategies should be contextualized in future studies.

A new compound heterozygous CFTR mutation in a Chinese family with cystic fibrosis.

PubMed

Xie, Yingjun; Huang, Xueqiong; Liang, Yujian; Xu, Lingling; Pei, Yuxin; Cheng, Yucai; Zhang, Lidan; Tang, Wen

2017-11-01

Cystic fibrosis (CF) is the most common autosomal recessive disease among Caucasians but is rarer in the Chinese population, because mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. To elucidate the causative role of a novel compound heterozygous mutation of CF. In this study, clinical samples were obtained from two siblings with recurrent airway infections, clubbed fingers, salt-sweat and failure to gain weight in a non-consanguineous Chinese family. Next-generation sequencing was performed on the 27 coding exons of CFTR in both children, with confirmation by Sanger sequencing. Next-generation sequencing showed the same compound heterozygous CFTR mutation (c.865A>T p.Arg289X and c.3651_3652insAAAT p.Tyr1219X) in both children. As this mutation is consistent with the clinical manifestations of CF and no other mutations were detected after scanning the gene sequence, we suggest that the CF phenotype is caused by compound heterozygosity for c.865A>T and c.3651_3652insAAAT. As c865A>T is not currently listed in the "Cystic Fibrosis Mutation Database", this information about CF in a Chinese population is of interest. © 2015 John Wiley & Sons Ltd.

Identification of a Novel Mutation in the ABCA4 Gene in a Chinese Family with Retinitis Pigmentosa Using Exome Sequencing.

PubMed

Huang, Xiangjun; Yuan, Lamei; Xu, Hongbo; Zheng, Wen; Cao, Yanna; Yi, Junhui; Guo, Yi; Yang, Zhijian; Li, Yu; Deng, Hao

2018-02-05

Retinitis pigmentosa (RP) is a group of hereditary, degenerative retinal disorders characterized by progressive retinal dysfunction, outer retina cell loss, and retinal tissue atrophy. It eventually leads to tunnel vision and legal, or total blindness. Here we aimed to reveal the causal gene and mutation contributing to the development of autosomal recessive RP (arRP) in a consanguineous family. A novel homozygous mutation, c.4845delT (p.K1616Rfs*46), in the ATP-binding cassette subfamily A member 4gene ( ABCA4 ) was identified. It may reduce ABCA4 protein activity, leading to progressive degeneration of both rod and cone photoreceptors. The study extends the arRP genotypic spectrum and confirms a genotype-phenotype relationship. This study may also disclose some new clues for RP genetic causes and pathogenesis, as well as clinical and genetic diagnosis. The research findings may contribute to improvement in clinical care, therapy, genetic screening, and counseling. ©2018 The Author(s).

Two siblings with early infantile myoclonic encephalopathy due to mutation in the gene encoding mitochondrial glutamate/H+ symporter SLC25A22.

PubMed

Cohen, Rony; Basel-Vanagaite, Lina; Goldberg-Stern, Hadassah; Halevy, Ayelet; Shuper, Avinoam; Feingold-Zadok, Michal; Behar, Doron M; Straussberg, Rachel

2014-11-01

To characterize a new subset of early myoclonic encephalopathy usually associated with metabolic etiologies with a new genetic entity. We describe two siblings with early myoclonic encephalopathy born to consanguineous parents of Arab Muslim origin from Israel. We used homozygosity mapping and candidate gene sequencing to reveal the genetic basis of the myoclonic syndrome. We found a rare missense mutation in the gene encoding one of the two mitochondrial glutamate/H symporters, SLC25A22. The phenotype of early myoclonic encephalopathy was first linked to the same mutation in 2005 in patients of the same ethnicity as our family. Owing to the devastating nature of this encephalopathy, we focus attention on its clinical history, epileptic semiology, distinct electroencephalography features, and genetic basis. We provide the evidence that an integrated diagnostic strategy combining homozygosity mapping with candidate gene sequencing is efficient in consanguineous families with highly heterogeneous autosomal recessive diseases. Copyright © 2014 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Unexpected genetic heterogeneity for primary ciliary dyskinesia in the Irish Traveller population.

PubMed

Casey, Jillian P; McGettigan, Paul A; Healy, Fiona; Hogg, Claire; Reynolds, Alison; Kennedy, Breandan N; Ennis, Sean; Slattery, Dubhfeasa; Lynch, Sally A

2015-02-01

We present a study of five children from three unrelated Irish Traveller families presenting with primary ciliary dyskinesia (PCD). As previously characterized disorders in the Irish Traveller population are caused by common homozygous mutations, we hypothesised that all three PCD families shared the same recessive mutation. However, exome sequencing showed that there was no pathogenic homozygous mutation common to all families. This finding was supported by histology, which showed that each family has a different type of ciliary defect; transposition defect (family A), nude epithelium (family B) and absence of inner and outer dynein arms (family C). Therefore, each family was analysed independently using homozygosity mapping and exome sequencing. The affected siblings in family A share a novel 1 bp duplication in RSPH4A (NM_001161664.1:c.166dup; p.Arg56Profs*11), a radial-spoke head protein involved in ciliary movement. In family B, we identified three candidate genes (CCNO, KCNN3 and CDKN1C), with a 5-bp duplication in CCNO (NM_021147.3:c.258_262dup; p.Gln88Argfs*8) being the most likely cause of ciliary aplasia. This is the first study to implicate CCNO, a DNA repair gene reported to be involved in multiciliogenesis, in PCD. In family C, we identified a ∼3.5-kb deletion in DYX1C1, a neuronal migration gene previously associated with PCD. This is the first report of a disorder in the relatively small Irish Traveller population to be caused by >1 disease gene. Our study identified at least three different PCD genes in the Irish Traveller population, highlighting that one cannot always assume genetic homogeneity, even in small consanguineous populations.

Role of DFNB1 mutations in hereditary hearing loss among assortative mating hearing impaired families from South India.

PubMed

Amritkumar, Pavithra; Jeffrey, Justin Margret; Chandru, Jayasankaran; Vanniya S, Paridhy; Kalaimathi, M; Ramakrishnan, Rajagopalan; Karthikeyen, N P; Srikumari Srisailapathy, C R

2018-06-19

DFNB1, the first locus to have been associated with deafness, has two major genes GJB2 & GJB6, whose mutations have played vital role in hearing impairment across many ethnicities in the world. In our present study we have focused on the role of these mutations in assortative mating hearing impaired families from south India. One hundred and six assortatively mating hearing impaired (HI) families of south Indian origin comprising of two subsets: 60 deaf marrying deaf (DXD) families and 46 deaf marrying normal hearing (DXN) families were recruited for this study. In the 60 DXD families, 335 members comprising of 118 HI mates, 63 other HI members and 154 normal hearing members and in the 46 DXN families, 281 members comprising of 46 HI and their 43 normal hearing partners, 50 other HI members and 142 normal hearing family members, participated in the molecular study. One hundred and sixty five (165) healthy normal hearing volunteers were recruited as controls for this study. All the participating members were screened for variants in GJB2 and GJB6 genes and the outcome of gene mutations were compared in the subsequent generation in begetting deaf offspring. The DFNB1 allele frequencies for DXD mates and their offspring were 36.98 and 38.67%, respectively and for the DXN mates and their offspring were 22.84 and 24.38%, respectively. There was a 4.6% increase in the subsequent generation in the DXD families, while a 6.75% increase in the DXN families, which demonstrates the role of assortative mating along with consanguinity in the increase of DFNB1 mutations in consecutive generations. Four novel variants, p.E42D (in GJB2 gene), p.Q57R, p.E101Q, p.R104H (in GJB6 gene) were also identified in this study. This is the first study from an Indian subcontinent reporting novel variants in the coding region of GJB6 gene. This is perhaps the first study in the world to test real-time, the hypothesis proposed by Nance et al. in 2000 (intense phenotypic assortative mating

Fertility and its relationship with sociocultural factors in Kuwaiti society.

PubMed

Al-Kandari, Y Y

2007-01-01

The aim of this study was to examine the effect of some sociocultural variables on the fertility of Kuwaiti women. A questionnaire was administered to a sample of 7749 married women (aged 15-78 years) selected randomly from 10 primary health care clinics in Kuwait. The fertility rate was 3.58 live births per woman. Fertility was higher among Sunni Muslim women, those of Bedouin ethnicity, and those in a consanguineous marriage (P < 0.001). There was a significant negative relationship between fertility and respondents' educational level, occupation, age at marriage, socioeconomic status and type of marriage (consanguineous or not). There was a positive relationship between fertility and the respondents' age and the family income.

Novel homozygous variants in ATCAY, MCOLN1, and SACS in complex neurological disorders.

PubMed

Manzoor, Humera; Brüggemann, Norbert; Hussain, Hafiz Muhammad Jafar; Bäumer, Tobias; Hinrichs, Frauke; Wajid, Muhammad; Münchau, Alexander; Naz, Sadaf; Lohmann, Katja

2018-06-01

Neurological disorders comprise a large group of clinically and genetically heterogeneous disorders, many of which have a genetic cause. In addition to a detailed neurological examination, exome sequencing is being increasingly used as a complementary diagnostic tool to identify the underlying genetic cause in patients with unclear, supposedly genetically determined disorders. To identify the genetic cause of a complex movement disorder in five consanguineous Pakistani families. We included five consanguineous Pakistani families with complex recessively inherited movement disorders. Clinical investigation including videotaping was carried out in a total of 59 family members (4-21 per family) and MRI in six patients. Exome sequencing was performed in 4-5 family members per pedigree to explore the underlying genetic cause. Patients presented a wide spectrum of neurological symptoms including ataxia and/or dystonia. We identified three novel homozygous, segregating variants in ATCAY (p.Pro200Profs*20), MCOLN1 (p.Ile184Thr), and SACS (p.Asn3040Lysfs*4) in three of the families. Thus, we were able to identify the likely cause of the disease in a considerable number of families (60%) with the relatively simple and nowadays widely available method of exome sequencing. Of note, close collaboration of neurologists and geneticists was instrumental for proper data interpretation. We expand the phenotypic, genotypic, and ethnical spectrum of mutations in these genes. Our findings alert neurologists that rare genetic causes should be considered in complex phenotypes regardless of ethnicity. Copyright © 2018 Elsevier Ltd. All rights reserved.

The role of vitamin D, obesity and physical exercise in regulation of glycemia in Type 2 Diabetes Mellitus patients.

PubMed

Bener, Abdulbari; Al-Hamaq, Abdulla O A A; Kurtulus, Eda Merve; Abdullatef, Waleed K; Zirie, Mahmoud

The aims of this study were to determine the role of vitamin D, obesity and physical exercise in the regulation of glycemia in Type 2 Diabetes Mellitus patients in a highly consanguineous population. Case and control study. The survey was carried out at the Hamad General Hospital and Primary Health Care (PHC) centers in the State of Qatar. The study was conducted from November 2012 to June 2014 among subjects above 30 years of age. Of the 2224 registered with diagnosed diabetes and free diseases attending Hamad General Hospital and PHC centers agreed and gave their consent to study. Questionnaire included socio-demographic variables, body mass index (BMI), consanguinity, lifestyle habits, family history of diabetes, blood pressure and development of diabetes complications such as retinopathy, nephropathy, and neuropathy were collected at regular intervals throughout the follow-up. Univariate and multivariate statistical analysis were performed. There were statistically significant difference between patients with diabetic and control in terms of ethnicity (p=0.012), level of education (p=0.002), occupation (p<0.001), monthly income (p<0.001), BMI(p=0.024), sport activity (p=0.018), cigarette smoking (p<0.001), consanguinity (p=0.029) and family history of Diabetes Mellitus (p<0.001) and co-morbidity hypertension (p=0.041). Further, the biochemistry values in the studied subjects with T2DM compared to healthy controls and the study revealed that serum Vitamin D, BMI, fasting glucose level, calcium, HbA1c, total cholesterol HDL, LDL, bilirubin, triglycerides, uric acid and blood pressure systolic and diastolic were higher in T2DM compared to their counterparts. Multivariate logistic regression showed that vitamin D deficiency ng/mL, Family History of T2DM, BMI (kg/m 2 ) hypertension, consanguinity, income, mother occupation, ethnicity, educational level and Lack of physical exercise variables were significant predictors of diabetes. In the group of Diabetes Mellitus

Family Child Care Licensing Study, 1998.

ERIC Educational Resources Information Center

Children's Foundation, Washington, DC.

This report details a survey of state child care regulatory agencies. Data on both small family child care homes (FCCH) and group or large family child care homes (LCCH or GCCH) are included and organized into 22 categories: (1) number of regulated homes; (2) definitions and regulatory requirements; (3) unannounced inspection procedure; (4)…

Cutaneous features associated with microcephalic osteodysplastic primordial dwarfism type II.

PubMed

Webber, Naomi; O'Toole, Edel A; Paige, David G; Rosser, Elisabeth

2008-01-01

We present an 18-month-old Pakistani girl who had short stature, craniofacial dysmorphism, and multiple café-au-lait spots. After consultation with the geneticists, microcephalic osteodysplastic primordial dwarfism type II was diagnosed (MIM210720). The presence of consanguinity in reported families is suggestive of autosomal recessive inheritance.

Identification of a novel homozygous mutation in MYO3A in a Chinese family with DFNB30 non-syndromic hearing impairment.

PubMed

Qu, Ronggui; Sang, Qing; Xu, Yao; Feng, Ruizhi; Jin, Li; He, Lin; Wang, Lei

2016-05-01

Hearing loss is a common sensory impairment. Several genetic loci or genes responsible for non-syndrome hearing loss have been identified, including the well-known deafness genes GJB2, MT-RNR1 and SLC26A4. MYO3A belongs to the myosin superfamily. Previously only three mutations in this gene have been found in an Isreali family with DFNB30, in which patients demonstrated progressive hearing loss. In this study, we characterized a consanguineous Kazakh family with congenital hearing loss. By targeted sequence capture and next-generation sequencing, we identified a homozygous mutation and did bioinformatics analysis to this mutation. A homozygous mutation, MYO3A:c.1841C>T (p.S614F), was identified to be responsible for the disease. Ser614 is located in the motor domain of MYO3A that is highly conserved among different species. Molecular modeling predicts that the conserved Ser614 may play an important role in maintaining the stability of β-sheet and the interaction between neighboring β-strand. This is the second report on MYO3A mutations in deafness and the first report in China. The finding help facilitate establishing a better relationship between MYO3A mutation and hearing phenotypes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Genetic analysis and literature review of Chinese patients with familial renal glucosuria: Identification of a novel SLC5A2 mutation.

PubMed

Wang, Xiaojing; Yu, Miao; Wang, Tong; Zhang, Huabing; Ping, Fan; Zhang, Qian; Xu, Jianping; Feng, Kai; Xiao, Xinhua

2017-06-01

Familial renal glucosuria (FRG) is an inherited renal tubular disorder characterized by persistent isolated glucosuria with normal blood glucose. SLC5A2 gene mutation was the causative of FRG. Molecular genetic analysis of SLC5A2 gene by Sanger sequencing was conducted in two unrelated non-consanguineous Chinese families with isolated glucosuria. Extensive laboratory test and physical examination were performed. In silico algorithms were used to explore the potential effect of novel mutation on SGLT2 function. We also summarized the reported SLC5A2 mutations in the Chinese patients with FRG. A novel missense mutation (c.877A>T, p.Ser293Cys) in exon 3 was detected in proband 1 with weight loss accompanying by glucosuria and in her father with normal phenotype. In family 2, a previously reported compound heterozygous mutation (c.229G>C, p.Gly77Arg; c.1540C>T, p.Pro514Ser) was identified, and her healthy parents were heterozygous mutation carriers. The p.S293C mutation was predicted to be pathogenic. No hot spot mutation was found in reported Chinese patients with FRG. The novel pathogenic SLC5A2 mutation p.S293C was responsible for the onset of FRG. Our study further confirmed the co-dominant inheritance trait with variable penetrance and expanded the clinical and genetic spectrum of FRG. Copyright © 2017 Elsevier B.V. All rights reserved.

The productivity of small animal species in small-scale mixed farming systems in subtropical Bolivia.

PubMed

Paterson, R T; Joaquín, N; Chamón, K; Palomino, E

2001-02-01

The productivity of the scavenging, small animal species (chickens, ducks, pigs, hair sheep and guinea-pigs) commonly found on small-scale farms at the forest margin in subtropical Bolivia was monitored over a full year. Chickens and guinea-pigs were kept mainly for home consumption, while ducks and pigs were kept mainly for sale. Sheep served both purposes, depending upon the family requirements. In the absence of veterinary treatment, the productivity varied greatly between farms. Pigs gave the greatest gross return, but received the largest amount of supplementary feed. Under the existing system, chickens, ducks and sheep all gave similar gross returns per breeding female, although chickens produced good returns and made a large contribution to the family diet where the reproductive efficiency was high and the chick mortality was low. Mortality resulting from disease was a major problem in poultry, while internal parasites appeared to be important limiting factors in pigs and sheep. Guinea-pigs showed no major problems apart from theft, and were an important dietary component for immigrant families from the highlands of the country. Small animal species have largely been ignored by agricultural research and development activities in Bolivia and elsewhere. They currently make significant contributions to the livelihoods of poor people in terms of both income and food security, and this could be greatly increased by simple improvements in animal husbandry.

Transfer Policies, Career, and Family: Are They Compatible?

ERIC Educational Resources Information Center

Gerstmann, Timothy K.

The effects of business transfers on families were studied through family impact analysis. A small sample (10 couples) of dual-career and dual-worker couples was utilized for the project. The sample was unusual in that both partners were employed by the same company. Four areas were examined for possible impacts of a transfer on the family: family…

Jervell and Lange-Nielsen syndrome in a father and daughter from a large highly inbred family: a 16-year follow-up of 59 living members.

PubMed

Sanyal, Shyamal Kumar; Kaul, Kanwar K; Hussein, Akhtar; Wilroy, Robert S; Agarwal, Kisan; Sohel, Saira

2013-08-01

To report the autosomal dominant inheritance of the Jervell and Lange-Nielsen syndrome in a highly inbred family, the initiation of Torsades de Pointes, and the natural history of the syndrome based on a 16-year follow-up of the kindred. A family tree was constructed that included 66 blood relatives from three successive generations. Electrocardiograms were obtained from 59 living members including the proband, four members from a nuclear family, and 54 from the extended family. Evoked response audiometry was recorded for the proband and the nuclear family. All 59 family members were followed up regularly for 16 years. A total of 24 living members were affected--QTc: 480-680 ms. The proband had long QTc, bilateral high-tone sensorineural deafness, recurrent syncope, and Torsades de Pointes. The asymptomatic father had long QTc and unilateral high-tone sensorineural deafness that involved specifically the left ear. One asymptomatic sibling of the proband had long QTc and normal hearing. The mother and another sibling were asymptomatic; QTc and hearing were normal in both. A total of 21 affected members from the extended family had only long QTc, and all were asymptomatic. There were three congenitally deaf first cousins who had recurrent syncope and adrenergic-triggered sudden death. In all, seven of 10 parents had consanguineous marriage to a first cousin. Each affected offspring had at least one affected parent. The severely symptomatic proband who received only β-blocker therapy and the 23 affected members without antiadrenergic therapy, all remained asymptomatic throughout the 16-year follow-up period. Jervell and Lange-Nielsen syndrome was inherited as autosomal dominant in this kindred. The majority of the affected members had a mild phenotype. The severity of auditory and cardiac phenotypes corresponded.

Unexplained sudden death, focussing on genetics and family phenotyping.

PubMed

Raju, Hariharan; Behr, Elijah R

2013-01-01

Unexplained sudden death and the sudden arrhythmic death syndrome (SADS) affect a small but significant proportion of young and apparently healthy individuals. This review revisits the causes underlying such deaths and the investigational strategies that identify surviving family who may be at risk. Recent epidemiological data is available from case series or government records. The yield from familial cardiological evaluation for inherited conditions has been supported by additional small series. The greatest advance has come with molecular autopsy studies, which have utilized various methodologies and candidate genes to investigate SADS cases and their families. The latest research replicates and extends the existing knowledge regarding epidemiology and familial evaluation of SADS, whilst genetic studies support a role for the molecular autopsy.

Family Child Care Licensing Study, 1997.

ERIC Educational Resources Information Center

Children's Foundation, Washington, DC.

This report details the findings of an annual survey of state child care regulatory agencies. The survey gathered data on both small family child care homes and group or large family child care homes in each of the 50 states, the District of Columbia, Puerto Rico and the Virgin Islands. The report's introduction lists the survey categories and…

Novel partial duplication of EYA1 causes branchiootic syndrome in a large Brazilian family.

PubMed

Dantas, Vitor G L; Freitas, Erika L; Della-Rosa, Valter A; Lezirovitz, Karina; de Moraes, Ana Maria S M; Ramos, Silvia B; Oiticica, Jeanne; Alves, Leandro U; Pearson, Peter L; Rosenberg, Carla; Mingroni-Netto, Regina C

2015-01-01

To identify novel genetic causes of syndromic hearing loss in Brazil. To map a candidate chromosomal region through linkage studies in an extensive Brazilian family and identify novel pathogenic variants using sequencing and array-CGH. Brazilian pedigree with individuals affected by BO syndrome characterized by deafness and malformations of outer, middle and inner ear, auricular and cervical fistulae, but no renal abnormalities. Whole genome microarray-SNP scanning on samples of 11 affected individuals detected a multipoint Lod score of 2.6 in the EYA1 gene region (chromosome 8). Sequencing of EYA1 in affected patients did not reveal pathogenic mutations. However, oligonucleotide-array-CGH detected a duplication of 71.8Kb involving exons 4 to 10 of EYA1 (heterozygous state). Real-time-PCR confirmed the duplication in fourteen of fifteen affected individuals and absence in 13 unaffected individuals. The exception involved a consanguineous parentage and was assumed to involve a different genetic mechanism. Our findings implicate this EYA1 partial duplication segregating with BO phenotype in a Brazilian pedigree and is the first description of a large duplication leading to the BOR/BO syndrome.

Robertsonian translocation between chromosomes (no.21/14) in relation to the history of spontaneous abortion in a family.

PubMed

Hasanzadeh-NazarAbadi, Mohammad; Baghbani, Fatemeh; Namazi, Iman; Mirzaee, Salmeh

2014-08-01

Approximately 205 million pregnancies occur each year in the worldwide. On the other hand, Spontaneous abortion has been reported in 15-20% of all diagnosed pregnancies. The most common cause of spontaneous abortion is chromosomal abnormalities of the embryo. Robertsonian translocation carriers specially 21-14 are the most common balanced rearrangement among the carrier couples with the history of spontaneous abortion. In order to search for balanced chromosomal rearrangement and cytogenetic disorders, 10 members of related family with consanguinity marriage with the history of recurrent miscarriage were assessed. Cytogenetic evaluation on the basis G-banding technique at high resolution was performed in 3 couples and their related family with the history of idiopathic RSA in order to postulate any balanced chromosomal rearrangement. six members of them appeared with robertsonian balanced translocation between chromosome No.21 to No. 14 with the karyotype of 45, XX, t (14, 21) and 45, XY, t (14, 21), which this results are in agreement with several similar works which claimed that the risk of spontaneous abortion in couples with balanced chromosomal rearrangements is higher compared with general population. Considering to results of present study, it seems as if the cytogenetic analysis of couples with the history of recurrent abortions should be suggested compulsory to estimate the probable presence of any chromosomal rearrangement. This offer wills valuable information for genetic consulting.

A resonant family of dynamically cold small bodies in the near-Earth asteroid belt

NASA Astrophysics Data System (ADS)

de la Fuente Marcos, C.; de la Fuente Marcos, R.

2013-07-01

Near-Earth objects (NEOs) moving in resonant, Earth-like orbits are potentially important. On the positive side, they are the ideal targets for robotic and human low-cost sample return missions and a much cheaper alternative to using the Moon as an astronomical observatory. On the negative side and even if small in size (2-50 m), they have an enhanced probability of colliding with the Earth causing local but still significant property damage and loss of life. Here, we show that the recently discovered asteroid 2013 BS45 is an Earth co-orbital, the sixth horseshoe librator to our planet. In contrast with other Earth's co-orbitals, its orbit is strikingly similar to that of the Earth yet at an absolute magnitude of 25.8, an artificial origin seems implausible. The study of the dynamics of 2013 BS45 coupled with the analysis of NEO data show that it is one of the largest and most stable members of a previously undiscussed dynamically cold group of small NEOs experiencing repeated trappings in the 1:1 commensurability with the Earth. This new resonant family is well constrained in orbital parameter space and it includes at least 10 other transient members: 2003 YN107, 2006 JY26, 2009 SH2 and 2012 FC71 among them. 2012 FC71 represents the best of both worlds as it is locked in a Kozai resonance and is unlikely to impact the Earth. These objects are not primordial and may have originated within the Venus-Earth-Mars region or in the main-belt, then transition to Amor-class asteroid before entering Earth's co-orbital region. Objects in this group could be responsible for the production of Earth's transient irregular natural satellites.

Deleterious Mutations in LRBA Are Associated with a Syndrome of Immune Deficiency and Autoimmunity

PubMed Central

Lopez-Herrera, Gabriela; Tampella, Giacomo; Pan-Hammarström, Qiang; Herholz, Peer; Trujillo-Vargas, Claudia M.; Phadwal, Kanchan; Simon, Anna Katharina; Moutschen, Michel; Etzioni, Amos; Mory, Adi; Srugo, Izhak; Melamed, Doron; Hultenby, Kjell; Liu, Chonghai; Baronio, Manuela; Vitali, Massimiliano; Philippet, Pierre; Dideberg, Vinciane; Aghamohammadi, Asghar; Rezaei, Nima; Enright, Victoria; Du, Likun; Salzer, Ulrich; Eibel, Hermann; Pfeifer, Dietmar; Veelken, Hendrik; Stauss, Hans; Lougaris, Vassilios; Plebani, Alessandro; Gertz, E. Michael; Schäffer, Alejandro A.; Hammarström, Lennart; Grimbacher, Bodo

2012-01-01

Most autosomal genetic causes of childhood-onset hypogammaglobulinemia are currently not well understood. Most affected individuals are simplex cases, but both autosomal-dominant and autosomal-recessive inheritance have been described. We performed genetic linkage analysis in consanguineous families affected by hypogammaglobulinemia. Four consanguineous families with childhood-onset humoral immune deficiency and features of autoimmunity shared genotype evidence for a linkage interval on chromosome 4q. Sequencing of positional candidate genes revealed that in each family, affected individuals had a distinct homozygous mutation in LRBA (lipopolysaccharide responsive beige-like anchor protein). All LRBA mutations segregated with the disease because homozygous individuals showed hypogammaglobulinemia and autoimmunity, whereas heterozygous individuals were healthy. These mutations were absent in healthy controls. Individuals with homozygous LRBA mutations had no LRBA, had disturbed B cell development, defective in vitro B cell activation, plasmablast formation, and immunoglobulin secretion, and had low proliferative responses. We conclude that mutations in LRBA cause an immune deficiency characterized by defects in B cell activation and autophagy and by susceptibility to apoptosis, all of which are associated with a clinical phenotype of hypogammaglobulinemia and autoimmunity. PMID:22608502

HomSI: a homozygous stretch identifier from next-generation sequencing data.

PubMed

Görmez, Zeliha; Bakir-Gungor, Burcu; Sagiroglu, Mahmut Samil

2014-02-01

In consanguineous families, as a result of inheriting the same genomic segments through both parents, the individuals have stretches of their genomes that are homozygous. This situation leads to the prevalence of recessive diseases among the members of these families. Homozygosity mapping is based on this observation, and in consanguineous families, several recessive disease genes have been discovered with the help of this technique. The researchers typically use single nucleotide polymorphism arrays to determine the homozygous regions and then search for the disease gene by sequencing the genes within this candidate disease loci. Recently, the advent of next-generation sequencing enables the concurrent identification of homozygous regions and the detection of mutations relevant for diagnosis, using data from a single sequencing experiment. In this respect, we have developed a novel tool that identifies homozygous regions using deep sequence data. Using *.vcf (variant call format) files as an input file, our program identifies the majority of homozygous regions found by microarray single nucleotide polymorphism genotype data. HomSI software is freely available at www.igbam.bilgem.tubitak.gov.tr/softwares/HomSI, with an online manual.

Birth order, family environments, academic and affective outcomes.

PubMed

Marjoribanks, Kevin

2003-06-01

Relations were examined among birth order, family social status, family learning environments, and a set of affective and academic outcomes. Data were collected as part of an Australian longitudinal study (4,171 females and 3,718 males). Analysis suggested that birth order continued to have small but significant associations with adolescents' self-concept and educational aspirations and with young adults' educational attainment, after taking into account differences in family social status and family learning environments.

Nonsyndromic retinitis pigmentosa is highly prevalent in the Jerusalem region with a high frequency of founder mutations

PubMed Central

Banin, Eyal

2015-01-01

Purpose Nonsyndromic retinitis pigmentosa (RP) is the most common inherited retinal degeneration, and prevalence of the disease has been reported in populations of American and European origin with a relatively low consanguinity rate. Our aim was to determine the prevalence of nonsyndromic RP in the Jerusalem region, which has a population of about 1 million individuals with a high rate of consanguinity. Methods The patients’ clinical data included eye exam findings (visual acuity, anterior segment, and funduscopy) as well as electroretinographic (ERG) testing results under scotopic and photopic conditions. Mutation analysis on a subgroup of patients was performed mainly with candidate gene analysis and homozygosity mapping. Results We evaluated the medical records of patients with degenerative retinal diseases residing in the Jerusalem region who were examined over the past 20 years in a large tertiary medical center. A total of 453 individuals affected with nonsyndromic RP were diagnosed at our center, according to funduscopic findings and ERG testing. Based on the estimated population size of 945,000 individuals who reside in the vicinity of Jerusalem, the prevalence of nonsyndromic RP in this region is 1:2,086. The prevalence of RP was higher among Arab Muslims (1:1,798) compared to Jews (1:2,230), mainly due to consanguineous marriages that are more common in the Arab Muslim population. To identify the genetic causes of RP in our cohort, we recruited 383 patients from 183 different families for genetic analysis: 70 with autosomal recessive (AR) inheritance, 15 with autosomal dominant, 86 isolate cases, and 12 with an X-linked inheritance pattern. In 64 (35%) of the families, we identified the genetic cause of the disease, and we revised the inheritance pattern of 20 isolate cases to the AR pattern; 49% of the families in our cohort had AR inheritance. Interestingly, in 42 (66%) of the genetically identified families, the cause of disease was a founder

Correlation between familial cancer history and epidermal growth factor receptor mutations in Taiwanese never smokers with non-small cell lung cancer: a case-control study.

PubMed

Cheng, Po-Chung; Cheng, Yun-Chung

2015-03-01

Lung cancer is a leading cause of cancer deaths in the world. Cigarette smoking remains a prominent risk factor, but lung cancer incidence has been increasing in never smokers. Genetic abnormalities including epidermal growth factor receptor (EGFR) mutations predominate in never smoking lung cancer patients. Furthermore, familial aggregations of patients with these mutations reflect heritable susceptibility to lung cancer. The correlation between familial cancer history and EGFR mutations in never smokers with lung cancer requires investigation. This was a retrospective case-control study that evaluated the prevalence of EGFR mutations in lung cancer patients with familial cancer history. Never smokers with lung cancer treated at a hospital in Taiwan between April 2012 and May 2014 were evaluated. Inclusion criteria were never smokers with non-small cell lung cancer (NSCLC). Exclusion criteria involved patients without records of familial cancer history or tumor genotype. This study included 246 never smokers with lung cancer. The study population mainly involved never smoking women with a mean age of 60 years, and the predominant tumor histology was adenocarcinoma. Lung cancer patients with familial cancer history had an increased prevalence of EGFR mutations compared to patients without family history [odds ratio (OR): 5.9; 95% confidence interval (CI): 3.3-10.6; P<0.001]. Specifically, 57 out of 85 cancer patients (67%) with familial cancer history had these mutations, while 41 out of 161 patients (25%) without family history harbored mutations. Subgroup analysis also revealed that patients with familial lung cancer history had stronger association with EGFR mutations (OR: 7.5; 95% CI: 3.4-16.3; P<0.001) compared to patients with family history of non-pulmonary cancers (OR: 5.0; 95% CI: 2.5-10.0; P<0.001). The study demonstrated an increased prevalence of EGFR mutations in Taiwanese never smoking lung cancer patients with familial cancer history. Moreover, a

State-of-the-art of small molecule inhibitors of the TAM family: the point of view of the chemist.

PubMed

Baladi, Tom; Abet, Valentina; Piguel, Sandrine

2015-11-13

The TAM family of tyrosine kinases receptors (Tyro3, Axl and Mer) is implicated in cancer development, autoimmune reactions and viral infection and is therefore emerging as an effective and attractive therapeutic target. To date, only a few small molecules have been intentionally designed to block the TAM kinases, while most of the inhibitors were developed for blocking different protein kinases and then identified through selectivity profile studies. This minireview will examine in terms of chemical structure the different compounds able to act on either one, two or three TAM kinases with details about structure-activity relationships, drug-metabolism and pharmacokinetics properties where they exist. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Lynch syndrome-related small intestinal adenocarcinomas.

PubMed

Jun, Sun-Young; Lee, Eui-Jin; Kim, Mi-Ju; Chun, Sung Min; Bae, Young Kyung; Hong, Soon Uk; Choi, Jene; Kim, Joon Mee; Jang, Kee-Taek; Kim, Jung Yeon; Kim, Gwang Il; Jung, Soo Jin; Yoon, Ghilsuk; Hong, Seung-Mo

2017-03-28

Lynch syndrome is an autosomal-dominant disorder caused by defective DNA mismatch repair (MMR) genes and is associated with increased risk of malignancies in multiple organs. Small-intestinal adenocarcinomas are common initial manifestations of Lynch syndrome. To define the incidence and characteristics of Lynch syndrome-related small-intestinal adenocarcinomas, meticulous familial and clinical histories were obtained from 195 patients with small-intestinal adenocarcinoma, and MMR protein immunohistochemistry, microsatellite instability, MLH1 methylation, and germline mutational analyses were performed. Lynch syndrome was confirmed in eight patients (4%), all of whom had synchronous/metachronous malignancies without noticeable familial histories. Small-intestinal adenocarcinomas were the first clinical manifestation in 37% (3/8) of Lynch syndrome patients, and second malignancies developed within 5 years in 63% (5/8). The patients with accompanying Lynch syndrome were younger (≤50 years; P=0.04) and more likely to have mucinous adenocarcinomas (P=0.003), and tended to survive longer (P=0.11) than those with sporadic cases. A meticulous patient history taking, MMR protein immunolabeling, and germline MMR gene mutational analysis are important for the diagnosis of Lynch syndrome-related small-intestinal adenocarcinomas. Identifying Lynch syndrome in patients with small-intestinal adenocarcinoma can be beneficial for the early detection and treatment of additional Lynch syndrome-related cancers, especially in patients who are young or have mucinous adenocarcinomas.

Lynch syndrome-related small intestinal adenocarcinomas

PubMed Central

Jun, Sun-Young; Lee, Eui-Jin; Kim, Mi-Ju; Chun, Sung Min; Bae, Young Kyung; Hong, Soon Uk; Choi, Jene; Kim, Joon Mee; Jang, Kee-Taek; Kim, Jung Yeon; Kim, Gwang Il; Jung, Soo Jin; Yoon, Ghilsuk; Hong, Seung-Mo

2017-01-01

Lynch syndrome is an autosomal-dominant disorder caused by defective DNA mismatch repair (MMR) genes and is associated with increased risk of malignancies in multiple organs. Small-intestinal adenocarcinomas are common initial manifestations of Lynch syndrome. To define the incidence and characteristics of Lynch syndrome-related small-intestinal adenocarcinomas, meticulous familial and clinical histories were obtained from 195 patients with small-intestinal adenocarcinoma, and MMR protein immunohistochemistry, microsatellite instability, MLH1 methylation, and germline mutational analyses were performed. Lynch syndrome was confirmed in eight patients (4%), all of whom had synchronous/metachronous malignancies without noticeable familial histories. Small-intestinal adenocarcinomas were the first clinical manifestation in 37% (3/8) of Lynch syndrome patients, and second malignancies developed within 5 years in 63% (5/8). The patients with accompanying Lynch syndrome were younger (≤50 years; P=0.04) and more likely to have mucinous adenocarcinomas (P=0.003), and tended to survive longer (P=0.11) than those with sporadic cases. A meticulous patient history taking, MMR protein immunolabeling, and germline MMR gene mutational analysis are important for the diagnosis of Lynch syndrome-related small-intestinal adenocarcinomas. Identifying Lynch syndrome in patients with small-intestinal adenocarcinoma can be beneficial for the early detection and treatment of additional Lynch syndrome-related cancers, especially in patients who are young or have mucinous adenocarcinomas. PMID:28206961

Targeted next-generation sequencing identifies a homozygous nonsense mutation in ABHD12, the gene underlying PHARC, in a family clinically diagnosed with Usher syndrome type 3.

PubMed

Eisenberger, Tobias; Slim, Rima; Mansour, Ahmad; Nauck, Markus; Nürnberg, Gudrun; Nürnberg, Peter; Decker, Christian; Dafinger, Claudia; Ebermann, Inga; Bergmann, Carsten; Bolz, Hanno Jörn

2012-09-02

Usher syndrome (USH) is an autosomal recessive genetically heterogeneous disorder with congenital sensorineural hearing impairment and retinitis pigmentosa (RP). We have identified a consanguineous Lebanese family with two affected members displaying progressive hearing loss, RP and cataracts, therefore clinically diagnosed as USH type 3 (USH3). Our study was aimed at the identification of the causative mutation in this USH3-like family. Candidate loci were identified using genomewide SNP-array-based homozygosity mapping followed by targeted enrichment and next-generation sequencing. Using a capture array targeting the three identified homozygosity-by-descent regions on chromosomes 1q43-q44, 20p13-p12.2 and 20p11.23-q12, we identified a homozygous nonsense mutation, p.Arg65X, in ABHD12 segregating with the phenotype. Mutations of ABHD12, an enzyme hydrolyzing an endocannabinoid lipid transmitter, cause PHARC (polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and early-onset cataract). After the identification of the ABHD12 mutation in this family, one patient underwent neurological examination which revealed ataxia, but no polyneuropathy. ABHD12 is not known to be related to the USH protein interactome. The phenotype of our patient represents a variant of PHARC, an entity that should be taken into account as differential diagnosis for USH3. Our study demonstrates the potential of comprehensive genetic analysis for improving the clinical diagnosis.

Exome analysis identified a novel mutation in the RBP4 gene in a consanguineous pedigree with retinal dystrophy and developmental abnormalities.

PubMed

Cukras, Catherine; Gaasterland, Terry; Lee, Pauline; Gudiseva, Harini V; Chavali, Venkata R M; Pullakhandam, Raghu; Maranhao, Bruno; Edsall, Lee; Soares, Sandra; Reddy, G Bhanuprakash; Sieving, Paul A; Ayyagari, Radha

2012-01-01

Retinitis Pigmentosa (RP) is a common form of retinal degeneration characterized by photoreceptor degeneration and retinal pigment epithelium (RPE) atrophy causing loss of visual field and acuities. Exome sequencing identified a novel homozygous splice site variant (c.111+1G>A) in the gene encoding retinol binding protein 4 (RBP4). This change segregated with early onset, progressive, and severe autosomal recessive retinitis pigmentosa (arRP) in an eight member consanguineous pedigree of European ancestry. Additionally, one patient exhibited developmental abnormalities including patent ductus arteriosus and chorioretinal and iris colobomas. The second patient developed acne from young age and extending into the 5(th) decade. Both patients had undetectable levels of RBP4 in the serum suggesting that this mutation led to either mRNA or protein instability resulting in a null phenotype. In addition, the patients exhibited severe vitamin A deficiency, and diminished serum retinol levels. Circulating transthyretin levels were normal. This study identifies the RBP4 splice site change as the cause of RP in this pedigree. The presence of developmental abnormalities and severe acne in patients with retinal degeneration may indicate the involvement of genes that regulate vitamin A absorption, transport and metabolism.

Exome Analysis Identified a Novel Mutation in the RBP4 Gene in a Consanguineous Pedigree with Retinal Dystrophy and Developmental Abnormalities

PubMed Central

Cukras, Catherine; Gaasterland, Terry; Lee, Pauline; Gudiseva, Harini V.; Chavali, Venkata R. M.; Pullakhandam, Raghu; Maranhao, Bruno; Edsall, Lee; Soares, Sandra; Reddy, G. Bhanuprakash; Sieving, Paul A.; Ayyagari, Radha

2012-01-01

Retinitis Pigmentosa (RP) is a common form of retinal degeneration characterized by photoreceptor degeneration and retinal pigment epithelium (RPE) atrophy causing loss of visual field and acuities. Exome sequencing identified a novel homozygous splice site variant (c.111+1G>A) in the gene encoding retinol binding protein 4 (RBP4). This change segregated with early onset, progressive, and severe autosomal recessive retinitis pigmentosa (arRP) in an eight member consanguineous pedigree of European ancestry. Additionally, one patient exhibited developmental abnormalities including patent ductus arteriosus and chorioretinal and iris colobomas. The second patient developed acne from young age and extending into the 5th decade. Both patients had undetectable levels of RBP4 in the serum suggesting that this mutation led to either mRNA or protein instability resulting in a null phenotype. In addition, the patients exhibited severe vitamin A deficiency, and diminished serum retinol levels. Circulating transthyretin levels were normal. This study identifies the RBP4 splice site change as the cause of RP in this pedigree. The presence of developmental abnormalities and severe acne in patients with retinal degeneration may indicate the involvement of genes that regulate vitamin A absorption, transport and metabolism. PMID:23189188

Next generation sequencing identifies mutations in Atonal homolog 7 (ATOH7) in families with global eye developmental defects

PubMed Central

Khan, Kamron; Logan, Clare V.; McKibbin, Martin; Sheridan, Eamonn; Elçioglu, Nursel H.; Yenice, Ozlem; Parry, David A.; Fernandez-Fuentes, Narcis; Abdelhamed, Zakia I.A.; Al-Maskari, Ahmed; Poulter, James A.; Mohamed, Moin D.; Carr, Ian M.; Morgan, Joanne E.; Jafri, Hussain; Raashid, Yasmin; Taylor, Graham R.; Johnson, Colin A.; Inglehearn, Chris F.; Toomes, Carmel; Ali, Manir

2012-01-01

The atonal homolog 7 (ATOH7) gene encodes a transcription factor involved in determining the fate of retinal progenitor cells and is particularly required for optic nerve and ganglion cell development. Using a combination of autozygosity mapping and next generation sequencing, we have identified homozygous mutations in this gene, p.E49V and p.P18RfsX69, in two consanguineous families diagnosed with multiple ocular developmental defects, including severe vitreoretinal dysplasia, optic nerve hypoplasia, persistent fetal vasculature, microphthalmia, congenital cataracts, microcornea, corneal opacity and nystagmus. Most of these clinical features overlap with defects in the Norrin/β-catenin signalling pathway that is characterized by dysgenesis of the retinal and hyaloid vasculature. Our findings document Mendelian mutations within ATOH7 and imply a role for this molecule in the development of structures at the front as well as the back of the eye. This work also provides further insights into the function of ATOH7, especially its importance in retinal vascular development and hyaloid regression. PMID:22068589

Genetic investigation of 93 families with microphthalmia or posterior microphthalmos.

PubMed

Patel, N; Khan, A O; Alsahli, S; Abdel-Salam, G; Nowilaty, S R; Mansour, A M; Nabil, A; Al-Owain, M; Sogati, S; Salih, M A; Kamal, A M; Alsharif, H; Alsaif, H S; Alzahrani, S S; Abdulwahab, F; Ibrahim, N; Hashem, M; Faquih, T; Shah, Z A; Abouelhoda, M; Monies, D; Dasouki, M; Shaheen, R; Wakil, S M; Aldahmesh, M A; Alkuraya, F S

2018-06-01

Microphthalmia is a developmental eye defect that is highly variable in severity and in its potential for systemic association. Despite the discovery of many disease genes in microphthalmia, at least 50% of patients remain undiagnosed genetically. Here, we describe a cohort of 147 patients (93 families) from our highly consanguineous population with various forms of microphthalmia (including the distinct entity of posterior microphthalmos) that were investigated using a next-generation sequencing multi-gene panel (i-panel) as well as whole exome sequencing and molecular karyotyping. A potentially causal mutation was identified in the majority of the cohort with microphthalmia (61%) and posterior microphthalmos (82%). The identified mutations (55 point mutations, 15 of which are novel) spanned 24 known disease genes, some of which have not or only very rarely been linked to microphthalmia (PAX6, SLC18A2, DSC3 and CNKSR1). Our study has also identified interesting candidate variants in 2 genes that have not been linked to human diseases (MYO10 and ZNF219), which we present here as novel candidates for microphthalmia. In addition to revealing novel phenotypic aspects of microphthalmia, this study expands its allelic and locus heterogeneity and highlights the need for expanded testing of patients with this condition. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A novel mutation in exon 2 of FGB caused by c.221G>T † substitution, predicting the replacement of the native Arginine at position 74 with a Leucine (p.Arg74Leu † ) in a proband from a Kurdish family with dysfibrinogenaemia and familial venous and arterial thrombosis.

PubMed

Shlebak, Abdul A; Katsarou, Alexia D; Adams, George; Fernando, Fiona

2017-02-01

Dysfibrinogenaemias may present in either congenital or acquired form and are disorders of fibrinogen structure which may or may not be associated with abnormal function. More than 100 point mutations with single amino acid substitutions have been identified in over 400 families. These lead to defective DNA in the translated fibrinogen molecule. Such cases have improved our understanding of the fibrinogen-fibrin structure. Six members of a consanguineous family including a female proband, a female sibling, three male siblings and a daughter, with ages between 29 years and 53 years presented with early onset venous and premature arterial thromboembolic disease were investigated for a pro-thrombotic tendency associated with dysfibrinogenaemia. The family was investigated using standard coagulation assays and DNA sequencing of the genes encoding the FGA, FGB and FGG. All cases have dysfibrinogenaemia with a fibrinogen level 1.4 to 1.5 (1.9-4.3 g/L). Thrombophilia testing (including AT, PS & PC, F5 G1691A (FV Leiden)/F2 (prothombin G20210A) genotypes, homocysteine, antiphosphlipid antibody, paroxysmal nocturnal haemoglobinuria by flow cytometry and Janus Kinase-2 (exon 14)) were normal. PCR amplification and sequencing of exon 2 of FBG revealed a heterozygous mutation for a c.221G> T † substitution, predicting the replacement of the native Arginine at position 74 with a Leucine (p.Arg74Leu † ). In silico analysis of p.Arg74Leu strongly support pathogenicity. A novel mutation was identified in exon 2 of FGB caused by c.221G> T † substitution, predicting the replacement of Arginine at position 74 with a Leucine (p.Arg74Leu † ) in a proband from a Kurdish family with dysfibrinogenaemia and familial venous and arterial thrombosis.

Tandem Duplication Events in the Expansion of the Small Heat Shock Protein Gene Family in Solanum lycopersicum (cv. Heinz 1706)

PubMed Central

Krsticevic, Flavia J.; Arce, Débora P.; Ezpeleta, Joaquín; Tapia, Elizabeth

2016-01-01

In plants, fruit maturation and oxidative stress can induce small heat shock protein (sHSP) synthesis to maintain cellular homeostasis. Although the tomato reference genome was published in 2012, the actual number and functionality of sHSP genes remain unknown. Using a transcriptomic (RNA-seq) and evolutionary genomic approach, putative sHSP genes in the Solanum lycopersicum (cv. Heinz 1706) genome were investigated. A sHSP gene family of 33 members was established. Remarkably, roughly half of the members of this family can be explained by nine independent tandem duplication events that determined, evolutionarily, their functional fates. Within a mitochondrial class subfamily, only one duplicated member, Solyc08g078700, retained its ancestral chaperone function, while the others, Solyc08g078710 and Solyc08g078720, likely degenerated under neutrality and lack ancestral chaperone function. Functional conservation occurred within a cytosolic class I subfamily, whose four members, Solyc06g076570, Solyc06g076560, Solyc06g076540, and Solyc06g076520, support ∼57% of the total sHSP RNAm in the red ripe fruit. Subfunctionalization occurred within a new subfamily, whose two members, Solyc04g082720 and Solyc04g082740, show heterogeneous differential expression profiles during fruit ripening. These findings, involving the birth/death of some genes or the preferential/plastic expression of some others during fruit ripening, highlight the importance of tandem duplication events in the expansion of the sHSP gene family in the tomato genome. Despite its evolutionary diversity, the sHSP gene family in the tomato genome seems to be endowed with a core set of four homeostasis genes: Solyc05g014280, Solyc03g082420, Solyc11g020330, and Solyc06g076560, which appear to provide a baseline protection during both fruit ripening and heat shock stress in different tomato tissues. PMID:27565886

Small GTPases and Stress Responses of vvran1 in the Straw Mushroom Volvariella volvacea

PubMed Central

Yan, Jun-Jie; Xie, Bin; Zhang, Lei; Li, Shao-Jie; van Peer, Arend F.; Wu, Ta-Ju; Chen, Bing-Zhi; Xie, Bao-Gui

2016-01-01

Small GTPases play important roles in the growth, development and environmental responses of eukaryotes. Based on the genomic sequence of the straw mushroom Volvariella volvacea, 44 small GTPases were identified. A clustering analysis using human small GTPases as the references revealed that V. volvacea small GTPases can be grouped into five families: nine are in the Ras family, 10 are in the Rho family, 15 are in the Rab family, one is in the Ran family and nine are in the Arf family. The transcription of vvran1 was up-regulated upon hydrogen peroxide (H2O2) stress, and could be repressed by diphenyleneiodonium chloride (DPI), a NADPH oxidase-specific inhibitor. The number of vvran1 transcripts also increased upon cold stress. Diphenyleneiodonium chloride, but not the superoxide dismutase (SOD) inhibitor diethy dithiocarbamate (DDC), could suppress the up-regulation of vvran1 gene expression to cold stress. These results combined with the high correlations between gene expression and superoxide anion (O2−) generation indicated that vvran1 could be one of the candidate genes in the downstream of O2− mediated pathways that are generated by NADPH oxidase under low temperature and oxidative stresses. PMID:27626406

Structural and functional studies of a family of Dictyostelium discoideum developmentally regulated, prestalk genes coding for small proteins.

PubMed

Vicente, Juan J; Galardi-Castilla, María; Escalante, Ricardo; Sastre, Leandro

2008-01-03

The social amoeba Dictyostelium discoideum executes a multicellular development program upon starvation. This morphogenetic process requires the differential regulation of a large number of genes and is coordinated by extracellular signals. The MADS-box transcription factor SrfA is required for several stages of development, including slug migration and spore terminal differentiation. Subtractive hybridization allowed the isolation of a gene, sigN (SrfA-induced gene N), that was dependent on the transcription factor SrfA for expression at the slug stage of development. Homology searches detected the existence of a large family of sigN-related genes in the Dictyostelium discoideum genome. The 13 most similar genes are grouped in two regions of chromosome 2 and have been named Group1 and Group2 sigN genes. The putative encoded proteins are 87-89 amino acids long. All these genes have a similar structure, composed of a first exon containing a 13 nucleotides long open reading frame and a second exon comprising the remaining of the putative coding region. The expression of these genes is induced at10 hours of development. Analyses of their promoter regions indicate that these genes are expressed in the prestalk region of developing structures. The addition of antibodies raised against SigN Group 2 proteins induced disintegration of multi-cellular structures at the mound stage of development. A large family of genes coding for small proteins has been identified in D. discoideum. Two groups of very similar genes from this family have been shown to be specifically expressed in prestalk cells during development. Functional studies using antibodies raised against Group 2 SigN proteins indicate that these genes could play a role during multicellular development.

IRAS asteroid families

NASA Technical Reports Server (NTRS)

Veeder, G. J.; Williams, J. G.; Tedesco, E. F.; Matson, D. L.

1991-01-01

The Infrared Astronomical Satellite (IRAS) sampled the entire asteroid population at wavelengths from 12 to 100 microns during its 1983 all sky survey. The IRAS Minor Planet Survey (IMPS) includes updated results for more recently numbered as well as other additional asteroids with reliable orbital elements. Albedos and diameters were derived from the observed thermal emission and assumed absolute visual magnitudes and then entered into the IMPS database at the Infrared Processing and Analysis Center (IPAC) for members of the Themis, Eos, Koronis and Maria asteroid families and compared with their visual colors. The IMPS results for the small (down to about 20 km) asteroids within these major families confirm trends previously noted for their larger members. Each of these dynamical families which are defined by their similar proper elements appears to have homogeneous physical properties.

Thioredoxin Reductase 2 (TXNRD2) mutation associated with familial glucocorticoid deficiency (FGD).

PubMed

Prasad, Rathi; Chan, Li F; Hughes, Claire R; Kaski, Juan P; Kowalczyk, Julia C; Savage, Martin O; Peters, Catherine J; Nathwani, Nisha; Clark, Adrian J L; Storr, Helen L; Metherell, Louise A

2014-08-01

Classic ACTH resistance, due to disruption of ACTH signaling, accounts for the majority of cases of familial glucocorticoid deficiency (FGD). Recently FGD cases caused by mutations in the mitochondrial antioxidant, nicotinamide nucleotide transhydrogenase, have highlighted the importance of redox regulation in steroidogenesis. We hypothesized that other components of mitochondrial antioxidant systems would be good candidates in the etiology of FGD. Whole-exome sequencing was performed on three related patients, and segregation of putative causal variants confirmed by Sanger sequencing of all family members. A TXNRD2-knockdown H295R cell line was created to investigate redox homeostasis. The study was conducted on patients from three pediatric centers in the United Kingdom. Seven individuals from a consanguineous Kashmiri kindred, six of whom presented with FGD between 0.1 and 10.8 years, participated in the study. There were no interventions. Identification and functional interrogation of a novel homozygous mutation segregating with the disease trait were measured. A stop gain mutation, p.Y447X in TXNRD2, encoding the mitochondrial selenoprotein thioredoxin reductase 2 (TXNRD2) was identified and segregated with disease in this extended kindred. RT-PCR and Western blotting revealed complete absence of TXNRD2 in patients homozygous for the mutation. TXNRD2 deficiency leads to impaired redox homeostasis in a human adrenocortical cell line. In contrast to the Txnrd2-knockout mouse model, in which embryonic lethality as a consequence of hematopoietic and cardiac defects is described, absence of TXNRD2 in humans leads to glucocorticoid deficiency. This is the first report of a homozygous mutation in any component of the thioredoxin antioxidant system leading to inherited disease in humans.

The change of family size and structure in China.

PubMed

1992-04-01

With the socioeconomic development and change of people's values, there is some significant change in family size and structure in China. According to the 10% sample data from the 4th Census, 1 family has 3.97 persons on an average, less than the 3rd Census by 0.44 persons; among all types of families, 1-generation families account for 13.5%, 3 generation families for 18.5%, and 2-generation families account for 68%. Instead of large families consisting of several generations and many members, small families has now become a principal family type in China. According to the analysis of the sample data from the 4th Census, the family size is mainly decided by the fertility level in particular regions, and it also depends on the economic development. So family size is usually smaller in more developed regions, such as in Beijing, Tianjin, Zhejiang, Liaoning as well as in Shanghai of which family size is only 3.08 persons; and family size is generally larger in less developed regions such as in Qinghai, Guangxi, Gansu, Xinjiang, and in Tibet of which family size is as large as 5.13 persons. Specialists regard the increase of the number of families as 1 of the major consequences of the economic development, change of living style, and improvement of living standard, Young people now are more inclined to live separately from their parents. However, the increase of the number of families will undoubtedly place more pressure on housing and require more furniture and other durable consumer goods from the market. Therefore, the government and other social sectors related should make corresponding plans and policies to cope with the increase of families and minifying of family size so as to promote family planning and socioeconomic development, and to create better social circumstances for small families. full text

Wellness in Small Businesses. WBGH Worksite Wellness Series.