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Sample records for recessive inheritance case

  1. Congenital vocal cord paralysis with possible autosomal recessive inheritance: Case report and review of the literature

    SciTech Connect

    Koppel, R.; Friedman, S.; Fallet, S.

    1996-08-23

    We describe an infant with congenital vocal cord paralysis born to consanguineous parents. While autosomal dominant and X-linked inheritance have been previously reported in this condition, we conclude that the degree of parental consanguinity in this case strongly suggests autosomal recessive inheritance. Although we cannot exclude X-linked inheritance, evidence from animal studies demonstrates autosomal recessive inheritance and provides a possible molecular basis for congenital vocal cord paralysis. 14 refs., 1 fig.

  2. Recessive inheritance of a relative fat pattern.

    PubMed Central

    Hasstedt, S J; Ramirez, M E; Kuida, H; Williams, R R

    1989-01-01

    We defined a relative-fat-pattern index (RFPI) as the ratio of subscapular skinfold thickness to the sum of subscapular and suprailiac skinfold thicknesses and computed RFPI for 774 adults (age greater than or equal to 25 years) in 59 pedigrees ascertained through cases of cardiovascular disease. Likelihood analysis of RFPI supported recessive inheritance of an allele with a frequency of 46%, which elevated mean RFPI from .412 to .533 when homozygous. The analysis apportioned the variance in RFPI as 42.3% due to the major locus, 9.5% due to polygenic inheritance, and 48.2% due to random environmental effects. Homozygotes for the recessive allele tended to have small suprailiac skinfold thicknesses rather than large subscapular skinfold thicknesses. Homozygotes were more frequent in younger than in older cases of obesity, coronary heart disease, essential hypertension, and diabetes mellitus; the increase was significant for all but diabetes. PMID:2589320

  3. Evidence for autosomal recessive inheritance in cerebral gigantism

    PubMed Central

    Nevo, S.; Zeltzer, M.; Benderly, A.; Levy, J.

    1974-01-01

    Three cases of cerebral gigantism, two sibs and their double first cousin, are described in a large inbred family from Israel. Two of the three were observed and diagnosed at birth and two were followed for two years. They all presented the signs and symptoms considered typical of this syndrome, as well as some of the less frequent findings. Generalized oedema and flexion contractures of the feet were observed in two of the three at birth. This has not hitherto been reported in cases of cerebral gigantism, of whom only a few have been observed and diagnosed at birth. Autosomal recessive inheritance is clearly implied in this family. Images PMID:4841084

  4. Additional case of Marden-Walker syndrome: support for the autosomal-recessive inheritance adn refinement of phenotype in a surviving patient.

    PubMed

    Orrico, A; Galli, L; Zappella, M; Orsi, A; Hayek, G

    2001-02-01

    In this report, we present a 14-year-old girl, born to consanguineous parents, who presented with severe mental retardation, hypotonia, short stature, and congenital joint contractures. The craniofacial features were scaphocephaly, thin/long and immobile face, marked hypoplasia of the midface, temporal narrowness, blepharophimosis, palpebral ptosis, and strabismus. The combination of such a distinctive craniofacial appearance and psychomotor retardation allows us to recognize a new case of the Marden-Walker syndrome. Our patient represents one of the rare cases in which consanguineous mating supports the autosomal-recessive pattern of inheritance of this condition. Furthermore, through refining the phenotype of a surviving patient, this report may contribute to a better recognition of this disorder in older affected children.

  5. Arthrogryposis Multiplex Congenita: Neurogenic Type with Autosomal Recessive Inheritance

    PubMed Central

    Rosenmann, A.; Arad, I.

    1974-01-01

    An infant affected by severe arthrogryposis multiplex congenita leading to death in infancy due to neurogenic atrophy is described. Six other sibs were similarly affected. An autosomal recessive mode of inheritance is suggested. Images PMID:4837288

  6. The Autosomal Recessive Inheritance of Hereditary Gingival Fibromatosis

    PubMed Central

    Nair, Vineet; Mukherjee, Malancha; Ghosh, Sujoy; Dey, Subrata Kumar

    2013-01-01

    Hereditary gingival fibromatosis (HGF) is a rare condition which is marked by enlargement of gingival tissue that covers teeth to various extents leading to aesthetic disfigurement. This study presents a case of a 28-year-old female patient and 18-year-old male who belong to the same family suffering from HGF with chief complaint of overgrowing swelling gingiva. The presence of enlarged gingiva with the same eruption was found in their other family members with no concomitant drug or medical history, and the occurrence of HGF has been found in one generation of this family which may indicate the autosomal recessive inheritance pattern of HGF. Hereditary gingival fibromatosis is an idiopathic condition as its etiology is unknown and it was found to recur in some cases even after surgical treatment. Both patients underwent thorough oral prophylaxis and later surgical therapy to correct the deformity. PMID:24416600

  7. Recessive inheritance of the adult type of intestinal lactase deficiency.

    PubMed Central

    Lisker, R; Gonzalez, B; Daltabuit, M

    1975-01-01

    In order to investigate the genetic control of the adult type of intestinal lactase deficiency, 61 families with 177 children over 6 years of age were investigated. The results strongly suggest that this deficiency is inherited as a simple Mendelian recessive trait. PMID:1163538

  8. Syndrome of mental retardation, seizures, hypotonic cerebral palsy and megalocorneae, recessively inherited.

    PubMed

    Neuhäuser, G; Kaveggia, E G; France, T D; Opitz, J M

    1975-07-01

    A previously apparently undescribed "syndrome" is reported in which megalocornea and iris anomalies are accompanied by minor facial and skeletal anomalies, severe mental retardation, hypotonia, and seizures. The condition was found in 3 siblings of one family and in 4 sporadic cases; it is thought to be recessively inherited.

  9. Familial olivopontocerebellar atrophy with neonatal onset: a recessively inherited syndrome with systemic and biochemical abnormalities.

    PubMed Central

    Harding, B N; Dunger, D B; Grant, D B; Erdohazi, M

    1988-01-01

    Clinical and pathological findings are reported in two siblings who presented in the neonatal period with failure to thrive, hypotonia, pericardial effusions, limitation of joint movement, retinal dystrophy and loss of visual function. Additional features were biochemical evidence of purine overproduction and liver dysfunction. Post mortem, the neuropathological findings in both children were typical of olivopontocerebellar atrophy. It is suggested that the cases represent a recessively inherited inborn error of metabolism. Images PMID:3162953

  10. Recessive inherited doubling of the chicken's uropygial gland papilla.

    PubMed

    Somes, R G

    1991-01-01

    A new mutation that causes doubling of the uropygial gland (oil gland) papilla is described, and data that demonstrate its inherited basis are presented. This condition, which has been given the name "double oil gland papilla," varies in its expression: some individuals show only an indention of the papilla tip, while others exhibit a complete cleavage of the papilla such that two completely separate papillae project from a single oil gland. The data presented show that a single autosomal recessive gene, dgp, is the main determinant of this trait, but that its expression may also be influenced by background genetic factors as well as sex. Males more frequently are of the extreme doubling expression while females more frequently express the milder indented phenotype. Approximately 4% of mutant females are classified as normal. A linkage test with the rose comb gene showed independent segregation.

  11. Recessively Inherited LRBA Mutations Cause Autoimmunity Presenting as Neonatal Diabetes.

    PubMed

    Johnson, Matthew B; De Franco, Elisa; Lango Allen, Hana; Al Senani, Aisha; Elbarbary, Nancy; Siklar, Zeynep; Berberoglu, Merih; Imane, Zineb; Haghighi, Alireza; Razavi, Zahra; Ullah, Irfan; Alyaarubi, Saif; Gardner, Daphne; Ellard, Sian; Hattersley, Andrew T; Flanagan, Sarah E

    2017-08-01

    Young-onset autoimmune diabetes associated with additional autoimmunity usually reflects a polygenic predisposition, but rare cases result from monogenic autoimmunity. Diagnosing monogenic autoimmunity is crucial for patients' prognosis and clinical management. We sought to identify novel genetic causes of autoimmunity presenting with neonatal diabetes (NDM) (diagnosis <6 months). We performed exome sequencing in a patient with NDM and autoimmune lymphoproliferative syndrome and his unrelated, unaffected parents and identified compound heterozygous null mutations in LRBA Biallelic LRBA mutations cause common variable immunodeficiency-8; however, NDM has not been confirmed in this disorder. We sequenced LRBA in 169 additional patients with diabetes diagnosed <1 year without mutations in the 24 known NDM genes. We identified recessive null mutations in 8 additional probands, of which, 3 had NDM (<6 months). Diabetes was the presenting feature in 6 of 9 probands. Six of 17 (35%) patients born to consanguineous parents and with additional early-onset autoimmunity had recessive LRBA mutations. LRBA testing should be considered in patients with diabetes diagnosed <12 months, particularly if they have additional autoimmunity or are born to consanguineous parents. A genetic diagnosis is important as it can enable personalized therapy with abatacept, a CTLA-4 mimetic, and inform genetic counseling. © 2017 by the American Diabetes Association.

  12. Short stature, brachydactyly, and Peters' anomaly (Peters'-plus syndrome): confirmation of autosomal recessive inheritance.

    PubMed Central

    de Almeida, J C; Reis, D F; Llerena Júnior, J; Barbosa Neto, J; Pontes, R L; Middleton, S; Telles, L F

    1991-01-01

    Two sibs with a phenotype characterised by short stature, brachydactyly, and ocular anomalies (Peters' anomaly) are reported (Peters'-plus syndrome). The consanguinity is in agreement with the proposed autosomal recessive inheritance. Images PMID:1856836

  13. Understanding the cellular and molecular mechanisms of dominant and recessive inheritance in genetics course.

    PubMed

    Wanjin, Xing; Morigen, Morigen

    2015-01-01

    In Mendellian genetics, the dominance and recessiveness are used to describe the functional relationship between two alleles of one gene in a heterozygote. The allele which constitutes a phenotypical character over the other is named dominant and the one functionally masked is called recessive. The definitions thereby led to the creation of Mendel's laws on segregation and independent assortment and subsequent classic genetics. The discrimination of dominance and recessiveness originally is a requirement for Mendel's logical reasoning, but now it should be explained by cellular and molecular principles in the modern genetics. To answer the question raised by students of how the dominance and recessiveness are controlled, we reviewed the recent articles and tried to summarize the cellular and molecular basis of dominant and recessive inheritance. Clearly, understanding the essences of dominant and recessive inheritance requires us to know the dissimilarity of the alleles and their products (RNA and/or proteins), and the way of their function in cells. The alleles spatio-temporally play different roles on offering cells, tissues or organs with discernible phenotypes, namely dominant or recessive. Here, we discuss the changes of allele dominance and recessiveness at the cellular and molecular levels based on the variation of gene structure, gene regulation, function and types of gene products, in order to make students understand gene mutation and function more comprehensively and concretely.

  14. Diagnostic value of ultrastructural nerve examination in Charcot-Marie-Tooth disease: two CMT 1B cases with pseudo-recessive inheritance.

    PubMed

    Vallat, Jean-Michel; Magy, Laurent; Lagrange, Emmeline; Sturtz, Franck; Magdelaine, Corinne; Grid, Djamel; Tazir, Mériem

    2007-04-01

    We report two sporadic patients of CMT disease in different consanguineous families. The electrophysiological examination led to the diagnosis of a severe demyelinating neuropathy. The nerve biopsies exhibited numerous outfoldings of the myelin sheaths and onion-bulb proliferations. The consanguinity and the histological findings pointed to a diagnosis of CMT 4B. However, the detection of abnormal and regular widenings between the major dense lines of the myelin lamellae by electron microscopy led us to search for a P0 gene mutation. Two heterozygous mutations of this gene were identified: S63F and N131Y. Different aspects of uncompacted myelin lamellae have been described in some cases of P0 mutations and a few now appear to be quite specific to it. More than 30 genes are implicated in CMT and as mutation search is time- and money-consuming, we believe that in some selected patients ultrastructural examination of nerves, among other criteria, helps orientate the molecular diagnosis of CMT.

  15. Unstable minisatellite expansion causing recessively inherited myoclonus epilepsy, EPM1.

    PubMed

    Virtaneva, K; D'Amato, E; Miao, J; Koskiniemi, M; Norio, R; Avanzini, G; Franceschetti, S; Michelucci, R; Tassinari, C A; Omer, S; Pennacchio, L A; Myers, R M; Dieguez-Lucena, J L; Krahe, R; de la Chapelle, A; Lehesjoki, A E

    1997-04-01

    Progressive myoclonus epilepsy of Unverricht-Lundborg type (EPM1; MIM 254800) is an autosomal recessive disorder that occurs with a low frequency in many populations but is more common in Finland and the Mediterranean region. It is characterized by stimulus-sensitive myoclonus and tonic-clonic seizures with onset at age 6-15 years, typical electroencephalographic abnormalities and a variable rate of progression between and within families. Following the initial mapping of the EPM1 gene to chromosome 21 (ref. 6) and the refinement of the critical region to a small interval, positional cloning identified the gene encoding cystatin B (CST6), a cysteine protease inhibitor, as the gene underlying EPM1 (ref. 10). Levels of messenger RNA encoded by CST6 were dramatically decreased in patients. A 3' splice site and a stop codon mutation were identified in three families, leaving most mutations uncharacterized. In this study, we report a novel type of disease-causing mutation, an unstable 15- to 18-mer minisatellite repeat expansion in the putative promoter region of the CST6 gene. The mutation accounts for the majority of EPM1 patients worldwide. Haplotype data are compatible with a single ancestral founder mutation. The length of the repeat array differs between chromosomes and families, but changes in repeat number seem to be comparatively rare events.

  16. Dominant and recessive inheritance patterns of diapause in the two-spotted spider mite Tetranychus urticae.

    PubMed

    Kawakami, Yuko; Numata, Hideharu; Ito, Katsura; Goto, Shin G

    2010-01-01

    In this study, we investigated the diapause incidence in 3 geographic strains of the two-spotted spider mite Tetranychus urticae (Acari: Tetranychidae). Under diapause-inducing conditions of 12:12 light:dark at 15 degrees C, the diapause incidence was nearly 100% in a strain from northern Japan (Sapporo), whereas it was nearly 0% in 2 strains from southern Japan (Itoman and Takanabe). Reciprocal crosses clearly showed that the nondiapause phenotype is inherited in a completely dominant manner, and no maternal effect was detected. Backcrosses to the Itoman and Takanabe strains suggested that dominant nondiapause alleles control the nondiapause phenotype. To clarify the genetic basis of nondiapause in the northern population, we also established a nondiapausing variant ("selected nondiapause" abbreviated as snd) from the Sapporo strain. Crossing experiments revealed that a single recessive allele is responsible for the nondiapause phenotype. Thus, both dominant and recessive inheritance patterns of diapause were detected in the T. urticae populations studied here.

  17. Selective intestinal malabsorption of vitamin B12 displays recessive Mendelian inheritance: Assignment of a locus to chromosome 10 by linkage

    SciTech Connect

    Aminoff, M.; Tahvanainen, E.; Chapelle, A. de la

    1995-10-01

    Juvenile megaloblastic anemia caused by selective intestinal malabsorption of vitamin B12 has been considered a distinct condition displaying autosomal recessive inheritance. It appears to have a worldwide distribution, and comparatively high incidences were reported 30 years ago in Finland and Norway. More recently, the Mendelian inheritance of the condition has been questioned because almost no new cases have occurred in these populations. Here we report linkage studies assigning a recessive-gene locus for the disease to chromosome 10 in previously diagnosed multiplex families from Finland and Norway, proving the Mendelian mode of inheritance. The locus is tentatively assigned to the 6-cM interval between markers D10S548 and D10S466, with a multipoint maximum lod score (Z{sub max}) of 5.36 near marker D10S1477. By haplotype analysis, the healthy sibs in these families did not appear to constitute any examples of nonpenetrance. We hypothesize that the paucity of new cases in these populations is due either to a dietary effect on the gene penetrance that has changed with time, or to a drop in the birth rate in subpopulations showing enrichment of the mutation, or to both of these causes. 38 refs., 4 figs., 2 tabs.

  18. Selective intestinal malabsorption of vitamin B12 displays recessive mendelian inheritance: assignment of a locus to chromosome 10 by linkage.

    PubMed Central

    Aminoff, M; Tahvanainen, E; Gräsbeck, R; Weissenbach, J; Broch, H; de la Chapelle, A

    1995-01-01

    Juvenile megaloblastic anemia caused by selective intestinal malabsorption of vitamin B12 has been considered a distinct condition displaying autosomal recessive inheritance. It appears to have a worldwide distribution, and comparatively high incidences were reported 30 years ago in Finland and Norway. More recently, the Mendelian inheritance of the condition has been questioned because almost no new cases have occurred in these populations. Here we report linkage studies assigning a recessive-gene locus for the disease to chromosome 10 in previously diagnosed multiplex families from Finland and Norway, proving the Mendelian mode of inheritance. The locus is tentatively assigned to the 6-cM interval between markers D10S548 and D10S466, with a multipoint maximum lod score (Zmax) of 5.36 near marker D10S1477. By haplotype analysis, the healthy sibs in these families did not appear to constitute any examples of nonpenetrance. We hypothesize that the paucity of new cases in these populations is due either to a dietary effect on the gene penetrance that has changed with time, or to a drop in the birth rate in subpopulations showing enrichment of the mutation, or to both of these causes. PMID:7573042

  19. Apparent autosomal recessive inheritance in families with proximal spinal muscular atrophy affecting individuals in two generations

    SciTech Connect

    Rudnik-Schoeneborn, S.; Zerres, K.; Hahnen, E.

    1996-11-01

    With the evidence that deletions in the region responsible for childhood- and juvenile-onset proximal spinal muscular atrophy (SMA) are on chromosome 5 it is now possible to confirm autosomal recessive inheritance in most patients (denoted {open_quotes}SMA 5q{close_quotes}). Homozygous deletions in the telomeric copy of the survival motor neuron (SMN) gene can be detected in 95%-98% of patients with early-onset SMA (types I and II), whereas as many as 10%-20% of patients with the milder, juvenile-onset form (type III SMA) do not show deletions. In families with affected subjects in two generations, it is difficult to decide whether they are autosomal dominantly inherited or caused by three independent recessive mutations (pseudodominant inheritance). Given an incidence of >1/10,000 of SMA 5q, patients with autosomal recessive SMA have an {approximately}1% recurrence risk to their offspring. Although the dominant forms are not linked to chromosome 5q, pseudodominant families can now be identified by the presence of homozygous deletions in the SMN gene. 5 refs., 1 fig., 1 tab.

  20. Recessive inheritance of diabetes: the syndrome of diabetes insipidus, diabetes mellitus, optic atrophy and deafness.

    PubMed

    Page, M M; Asmal, A C; Edwards, C R

    1976-07-01

    A few rare syndromes have been delineated in which diabetes mellitus is inherited in association with other conditions. This paper describes five patients, including four siblings in one family, who have diabetes insipidus, diabetes mellitus, optic atrophy and deafness (the DIDMOAD syndrome). The parents of both families are normal but are first cousins. All the patients have insulin-dependent diabetes mellitus with a typical juvenile-onset. The onset of diabetes insipidus was insidious and the symptoms could easily have been ascribed to poor control of diabetes mellitus. The importance of diagnosing diabetes insipidus is that all these patients had dilatation of the urinary tract varying from mild hydroureter to severe hydronephrosis and this improved with treatment of the diabetes insipidus. It is suggested that patients with diabetes mellitus and optic atrophy should have regular screening tests for diabetes insipidus since it is likely that they represent cases of the full syndrome with incomplete clinical expression. The occurrence of this rare syndrome in four siblings of unaffected parents indicates that the syndrome is due to a recessive gene, but the pathogenesis is unknown.

  1. A novel oculo-oto-facial dysplasia in a Native Alaskan community with autosomal recessive inheritance.

    PubMed

    Hing, Anne V; Leblond, Christy; Sze, Raymond W; Starr, Jacqueline R; Monks, Stephanie; Parisi, Melissa A

    2006-04-15

    We describe a novel autosomal recessive malformation syndrome in four related individuals from a geographically isolated Native Alaskan community, who have facial defects similar to those of individuals with Treacher Collins (TCS) and Miller syndrome. Distinctive findings include malar and mandibular hypoplasia, lower eyelid coloboma, choanal atresia, orofacial clefting, and external ear malformation with preauricular tags. Intellect is normal and profound mixed hearing loss has been observed in affected adults. Variable extracranial findings include atrioseptal defect, renal dysplasia, and imperforate anus, however, no limb defects have been observed. Cranial imaging studies demonstrate relative prominence of the zygoma, inferior orbital maxillary hypoplasia, and lateral orbital wall defects with an accessory superior bony projection off the zygoma lateral to the orbital rim. We propose that these individuals have inherited a novel autosomal recessive condition we have termed oculo-oto-facial dysplasia (OOFD) with unique radiographic findings. Copyright 2006 Wiley-Liss, Inc.

  2. Dominant and recessive inheritance of morbid obesity associated with melanocortin 4 receptor deficiency

    PubMed Central

    Farooqi, I. Sadaf; Yeo, Giles S.H.; Keogh, Julia M.; Aminian, Shiva; Jebb, Susan A.; Butler, Gary; Cheetham, Tim; O’Rahilly, Stephen

    2000-01-01

    Over 20 severely obese subjects in 11 independent kindreds have been reported to have pathogenic heterozygous mutations in the gene encoding the melanocortin 4 receptor (MC4R), making this the most common known monogenic cause of human obesity. To date, the detailed clinical phenotype of this dominantly inherited disorder has not been defined, and no homozygous subjects have been described. We determined the nucleotide sequence of the entire coding region of the MC4R gene in 243 subjects with severe, early-onset obesity. A novel two–base pair GT insertion in codon 279 was found in two unrelated subjects, and four novel missense mutations, N62S, R165Q, V253I, C271Y, and one mutation (T112M) reported previously were found in five subjects. N62S was found in homozygous form in five children with severe obesity from a consanguineous pedigree. All four heterozygous carriers were nonobese. Several features of the phenotype, e.g. hyperphagia, tendency toward tall stature, hyperinsulinemia, and preserved reproductive function, closely resemble those reported previously in Mc4r knock-out mice. In addition, a marked increase in bone mineral density was seen in all affected subjects. In transient transfection assays, the N62S mutant receptor showed a responsiveness to αMSH that was intermediate between the wild-type receptor and mutant receptors carrying nonsense and missense mutations associated with dominantly inherited obesity. Thus MC4R mutations result in a syndrome of hyperphagic obesity in humans that can present with either dominant or recessive patterns of inheritance. PMID:10903343

  3. Dominant and recessive inheritance of morbid obesity associated with melanocortin 4 receptor deficiency.

    PubMed

    Farooqi, I S; Yeo, G S; Keogh, J M; Aminian, S; Jebb, S A; Butler, G; Cheetham, T; O'Rahilly, S

    2000-07-01

    Over 20 severely obese subjects in 11 independent kindreds have been reported to have pathogenic heterozygous mutations in the gene encoding the melanocortin 4 receptor (MC4R), making this the most common known monogenic cause of human obesity. To date, the detailed clinical phenotype of this dominantly inherited disorder has not been defined, and no homozygous subjects have been described. We determined the nucleotide sequence of the entire coding region of the MC4R gene in 243 subjects with severe, early-onset obesity. A novel two-base pair GT insertion in codon 279 was found in two unrelated subjects, and four novel missense mutations, N62S, R165Q, V253I, C271Y, and one mutation (T112M) reported previously were found in five subjects. N62S was found in homozygous form in five children with severe obesity from a consanguineous pedigree. All four heterozygous carriers were nonobese. Several features of the phenotype, e.g. hyperphagia, tendency toward tall stature, hyperinsulinemia, and preserved reproductive function, closely resemble those reported previously in Mc4r knock-out mice. In addition, a marked increase in bone mineral density was seen in all affected subjects. In transient transfection assays, the N62S mutant receptor showed a responsiveness to alphaMSH that was intermediate between the wild-type receptor and mutant receptors carrying nonsense and missense mutations associated with dominantly inherited obesity. Thus MC4R mutations result in a syndrome of hyperphagic obesity in humans that can present with either dominant or recessive patterns of inheritance.

  4. Single-locus recessive inheritance of asexual reproduction in a parasitoid wasp.

    PubMed

    Sandrock, Christoph; Vorburger, Christoph

    2011-03-08

    The evolutionary maintenance of sex is one of the big unresolved puzzles in biology. All else being equal, all-female asexual populations should enjoy a two-fold reproductive advantage over sexual relatives consisting of male and female individuals. However, the "all else being equal" assumption rarely holds in real organisms because asexuality tends to be confounded with altered genomic constitutions such as hybridization and polyploidization or to be associated with parthenogenesis-inducing microbes. This limits the ability to draw general conclusions from any particular system. Here we describe a new system that permits unbiased comparisons of sexual and asexual reproduction: the parasitic wasp Lysiphlebus fabarum. Crossing experiments demonstrated that asexual reproduction has a simple genetic basis in this species and is consistently inherited as a single-locus recessive trait. We further show that the asexuality-inducing allele exhibits complete linkage to a specific allele at a microsatellite marker: all asexual lines in the field were homozygous for this allele, and the allele cosegregated perfectly with asexual reproduction in our experimental crossings. This novel system of contagious asexuality allows the production of closely related individuals with different reproductive modes, as well as the monitoring of the asexuality-inducing allele in natural and experimental populations. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Hereditary spastic paraplegias with autosomal dominant, recessive, X-linked, or maternal trait of inheritance.

    PubMed

    Finsterer, Josef; Löscher, Wolfgang; Quasthoff, Stefan; Wanschitz, Julia; Auer-Grumbach, Michaela; Stevanin, Giovanni

    2012-07-15

    Hereditary spastic paraplegia (SPG) is a clinically and genetically heterogeneous group of neurodegenerative disorders that are clinically characterised by progressive spasticity and weakness of the lower-limbs (pure SPG) and, majoritorian, additional more extensive neurological or non-neurological manifestations (complex or complicated SPG). Pure SPG is characterised by progressive spasticity and weakness of the lower-limbs, and occasionally sensory disturbances or bladder dysfunction. Complex SPGs additionally include cognitive impairment, dementia, epilepsy, extrapyramidal disturbances, cerebellar involvement, retinopathy, optic atrophy, deafness, polyneuropathy, or skin lesions in the absence of coexisting disorders. Nineteen SPGs follow an autosomal-dominant (AD-SPG), 27 an autosomal-recessive (AR-SPG), 5 X-linked (XL-SPG), and one a maternal trait of inheritance. SPGs are due to mutations in genes encoding for proteins involved in the maintenance of corticospinal tract neurons. Among the AD-SPGs, 40-45% of patients carry mutations in the SPAST-gene (SPG4) and 10% in the ATL1-gene (SPG3), while the other 9 genes are more rarely involved (NIPA1 (SPG6), KIAA0196 (SPG8), KIF5A (SPG10), RNT2 (SPG12), SPGD1 (SPG13), BSCL2 (SPG17), REEP1 (SPG31), ZFYVE27 (SPG33, debated), and SLC33A1 (SPG42, debated)). Among the AR-SPGs, ~20% of the patients carry mutations in the KIAA1840 (SPG11) gene whereas the 15 other genes are rarely mutated and account for SPGs in single families yet (CYP7B1 (SPG5), SPG7 (SPG7), ZFYVE26 (SPG15), ERLIN2 (SPG18), SPG20 (SPG20), ACP33 (SPG21), KIF1A (SPG30), FA2H (SPG35), NTE (SPG39), GJA12/GJC2 (SPG44), KIAA0415 (SPG48) and 4 genes encoding for the AP4-complex (SPG47)). Among the XL-SPGs, 3 causative genes have been identified (L1CAM (SPG1), PLP1 (SPG2), and SLC16A2 (SPG22)). The diagnosis of SPGs is based on clinical, instrumental and genetic investigations. Treatment is exclusively symptomatic.

  6. A case of non-hallopeau-siemens recessive dystrophic epidermolysis bullosa.

    PubMed

    Kang, Gyo Shin; Ko, Woo Tae; Kim, Jae Hong; Choi, Sung Min; Kim, Ae Suk; Kim, Dong Hoon; Suh, Moo Kyu

    2009-02-01

    Dystrophic epidermolysis bullosa (DEB) is a rare group of heritable mechanobullous disorders that are characterized by blistering and scarring of the skin and mucosae and these lesions are induced by minor trauma, DEB is also associated with nail dystrophy. DEB can be inherited either in an autosomal recessive or dominant fashion. Regardless of the mode of inheritance, DEB is caused by defects of the ultrastructural entity known as the anchoring fibril, which results in separation of the sublamina densa. Recessive DEB (RDEB) is classified into Hallopeau-Siemens and non-Hallopeau-Siemens. We herein report on a case of non-Hallopeau-Siemens RDEB and there was no family history of this malady, and we present the clinical, histological and electron microscopy findings.

  7. Dentinogenesis imperfecta associated with short stature, hearing loss and mental retardation: a new syndrome with autosomal recessive inheritance?

    PubMed

    Cauwels, R G E C; De Coster, P J; Mortier, G R; Marks, L A M; Martens, L C

    2005-08-01

    The follow-up history and oral findings in two brothers from consanguineous parents suggest that the association of dentinogenesis imperfecta (DI), delayed tooth eruption, mild mental retardation, proportionate short stature, sensorineural hearing loss and dysmorphic facies may represent a new syndrome with autosomal recessive inheritance. Histological examination of the dentin matrix of a permanent molar from one of the siblings reveals morphological similarities with defective dentinogenesis as presenting in patients affected with Osteogenesis Imperfecta (OI), a condition caused by deficiency of type I collagen. A number of radiographic and histological characteristics, however, are inconsistent with classical features of DI. These findings suggest that DI may imply greater genetical heterogeneity than currently assumed.

  8. Looking the cow in the eye: deletion in the NID1 gene is associated with recessive inherited cataract in Romagnola cattle.

    PubMed

    Murgiano, Leonardo; Jagannathan, Vidhya; Calderoni, Valerio; Joechler, Monika; Gentile, Arcangelo; Drögemüller, Cord

    2014-01-01

    Cataract is a known condition leading to opacification of the eye lens causing partial or total blindness. Mutations are known to cause autosomal dominant or recessive inherited forms of cataracts in humans, mice, rats, guinea pigs and dogs. The use of large-sized animal models instead of those using mice for the study of this condition has been discussed due to the small size of rodent lenses. Four juvenile-onset cases of bilateral incomplete immature nuclear cataract were recently observed in Romagnola cattle. Pedigree analysis suggested a monogenic autosomal recessive inheritance. In addition to the cataract, one of the cases displayed abnormal head movements. Genome-wide association and homozygosity mapping and subsequent whole genome sequencing of a single case identified two perfectly associated sequence variants in a critical interval of 7.2 Mb on cattle chromosome 28: a missense point mutation located in an uncharacterized locus and an 855 bp deletion across the exon 19/intron 19 border of the bovine nidogen 1 (NID1) gene (c.3579_3604+829del). RT-PCR showed that NID1 is expressed in bovine lenses while the transcript of the second locus was absent. The NID1 deletion leads to the skipping of exon 19 during transcription and is therefore predicted to cause a frameshift and premature stop codon (p.1164fs27X). The truncated protein lacks a C-terminal domain essential for binding with matrix assembly complexes. Nidogen 1 deficient mice show neurological abnormalities and highly irregular crystal lens alterations. This study adds NID1 to the list of candidate genes for inherited cataract in humans and is the first report of a naturally occurring mutation leading to non-syndromic catarct in cattle provides a potential large animal model for human cataract.

  9. Fibrous Tendon Hypertrophy after Gastrocnemius Recession: A Case Report.

    PubMed

    Jastifer, James R; Coughlin, Michael J

    2016-01-01

    Surgical complications after gastrocnemius recession have been rare in published studies. We report a case of symptomatic fibrous tendon hypertrophy requiring revision surgery. Additionally, we have provided a review of the published data on the complications related to this procedure.

  10. Identification of an autosomal recessive mode of inheritance in paediatric Behçet's families by segregation analysis.

    PubMed

    Molinari, N; Koné Paut, I; Manna, R; Demaille, J; Daures, J P; Touitou, I

    2003-10-01

    We have conducted a segregation analysis in order to characterise the transmission of Behçet Disease (BD), a multifactorial condition with a strong genetic component. Complete information about BD status and pedigree was obtained on 104 probands from our database. We used the criteria of the International Study Group for BD (ISBD) to delineate the clinical status of the sibs: possible BD (patients meeting two criteria), or ascertained BD (patients meeting at least three criteria). A proband was defined as "paediatric" when he/she completed ISBD criteria before/by the age of 16 years. Families were distinguished as paediatric (n = 67) (ascertained through a paediatric proband), and non-paediatric (n = 37) ones. An Expectation Maximization (EM) algorithm was used to estimate the Mendelian segregation ratio P in nuclear families (two parents and their offspring). The maximum likelihood estimate: Pcirc; = 0.248, calculated in the paediatric data set, was consistent with the theoretical value of P = (1/4) for autosomal recessive inheritance, whereas the Pcirc; value was 0.08 when using the non-paediatric data set. Our work provides the first evidence of genetic heterogeneity in BD, and of the existence of a Mendelian entity in the paediatric BD subgroup. Previous studies failed to show any simple mode of inheritance in BD, probably because they were performed on the whole BD population.

  11. Development, inheritance and breeding potential of a recessive genic male sterile line D248A in Sesame (Sesamum indicum L.).

    PubMed

    Liu, Hongyan; Yang, Minmin; Wu, Kun; Zhou, Xinan; Zhao, Yingzhong

    2013-01-01

    Genic male sterility (GMS) has great potential for heterosis exploitation in sesame (Sesamum indicum L.). Two spontaneous male-sterile plants were discovered in a Chinese sesame cultivar (Zhuzhi 4) in 2006. By consecutive sib mating with fertile plants from Zhuzhi 4, a new sterile line, D248A, was developed. Anatomy studies showed that D248A has thin, small and greenish anthers on which there are no or little pollen grains. The pollens are irregularly shaped and completely aborted, resulting in no germination and no formation of pollen tubes as revealed by acetocarmine stain or semi-solid suspension culture. Furthermore, D248A has a better performance in growth vigor, bloom duration and yield per plant than the other GMS lines (i.e. 95 ms-2A and 95 ms-5A). To investigate the inheritance mode of fertility, D248A was crossed and backcrossed with six varieties, and a segregating ratio of 3:1 and 1:1 for fertile and sterile plants was observed in F2 and BC1 populations, respectively. These results suggested that D248A is controlled by a recessive GMS gene. The average yield of four D248A-derived F1 hybrids is as high as 1695 kg·ha(-1), which is almost twice of that of 95 ms-5A-derived F1 hybrids. These results indicated that this newly developed recessive GMS line has great potential in sesame hybrid breeding.

  12. Missense SLC25A38 variations play an important role in autosomal recessive inherited sideroblastic anemia.

    PubMed

    Kannengiesser, Caroline; Sanchez, Mayka; Sweeney, Marion; Hetet, Gilles; Kerr, Briedgeen; Moran, Erica; Fuster Soler, Jose L; Maloum, Karim; Matthes, Thomas; Oudot, Caroline; Lascaux, Axelle; Pondarré, Corinne; Sevilla Navarro, Julian; Vidyatilake, Sudharma; Beaumont, Carole; Grandchamp, Bernard; May, Alison

    2011-06-01

    Congenital sideroblastic anemias are rare disorders with several genetic causes; they are characterized by erythroblast mitochondrial iron overload, differ greatly in severity and some occur within a syndrome. The most common cause of non-syndromic, microcytic sideroblastic anemia is a defect in the X-linked 5-aminolevulinate synthase 2 gene but this is not always present. Recently, variations in the gene for the mitochondrial carrier SLC25A38 were reported to cause a non-syndromic, severe type of autosomal-recessive sideroblastic anemia. Further evaluation of the importance of this gene was required to estimate the proportion of patients affected and to gain further insight into the range and types of variations involved. In three European diagnostic laboratories sequence analysis of SLC25A38 was performed on DNA from patients affected by congenital sideroblastic anemia of a non-syndromic nature not caused by variations in the 5-aminolevulinate synthase 2 gene. Eleven patients whose ancestral origins spread across several continents were homozygous or compound heterozygous for ten different SLC25A38 variations causing premature termination of translation (p.Arg117X, p.Tyr109LeufsX43), predicted splicing alteration (c.625G>C; p.Asp209His) or missense substitution (p.Gln56Lys, p.Arg134Cys, p.Ile147Asn, p.Arg187Gln, p.Pro190Arg, p.Gly228Val, p.Arg278Gly). Only three of these variations have been described previously (p.Arg117X, p.Tyr109LeufsX43 and p.Asp209His). All new variants reported here are missense and affect conserved amino acids. Structure modeling suggests that these variants may influence different aspects of transport as described for mutations in other mitochondrial carrier disorders. Mutations in the SLC25A38 gene cause severe, non-syndromic, microcytic/hypochromic sideroblastic anemia in many populations. Missense mutations are shown to be of importance as are mutations that affect protein production. Further investigation of these mutations should

  13. Missense SLC25A38 variations play an important role in autosomal recessive inherited sideroblastic anemia

    PubMed Central

    Kannengiesser, Caroline; Sanchez, Mayka; Sweeney, Marion; Hetet, Gilles; Kerr, Briedgeen; Moran, Erica; Fuster Soler, Jose L.; Maloum, Karim; Matthes, Thomas; Oudot, Caroline; Lascaux, Axelle; Pondarré, Corinne; Sevilla Navarro, Julian; Vidyatilake, Sudharma; Beaumont, Carole; Grandchamp, Bernard; May, Alison

    2011-01-01

    Background Congenital sideroblastic anemias are rare disorders with several genetic causes; they are characterized by erythroblast mitochondrial iron overload, differ greatly in severity and some occur within a syndrome. The most common cause of non-syndromic, microcytic sideroblastic anemia is a defect in the X-linked 5-aminolevulinate synthase 2 gene but this is not always present. Recently, variations in the gene for the mitochondrial carrier SLC25A38 were reported to cause a non-syndromic, severe type of autosomal-recessive sideroblastic anemia. Further evaluation of the importance of this gene was required to estimate the proportion of patients affected and to gain further insight into the range and types of variations involved. Design and Methods In three European diagnostic laboratories sequence analysis of SLC25A38 was performed on DNA from patients affected by congenital sideroblastic anemia of a non-syndromic nature not caused by variations in the 5-aminolevulinate synthase 2 gene. Results Eleven patients whose ancestral origins spread across several continents were homozygous or compound heterozygous for ten different SLC25A38 variations causing premature termination of translation (p.Arg117X, p.Tyr109LeufsX43), predicted splicing alteration (c.625G>C; p.Asp209His) or missense substitution (p.Gln56Lys, p.Arg134Cys, p.Ile147Asn, p.Arg187Gln, p.Pro190Arg, p.Gly228Val, p.Arg278Gly). Only three of these variations have been described previously (p.Arg117X, p.Tyr109LeufsX43 and p.Asp209His). All new variants reported here are missense and affect conserved amino acids. Structure modeling suggests that these variants may influence different aspects of transport as described for mutations in other mitochondrial carrier disorders. Conclusions Mutations in the SLC25A38 gene cause severe, non-syndromic, microcytic/hypochromic sideroblastic anemia in many populations. Missense mutations are shown to be of importance as are mutations that affect protein production

  14. Autosomal recessive Klippel-Feil syndrome

    PubMed Central

    Silva, Elias Oliveira Da

    1982-01-01

    An inbred kindred with 12 cases of Klippel-Feil syndrome (seven females and five males) is reported. Inheritance is undoubtedly autosomal recessive. The main characteristic of the syndrome is fusion of cervical vertebrae. Images PMID:7077623

  15. Autosomal recessive

    MedlinePlus

    ... and the other gene comes from the father. Recessive inheritance means both genes in a pair must be abnormal to cause ... born to parents who carry the same autosomal recessive change ... abnormal gene from both parents and developing the disease. You ...

  16. Two novel cases of compound heterozygous mutations in mitofusin2: Finding out the inheritance.

    PubMed

    Geroldi, Alessandro; Lastella, Patrizia; Patruno, Margherita; Gotta, Fabio; Resta, Nicoletta; Devigili, Grazia; Sabbà, Carlo; Gulli, Rossella; Lamp, Merit; Origone, Paola; Mandich, Paola; Bellone, Emilia

    2017-04-01

    MFN2 is the major gene involved in the axonal form of Charcot-Marie-Tooth disease. It usually has an autosomal dominant pattern of inheritance, but a few cases of homozygous or compound heterozygous mutations have been described. These patients usually present an earlier onset, more severe phenotype and their inheritance pattern can span from autosomal recessive to semidominant. Here we report two unrelated patients carrying two compound heterozygous MFN2 mutations. Both present a pure axonal neuropathy without any additional features. The first patient presents a mild clinical phenotype with onset in the 2nd decade, while the second patient shows a severe, early onset phenotype with loss of independent ambulation. Only a careful clinical examination as well as neurophysiological and genetic studies allowed us to establish the role and the transmission pattern of the identified variants. We discuss practical consequences of this finding in genetic counseling. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Autosomal Recessive Inheritance

    MedlinePlus

    ... visual function, preservation of sight, and the special health problems and requirements of the blind.” News & Events Events Calendar NEI Press Releases News from NEI Grantees Spokesperson bios Statistics and ... Frequently asked questions Clinical Studies Publications Catalog ...

  18. A novel nonsense mutation in keratin 10 causes a familial case of recessive epidermolytic ichthyosis

    PubMed Central

    Gutierrez, Jeydith A; Hannoush, Zeina C; Vargas, Luis G; Momany, Allison; Garcia, Carmen C; Murray, Jeffrey C; Dunnwald, Martine

    2013-01-01

    Epidermolytic ichthyosis (EI) is a rare skin disorder characterized by generalized erythroderma and cutaneous blistering at birth, which is substituted by hyperkeratosis later in life. It is caused by autosomal dominant mutations in highly conserved regions of KRT1 and KRT10. To date, only four mutations with autosomal recessive inheritance of EI have been described in consanguineous families. All of them affect the 2B domain of KRT10. In the present study, we describe four patients with EI (including one lethal case) born from unaffected parents in a consanguineous family of a native Venezuelan community. The objective of this study was to characterize the clinical, genetic, and morphological aspects of the disease in this family, as well as understand its functional implications. Genomic DNA was sequenced for KRT10 and KRT1. Immunofluoresence for keratin expression was performed on cutaneous biopsies. After examination of cutaneous biopsies histology, our results showed hyperkeratosis and acantholysis with an expanded granular layer. Sequencing of KRT10 demonstrated a nonsense mutation (p.Tyr282Ter.) corresponding to the 1B domain of the protein in patients and a heterozygous pattern in other family members, resulting in complete absence of K10. The loss of K10 was compensated by upregulation of K14 and K17. In conclusion, this novel mutation in KRT10 is the first recessive genetic variation that is not located in the so called “hot spot” for recessive EI, suggesting that other areas of the gene are also susceptible for such mutations. PMID:23957016

  19. JS-X syndrome: A multiple congenital malformation with vocal cord paralysis, ear deformity, hearing loss, shoulder musculature underdevelopment, and X-linked recessive inheritance.

    PubMed

    Hoeve, Hans L J; Brooks, Alice S; Smit, Liesbeth S

    2015-07-01

    We report on a family with a not earlier described multiple congenital malformation. Several male family members suffer from laryngeal obstruction caused by bilateral vocal cord paralysis, outer and middle ear deformity with conductive and sensorineural hearing loss, facial dysmorphisms, and underdeveloped shoulder musculature. The affected female members only have middle ear deformity and hearing loss. The pedigree is suggestive of an X-linked recessive inheritance pattern. SNP-array revealed a deletion and duplication on Xq28 in the affected family members. A possible aetiology is a neurocristopathy with most symptoms expressed in structures derived from branchial arches.

  20. Two siblings with early onset fetal akinesia deformation sequence and hydranencephaly: further evidence for autosomal recessive inheritance of hydranencephaly, fowler type.

    PubMed

    Witters, I; Moerman, Ph; Devriendt, K; Braet, P; Van Schoubroeck, D; Van Assche, F A; Fryns, J P

    2002-02-15

    We report a 13-week-old female fetus with early onset fetal akinesia deformation sequence (FADS) and hydranencephaly. In a previous pregnancy, the same ultrasonographic findings were noted at 13 weeks. Fetopathological examination of both female fetuses confirmed FADS with severe arthogryposis, multiple pterygia, and muscular hypoplasia. Neuropathological examination showed massive cystic dilatation of the cerebral ventricles (hydranencephaly) with calcification of the basal ganglion and brain stem and a proliferative vasculopathy throughout the central nervous system. The findings in the two female siblings document the earliest echographic diagnosis of hydranencephaly, Fowler type, and this observation further supports autosomal recessive inheritance of this distinct type of hydranencephaly.

  1. Inheritance of resistance to clopyralid and picloram in yellow starthistle (Centaurea solstitialis L.) is controlled by a single nuclear recessive gene.

    PubMed

    Sabba, R P; Ray, I M; Lownds, N; Sterling, T M

    2003-01-01

    The noxious weed yellow starthistle (Centaurea solstitialis L.) can be controlled effectively at the seedling stage with foliar application of the auxinic herbicides picloram or clopyralid. Although resistance to these herbicides is rare, a yellow starthistle biotype resistant to picloram and cross-resistant to clopyralid was observed in 1989 near Dayton, WA, in a pasture that had been subjected to intensive picloram selective pressure. Our objective was to determine the mode of inheritance for this resistance trait. Transmission of the resistant phenotype was monitored in reciprocal F(1) crosses between susceptible (SCI) and resistant (RDW) plants, their testcross and pseudo-F(2) progeny. Progeny from all crosses, as well as RDW and SCI seedlings of original populations, were sprayed with picloram or clopyralid to distinguish between susceptible and resistant individuals. All F(1) progeny were susceptible to both herbicides, indicating that the resistance trait was of nuclear origin and recessive in nature. Segregation of the resistant phenotype among pseudo-F(2) and testcross progeny of F(1) genotypes demonstrated monofactorial inheritance (P >.25) for resistance to both herbicides. The conclusion that resistance is conferred by a single recessive allele is consistent with the observation that no other picloram-resistant yellow starthistle populations have been identified in the area since picloram selection pressure was abated.

  2. Gingival Recession in a Child-Patient; Easily Missed Etiologies: Case Report with Video

    PubMed Central

    Nwhator, SO

    2014-01-01

    Gingival recession is commonly associated with plaque-induced inflammation and calculus. A high frenal attachment is more important in gingival recession in the child-patient. A healthy child-patient with impeccable oral hygiene presented with localized gingival recession without plaque-induced inflammation which led to the exploration of other possible etiologies. Multiple factors appeared to be acting in consonance (Concomitant multiple etiologies [CME]). The factors were a high frenal attachment, traumatic overbite and bruxism induced by premature tooth contacts. Pedodontists and periodontists should rule out CME in cases of gingival recession in the child-patient. PMID:25031899

  3. Recession curve analysis for groundwater levels: case study in Latvia

    NASA Astrophysics Data System (ADS)

    Gailuma, A.; VÄ«tola, I.; Abramenko, K.; Lauva, D.; Vircavs, V.; Veinbergs, A.; Dimanta, Z.

    2012-04-01

    Recession curve analysis is powerful and effective analysis technique in many research areas related with hydrogeology where observations have to be made, such as water filtration and absorption of moisture, irrigation and drainage, planning of hydroelectric power production and chemical leaching (elution of chemical substances) as well as in other areas. The analysis of the surface runoff hydrograph`s recession curves, which is performed to conceive the after-effects of interaction of precipitation and surface runoff, has approved in practice. The same method for analysis of hydrograph`s recession curves can be applied for the observations of the groundwater levels. There are manually prepared hydrograph for analysis of recession curves for observation wells (MG2, BG2 and AG1) in agricultural monitoring sites in Latvia. Within this study from the available monitoring data of groundwater levels were extracted data of declining periods, splitted by month. The drop-down curves were manually (by changing the date) moved together, until to find the best match, thereby obtaining monthly drop-down curves, representing each month separately. Monthly curves were combined and manually joined, for obtaining characterizing drop-down curves of the year for each well. Within the process of decreased recession curve analysis, from the initial curve was cut out upward areas, leaving only the drops of the curve, consequently, the curve is transformed more closely to the groundwater flow, trying to take out the impact of rain or drought periods from the curve. Respectively, the drop-down curve is part of the data, collected with hydrograph, where data with the discharge dominates, without considering impact of precipitation. Using the recession curve analysis theory, ready tool "A Visual Basic Spreadsheet Macro for Recession Curve Analysis" was used for selection of data and logarithmic functions matching (K. Posavec et.al., GROUND WATER 44, no. 5: 764-767, 2006), as well as

  4. Fragility of the centromeric region of chromosome 1 associated with combined immunodeficiency in siblings. A recessively inherited entity?

    PubMed

    Fasth, A; Forestier, E; Holmberg, E; Holmgren, G; Nordenson, I; Söderström, T; Wahlström, J

    1990-01-01

    Instability of the centromeric region of chromosome 1, and multibranched configurations formed by the short and long arms were seen in a brother and sister with facial dysmorphism, mental retardation and recurrent infections. No chromosomal abnormalities were seen in the parents, who were first cousins. The fragility of chromosome 1 was identified in amniotic fluid cells of the sister. A combined immunodeficiency characterized by a lack of immunoglobulin production, low numbers of T cells and a lack of cells with NK cell markers was diagnosed. This is the first report of familial occurrence of this unique chromosomal aberration. The cause may be an autosomal recessive gene defect.

  5. Erythropoietic protoporphyria in the house mouse. A recessive inherited ferrochelatase deficiency with anemia, photosensitivity, and liver disease.

    PubMed Central

    Tutois, S; Montagutelli, X; Da Silva, V; Jouault, H; Rouyer-Fessard, P; Leroy-Viard, K; Guénet, J L; Nordmann, Y; Beuzard, Y; Deybach, J C

    1991-01-01

    A viable autosomal recessive mutation (named fch, or ferrochelatase deficiency) causing jaundice and anemia in mice arose in a mutagenesis experiment using ethylnitrosourea. Homozygotes (fch/fch) display a hemolytic anemia, photosensitivity, cholestasis, and severe hepatic dysfunction. Protoporphyrin is found at high concentration in erythrocytes, serum, and liver. Ferrochelatase activity in various tissues is 2.7-6.3% of normal. Heterozygotes (+/fch) are not anemic and have normal liver function; they are not sensitive to light exposure; ferrochelatase activity is 45-65% of normal. Southern blot analysis using a ferrochelatase cDNA probe reveals no gross deletion of the ferrochelatase gene. This is the first spontaneous form of erythropoietic protoporphyria in the house mouse. Despite the presence in the mouse of clinical and biochemical features infrequent in the human, this mutation may represent a model for the human disease, especially in its severe form. Images PMID:1939658

  6. Esthetic dentistry for multiple gingival recession cases: Coronally advanced flap with bracket application

    PubMed Central

    Gulati, Minkle; Saini, Ashish; Anand, Vishal; Govila, Vivek

    2016-01-01

    Treatment of gingival recession is essential to rectify the esthetic and functional deficiencies of the patient and to combat further periodontal destruction. However, treating multiple recession cases is quite challenging, and therefore requires constant modifications of the prevalent treatment strategies as per the severity of the condition. The objective of this case report was to evaluate the effectiveness of coronally advanced flap (CAF) technique without vertical incisions using CAF brackets (CAF+B) for treating a patient presenting with class II gingival recession defects in relation to maxillary anteriors. Complete root coverage was observed, and the results were consistent even after 6 months. The current case report demonstrates good outcomes of the CAF + B technique without the use of any additional soft tissue grafts or vertical incisions, therefore, endorsing the promising potential of the CAF + B technique in multiple gingival recession cases. PMID:27143837

  7. Endoscopic gastrocnemius recession: preliminary report on 18 cases.

    PubMed

    Saxena, Amol; Widtfeldt, Arthur

    2004-01-01

    A technique of endoscopic gastrocnemius recession was evaluated. Fifteen patients undergoing 18 procedures were prospectively studied with a minimum follow-up of 1 year. There were 9 women and 6 men (mean age, 44.1 +/- 22.6 years). One patient had an isolated recession; the others had various adjunctive flatfoot or reconstructive procedures. Pre- and postoperative ankle dorsiflexion was evaluated, as was the amount of time before patients could perform a single-leg heel raise postoperatively. The mean preoperative ankle dorsiflexion with the knee extended was -8.7 degrees +/- 3.5 degrees , which improved from a mean 14.9 degrees at 3 months postoperatively to a mean 6.2 degrees +/- 2.6 degrees . At 12 months postoperatively, this value was 3.6 degrees +/- 1.8 degrees , a net postoperative improvement of 12.6 degrees (P < .00001). Patients were able to perform a single-leg heel raise on an average of 13.0 +/- 6.0 weeks. Complications were mostly related to lateral foot dysesthesia in the distribution of the sural nerve (N = 3). Furrowing of the medial leg was noted in 1 patient. No hematomas or neuromas associated with the portal sites were found. These results show endoscopic gastrocnemius recession to be an acceptable method of lengthening the gastrocnemius complex.

  8. Inheritance of skewed X chromosome inactivation in a large family with an X-linked recessive deafness syndrome

    SciTech Connect

    Orstavik, K.H.; Orstavik, R.E.; Eiklid, K.; Tranebjaerg, L.

    1996-07-12

    A new X-linked recessive deafness syndrome was recently reported and mapped to Xq22 (Mohr-Tranebjaeerg syndrome). In addition to deafness, the patients had visual impairment, dystonia, fractures, and mental deterioration. The female carriers did not have any significant manifestations of the syndrome. We examined X chromosome inactivation in 8 obligate and 12 possible carriers by using a polymerase chain reaction analysis of the methylation-dependent amplification of the polymorphic triplet repeat at the androgen receptor locus. Seven of 8 obligate carriers and 1 of 5 carriers by linkage analysis had an extremely skewed pattern in blood DNA not found in 30 normal females. The X inactivation pattern in fibroblast DNA from 2 of the carriers with the extremely skewed pattern was also skewed but to a lesser degree than in blood DNA. One obligate carrier had a random X inactivation pattern in both blood and fibroblast DNA. A selection mechanism for the skewed pattern is therefore not likely. The extremely skewed X inactivation in 8 females of 3 generations in this family may be caused by a single gene that influences skewing of X chromosome inactivation. 22 refs., 2 figs., 1 tab.

  9. Effects of Tip Clearance and Casing Recess on Heat Transfer and Stage Efficiency in Axial Turbines

    NASA Technical Reports Server (NTRS)

    Ameri, A. A.; Steinthorsson, E.; Rigby, David L.

    1998-01-01

    Calculations were performed to assess the effect of the tip leakage flow on the rate of heat transfer to blade, blade tip and casing. The effect on exit angle and efficiency was also examined. Passage geometries with and without casing recess were considered. The geometry and the flow conditions of the GE-E 3 first stage turbine, which represents a modem gas turbine blade were used for the analysis. Clearance heights of 0%, 1%, 1.5% and 3% of the passage height were considered. For the two largest clearance heights considered, different recess depths were studied. There was an increase in the thermal load on all the heat transfer surfaces considered due to enlargement of the clearance gap. Introduction of recessed casing resulted in a drop in the rate of heat transfer on the pressure side but the picture on the suction side was found to be more complex for the smaller tip clearance height considered. For the larger tip clearance height the effect of casing recess was an orderly reduction in the suction side heat transfer as the casing recess height was increased. There was a marked reduction of heat load and peak values on the blade tip upon introduction of casing recess, however only a small reduction was observed on the casing itself. It was reconfirmed that there is a linear relationship between the efficiency and the tip gap height. It was also observed that the recess casing has a small effect on the efficiency but can have a moderating effect on the flow underturning at smaller tip clearances.

  10. Severe Gingival Recession Caused by Traumatic Occlusion and Mucogingival Stress: A Case Report

    PubMed Central

    Ustun, Kemal; Sari, Zafer; Orucoglu, Hasan; Duran, Ismet; Hakki, Sema S.

    2008-01-01

    Gingival recession is displacement of the soft tissue margin apically leading to root surface exposure. Tooth malpositions, high muscle attachment, frenal pull have been associated with gingival tissue recession. Occlusal trauma is defined as injury resulting in tissue changes within the attachment apparatus as a result of occlusal forces. Trauma from occlusion may cause a shift in tooth position and the direction of the movement depends on the occlusal force. We present the clinical and radiological findings and the limitation of periodontal treatment of a severe gingival recession in a case with traumatic occlusion. A 16 years old male, systemically healthy and non-smoking patient presented to our clinic with severe gingival recession of mandibular canines and incisors. Clinical evaluation revealed extensive gingival recession on the vestibules of mandibular anterior segment. Patient has an Angle class III malocclusion and deep bite. To maintain the teeth until orthodontic therapy and maxillofacial surgery, mucogingival surgeries were performed to obtain attached gingiva to provide oral hygiene and reduce inflammation. After mucogingival surgeries, limited attached gingiva was gained in this case. Regular periodontal maintenance therapy was performed at 2 month intervals to preserve mandibular anterior teeth. Multidisciplinary approach should be performed in this kind of case for satisfactory results. Unless occlusal relationship was corrected, treatment of severe gingival recession will be problematic. For satisfactory periodontal treatment, early diagnosis of trauma from occlusion and its treatment is very important. PMID:19212523

  11. Severe gingival recession caused by traumatic occlusion and mucogingival stress: a case report.

    PubMed

    Ustun, Kemal; Sari, Zafer; Orucoglu, Hasan; Duran, Ismet; Hakki, Sema S

    2008-04-01

    Gingival recession is displacement of the soft tissue margin apically leading to root surface exposure. Tooth malpositions, high muscle attachment, frenal pull have been associated with gingival tissue recession. Occlusal trauma is defined as injury resulting in tissue changes within the attachment apparatus as a result of occlusal forces. Trauma from occlusion may cause a shift in tooth position and the direction of the movement depends on the occlusal force. We present the clinical and radiological findings and the limitation of periodontal treatment of a severe gingival recession in a case with traumatic occlusion. A 16 years old male, systemically healthy and non-smoking patient presented to our clinic with severe gingival recession of mandibular canines and incisors. Clinical evaluation revealed extensive gingival recession on the vestibules of mandibular anterior segment. Patient has an Angle class III malocclusion and deep bite. To maintain the teeth until orthodontic therapy and maxillofacial surgery, mucogingival surgeries were performed to obtain attached gingiva to provide oral hygiene and reduce inflammation. After mucogingival surgeries, limited attached gingiva was gained in this case. Regular periodontal maintenance therapy was performed at 2 month intervals to preserve mandibular anterior teeth. Multidisciplinary approach should be performed in this kind of case for satisfactory results. Unless occlusal relationship was corrected, treatment of severe gingival recession will be problematic. For satisfactory periodontal treatment, early diagnosis of trauma from occlusion and its treatment is very important.

  12. Management of Gingival Recession Associated with Orthodontic Treatment: A Case Report

    PubMed Central

    Rana, Tarun Kumar; Sharma, Tarun; Prasad, Narayana; Singh, Shailendra

    2014-01-01

    Many patients undergo orthodontic treatment for aesthetic improvement. It is well established that the patients who undergo orthodontic treatment have a high susceptibility to present plaque accumulation on their teeth because of the presence of brackets, wires and/or other orthodontic elements on the teeth surfaces with which the oral hygiene procedures might be more difficult. The orthodontic treatment is a double-action procedure regarding the periodontal tissues which may be very meaningful in increasing the periodontal health status and may be a harmful procedure which can be followed by several types of periodontal complications. There is a strong correlation between the severity and extent of gingival recessions and the orthodontic treatment suggesting that orthodontic tooth movement may lead to gingival recession. The principal objective in the treatment of gingival recession is to cover the exposed root surfaces to improve aesthetics and to reduce hypersensitivity. Different soft tissue grafting procedures have been proposed in the treatment of gingival recessions. Subepithelial connective tissue graft is a reliable method for treatment of gingival recession. The purpose of this case report was to illustrate the relationship between orthodontic therapy and gingival recession and to describe the management of this case. PMID:25177647

  13. [Evidence for autosomal dominant inheritance through the maternal line in a case of primary ciliary diskinesia].

    PubMed

    Alvarez González, J; Busto Castañón, L; Nistal Serrano, M

    2006-01-01

    An atypical case of primary ciliary dyskinesia is presented in which the inheritance, rather than the classical autosomal recessive, appears to be transmitted as an autosomal dominant trait through the maternal line. The case involves two brothers of 29 and 30 years of age, married without children, with a history of infertility, frequent episodes of sinusitis, and recurrent pulmonary infections. Their mother and sister have chronic bronchopathy of unknown etiology. Their father is healthy without pulmonary problems or sinusitis. At physical exam, both brothers, sister and mother presented with bronchial rhonchi at lung auscultation. Blood analysis and pulmonary function, liver and renal tests were all normal. The ultraestructual study of the sperm flagellum by electron microscopy revealed that both brothers have the same anomaly. Namely, in the majority of the cross-sections, both dynein arms are missing. The nexin filament was present, as well as the radial spokes and the central pair of microtubules. In some sperm, besides the absence of dynein arms, there was also absence of the central pair of microtubules. Neither anomalies of the fibrous sheath nor of the dense fibers were found. In approximately 50% of the spermatozoa, the midpiece had a decreased number of mitochondria and extra non-aligned mitochondria. Other findings included extra peripheral microtubules in the axoneme.

  14. Inheritance and testicular cancer.

    PubMed Central

    Nicholson, P. W.; Harland, S. J.

    1995-01-01

    Statistical analysis of published data on the age of onset of germ cell tumours of the testis and of the prevalence of bilateral disease in familial and general cases suggest the following: 1. Patients with bilateral disease carry the same genetic predisposition as familial cases. 2. Males with the hereditary predisposition develop none, unilateral or bilateral tumours in the proportions 55%, 38% and 7% respectively. 3. One-third of all testis cancer patients are genetically predisposed to the disease. 4. The 2.2% risk to brothers of cases as reported elsewhere can be accounted for by the homozygous (recessive) inheritance of a single predisposing gene. PMID:7841065

  15. Autosomal recessive cerebellar ataxias

    PubMed Central

    Palau, Francesc; Espinós, Carmen

    2006-01-01

    Autosomal recessive cerebellar ataxias (ARCA) are a heterogeneous group of rare neurological disorders involving both central and peripheral nervous system, and in some case other systems and organs, and characterized by degeneration or abnormal development of cerebellum and spinal cord, autosomal recessive inheritance and, in most cases, early onset occurring before the age of 20 years. This group encompasses a large number of rare diseases, the most frequent in Caucasian population being Friedreich ataxia (estimated prevalence 2–4/100,000), ataxia-telangiectasia (1–2.5/100,000) and early onset cerebellar ataxia with retained tendon reflexes (1/100,000). Other forms ARCA are much less common. Based on clinicogenetic criteria, five main types ARCA can be distinguished: congenital ataxias (developmental disorder), ataxias associated with metabolic disorders, ataxias with a DNA repair defect, degenerative ataxias, and ataxia associated with other features. These diseases are due to mutations in specific genes, some of which have been identified, such as frataxin in Friedreich ataxia, α-tocopherol transfer protein in ataxia with vitamin E deficiency (AVED), aprataxin in ataxia with oculomotor apraxia (AOA1), and senataxin in ataxia with oculomotor apraxia (AOA2). Clinical diagnosis is confirmed by ancillary tests such as neuroimaging (magnetic resonance imaging, scanning), electrophysiological examination, and mutation analysis when the causative gene is identified. Correct clinical and genetic diagnosis is important for appropriate genetic counseling and prognosis and, in some instances, pharmacological treatment. Due to autosomal recessive inheritance, previous familial history of affected individuals is unlikely. For most ARCA there is no specific drug treatment except for coenzyme Q10 deficiency and abetalipoproteinemia. PMID:17112370

  16. Semilunar vestibular technique: A novel procedure for multiple recession coverage (a report of two cases)

    PubMed Central

    Pandit, Nymphea; Pandit, Inder Kumar; Bali, Deepika; Jindal, Shaifi

    2015-01-01

    The procedures for root coverage have been greatly refined over the past few decades. Still as compared to the other periodontal surgical procedures, predictability of mucogingival procedures remains uncertain which is more in patients who present with multiple recessions or recession complicated with periodontal involvement. Techniques which claim success almost always involve a second surgical site. A novel technique avoiding second surgical site and good predictability for multiple recessions was described by Dr. P.D. Miller in a conference at Pune in 2011. A semilunar vestibular incision technique described by Dr. P.D Miller was performed on two patients who presented with multiple recessions in the maxillary anterior teeth. About 90–100% root coverage was observed when the patients were on a follow-up for 1-year with a significant increase in the vestibular depth. The semilunar vestibular incision technique used in two cases resulted in predictable root coverage with a good color blend, an esthetic marginal morphology and most importantly the avoidance of the second surgical site. PMID:26941524

  17. Localized gingival recession caused by a C-PAP mask: a case report.

    PubMed

    Mason, William E

    2002-10-01

    This case report describes a localized gingival recession on the labial of tooth # 6 caused by the nasal mask of a C-PAP (Continuous Positive Air Pressure) machine. The patient was diagnosed with obstructive sleep apnea (OSA). Treatment consisted of night-time use of a C-PAP machine. The patient noticed sudden exposure of the root surface on no. 6 and sought evaluation by his family dentist. He was referred to a periodontist for evaluation. A subepithelial connective tissue graft was performed to repair the defect. A maxillary bite splint with a buccal and apical extension to protect the grafted area was constructed. The patient is able to wear the C-PAP mask and protective splint concurrently for successful treatment of his OSA and maintenance of the newly grafted connective tissue. We as dental practitioners can use this information to evaluate the etiology of gingival recession, especially those occurring in patients with OSA.

  18. Treatment of gingival recession using enamel matrix proteins: a case report with 4-year follow-up.

    PubMed

    Kuru, Bahar; Yilmaz, Selçuk; Noyan, Ulkü

    2007-05-01

    Obtaining predictable and optimal coverage of exposed root surfaces and correction of corresponding gingival recessions have become important goals of periodontal plastic surgery. Various surgical techniques have been proposed for coverage of root surfaces. A therapeutic advantage may be gained if periodontal regeneration is obtained in addition to coverage of root with gingiva. In this case report, surgical recession coverage was performed as the bilaterally pedicled lateral sliding flap technique with the adjunctive use of enamel matrix derivative bioactive material (Emdogain). A female patient with gingival recession on maxillary central incisors is presented with 4-year follow-up observation. The surgical procedure used in this clinical pilot case study produced a marked reduction in gingival recession that was maintained for 4 years. Initial gingival recession averaged 4.25 mm with a probing depth of 1.25 mm. The 4-year follow-up demonstrated no significant changes in the degree of postoperative results obtained after 1 year. At the 4-year follow-up, a mean of 3.75 mm of root coverage was observed (93.8% root coverage). Probing depth averaged 0.75 mm, indicating a total of 4.25 mm gain of clinical attachment. Within the limits of this case, the results demonstrated the possibility of treating human buccal recessions by means of enamel matrix protein derivative together with the laterally repositioned flap technique, with a predictable reduction in recession and clinical gain in attachment.

  19. Recessive thrombocytopenia likely due to a homozygous pathogenic variant in the FYB gene: case report.

    PubMed

    Hamamy, Hanan; Makrythanasis, Periklis; Al-Allawi, Nasir; Muhsin, Abdulrahman A; Antonarakis, Stylianos E

    2014-12-17

    Inherited thrombocytopenias (IT) are a heterogeneous group of rare diseases characterized by a reduced number of blood platelets. The frequency of IT is probably underestimated because of diagnostic difficulties and because not all the existing forms have as yet been identified, with some patients remaining without a definitive diagnosis. Exome Sequencing has made possible the identification of almost all variants in the coding regions of protein-coding genes, thereby providing the opportunity to identify the disease causing gene in a number of patients with indefinite diagnoses, specifically in consanguineous families. Familial thrombocytopenia with small size platelets was present in several members of a highly consanguineous family from Northern Iraq. Genotyping of all affected, their unaffected siblings and parents, followed by exome sequencing revealed a strong candidate loss of function variant in a homozygous state: a frameshift mutation in the FYB gene. The protein encoded by this gene is known to be a cytosolic adaptor molecule expressed by T, natural killer (NK), myeloid cells and platelets, and is involved in platelet activation and controls the expression of interleukin-2. Knock-out mice were reported to show isolated thrombocytopenia. Inherited thrombocytopenias differ in their presentation, associated features, and molecular etiologies. An accurate diagnosis is needed to provide appropriate management as well as counseling for the individuals and their family members. Exome sequencing may become a first diagnostic tool to identify the molecular basis of undiagnosed familial IT. In this report, the clinical evaluation combined with the power and efficiency of genomic analysis defined the FYB gene as the possible underlying cause of autosomal recessive thrombocytopenia with small platelet size. This is the first report linking pathogenic variants in FYB and thrombocytopenia in humans.

  20. Guided Tissue Regeneration Involving Piercing-Induced Lingual Recession: A Case Report.

    PubMed

    Parra, Carlos; Jeong, Y Natalie; Hawley, Charles E

    Recession on the lingual aspect of mandibular incisors may occur in patients with history of tongue piercing and other factitious traumatic habits. Treatment of these areas is challenging due to the site-specific anatomical features of the region. This case report presents a novel approach for a specific type of mandibular lingual defect caused by tongue piercing. A nonresorbable titanium-reinforced barrier membrane combined with an allograft and enamel matrix derivatives was used to promote regeneration of periodontal attachment. Reentry surgery for membrane removal was performed at 8 weeks. The time from initial surgery to final follow-up was 18 months.

  1. A case of rare recessive oculopharyngeal muscular dystrophy (OPMD) coexisting with hereditary neuropathy with liability to pressure palsies (HNPP).

    PubMed

    Marsh, Eleanor A; Robinson, David O

    2008-05-01

    Oculopharyngeal muscular dystrophy (OPMD) is typically inherited in an autosomal dominant fashion and is characterized by late onset proximal muscle weakness, ptosis and difficulty swallowing. It is caused by expansion mutations in the PABPN1 gene on chromosome 14q11. There is also a rare recessive form of the disease caused by homozygosity of a very small expansion mutation in the same gene. Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder characterized by recurrent peripheral monofocal neuropathies. In this report a patient with both recessive OPMD and HNPP is described. The presence of two genetically unlinked neurological diagnoses in the same individual is a rare event and may have delayed the diagnoses.

  2. Periodontal and Restorative Treatment of Gingival Recession Associated with Non-Carious Cervical Lesions: Case Study.

    PubMed

    Pereira, Analice Giovani; Teixeira, Daniela Navarro Ribeiro; Soares, Michelle Pereira Costa Mundim; Gonzaga, Ramon Corrêa de Queiroz; Fernandes-Neto, Alfredo Júlio; Soares, Paulo Vinícius

    2016-01-14

    The association between the presence of gingival recession and non-carious cervical lesions is a common finding in dentistry. These diseases have multifactorial etiology and the treatment should be multidisciplinary. Although traditionally the majority of professionals treat non-carious cervical lesions only with conventional restorative procedures, in most cases a combination of periodontal and restorative treatments provides the best functional and esthetic results. Thus, the objective of this case report was to present a new option for treatment, which consists of a subepithelial connective tissue graft associated with a coronally advanced flap placed on dentin and non-carious cervical lesions restored with lithium disilicate partial veneers. A patient complaining about the esthetic aspects of her teeth and cervical dentin hypersensitivity was submitted to occlusal adjustments and daily diet analysis in order to manage etiologic factors. Experienced operators then performed restorative and surgical treatments. Periodontal clinical attachment level (probing depth + gingival margin), bleeding on probing, plaque index, and the integrity of the restorations were observed. During the monitoring period, the treatment was effective, with good functional and esthetic results. The hypersensitivity disappeared, and neither inflammatory characteristics in gingival tissue nor failures in restorations were noted. It might be concluded that treatment with a combination of techniques can be effective and predictable for patients with gingival recession and non-carious cervical lesions that may or may not require restorative procedures under controlled conditions. Copyright© by the International Academy of Periodontology.

  3. Unilateral Autosomal Recessive Anophthalmia in a Patient with Cystic Craniopharyngioma

    PubMed Central

    Kumar, Amandeep; Bansal, Ankit; Garg, Ajay; Sharma, Bhawani S.

    2014-01-01

    Abstract Anophthalmia is a rare ocular malformation. It is a genetically determined disorder and is typically associated with syndromes. However, sporadic nonsyndromic familial as well as non-familial cases of anophthalmia have also been reported. Non-syndromic familial cases are usually bilateral and have been attributed to autosomal recessive, autosomal dominant, and X-linked inheritance patterns. The authors hereby report a rare case of autosomal recessive unilateral anophthalmia in a patient with no other associated congenital anomaly. Patient was operated for craniopharyngioma. The clinical, radiological and intraoperative findings are discussed. PMID:27928292

  4. Treatment of localized gingival recessions using enamel matrix derivative as an adjunct to laterally sliding flap: 2 case reports.

    PubMed

    Kuru, Bahar Eren

    2009-06-01

    Predictable and optimal coverage of exposed root surfaces is an important goal in periodontal plastic surgery. In this report, recession coverage was performed as laterally sliding flap technique with the adjunctive use of enamel matrix derivative (EMD). The cases of 2 female patients with gingival recession on the maxillary canines are presented with 1-year follow-up observation. Initial vertical gingival recessions were 4.0 mm each, with a probing depth of 1.0 mm. The surgical procedure immediately produced a marked reduction in gingival recessions. In the course of healing, the soft tissue margin on the operated teeth showed some shrinkage in the first months. After 1 year, complete root coverage (100%) was observed, with a probing depth of 0.5 mm and 5.0-mm gain of clinical attachment in both cases, and there was 0.5-mm creeping tissue above the cemento-enamel junction. Within the limits of these cases, the results demonstrated the possibility of treating human buccal recessions with EMD plus laterally sliding flap, with predictable root coverage and clinical attachment gain.

  5. Recessive and Dominant Mutations in Retinoic Acid Receptor Beta in Cases with Microphthalmia and Diaphragmatic Hernia

    PubMed Central

    Srour, Myriam; Chitayat, David; Caron, Véronique; Chassaing, Nicolas; Bitoun, Pierre; Patry, Lysanne; Cordier, Marie-Pierre; Capo-Chichi, José-Mario; Francannet, Christine; Calvas, Patrick; Ragge, Nicola; Dobrzeniecka, Sylvia; Hamdan, Fadi F.; Rouleau, Guy A.; Tremblay, André; Michaud, Jacques L.

    2013-01-01

    Anophthalmia and/or microphthalmia, pulmonary hypoplasia, diaphragmatic hernia, and cardiac defects are the main features of PDAC syndrome. Recessive mutations in STRA6, encoding a membrane receptor for the retinol-binding protein, have been identified in some cases with PDAC syndrome, although many cases have remained unexplained. Using whole-exome sequencing, we found that two PDAC-syndrome-affected siblings, but not their unaffected sibling, were compound heterozygous for nonsense (c.355C>T [p.Arg119∗]) and frameshift (c.1201_1202insCT [p.Ile403Serfs∗15]) mutations in retinoic acid receptor beta (RARB). Transfection studies showed that p.Arg119∗ and p.Ile403Serfs∗15 altered RARB had no transcriptional activity in response to ligands, confirming that the mutations induced a loss of function. We then sequenced RARB in 15 subjects with anophthalmia and/or microphthalmia and at least one other feature of PDAC syndrome. Surprisingly, three unrelated subjects with microphthalmia and diaphragmatic hernia showed de novo missense mutations affecting the same codon; two of the subjects had the c.1159C>T (Arg387Cys) mutation, whereas the other one carried the c.1159C>A (p.Arg387Ser) mutation. We found that compared to the wild-type receptor, p.Arg387Ser and p.Arg387Cys altered RARB induced a 2- to 3-fold increase in transcriptional activity in response to retinoic acid ligands, suggesting a gain-of-function mechanism. Our study thus suggests that both recessive and dominant mutations in RARB cause anophthalmia and/or microphthalmia and diaphragmatic hernia, providing further evidence of the crucial role of the retinoic acid pathway during eye development and organogenesis. PMID:24075189

  6. Dropped-head in recessive oculopharyngeal muscular dystrophy.

    PubMed

    Garibaldi, Matteo; Pennisi, Elena Maria; Bruttini, Mirella; Bizzarri, Veronica; Bucci, Elisabetta; Morino, Stefania; Talerico, Caterina; Stoppacciaro, Antonella; Renieri, Alessandra; Antonini, Giovanni

    2015-11-01

    A 69-year-old woman presented a dropped head, caused by severe neck extensor weakness that had started two years before. She had also developed a mild degree of dysphagia, rhinolalia, eyelid ptosis and proximal limb weakness during the last months. EMG revealed myopathic changes. Muscle MRI detected fatty infiltration in the posterior neck muscles and tongue. Muscle biopsy revealed fiber size variations, sporadic rimmed vacuoles, small scattered angulated fibers and a patchy myofibrillar network. Genetic analysis revealed homozygous (GCN)11 expansions in the PABPN1 gene that were consistent with recessive oculopharyngeal muscular dystrophy (OPMD). There are a few reports of the recessive form, which has a later disease onset with milder symptoms and higher clinical variability than the typical dominantly inherited form. This patient, who is the first Italian and the eighth worldwide reported case of recessive OPMD, is also the first case of OPMD with dropped-head syndrome, which thus expands the clinical phenotype of recessive OPMD.

  7. A Case Study of Teachers' Recess Practices Related to Students with Exceptional Learning Needs

    ERIC Educational Resources Information Center

    Campbell, Andrea E.

    2012-01-01

    Appropriate recess time for young students is an agent for healthy growth, development, and academic performance. Recess time for young students is dissipating due to increased pressure for higher test scores, problematic behaviors on the playground, and its inclusion within classroom discipline policies. Researchers have reported the majority…

  8. A Case Study of Teachers' Recess Practices Related to Students with Exceptional Learning Needs

    ERIC Educational Resources Information Center

    Campbell, Andrea E.

    2012-01-01

    Appropriate recess time for young students is an agent for healthy growth, development, and academic performance. Recess time for young students is dissipating due to increased pressure for higher test scores, problematic behaviors on the playground, and its inclusion within classroom discipline policies. Researchers have reported the majority…

  9. Olfactory epithelium in the olfactory recess: a case study in new world leaf-nosed bats.

    PubMed

    Eiting, Thomas P; Smith, Timothy D; Dumont, Elizabeth R

    2014-11-01

    The olfactory recess (OR) is a restricted space at the back of the nasal fossa in many mammals that is thought to improve olfactory function. Mammals that have an olfactory recess are usually described as keen-scented, while those that do not are typically thought of as less reliant on olfaction. However, the presence of an olfactory recess is not a binary trait. Many mammal families have members that vary substantially in the size and complexity of the olfactory recess. There is also variation in the amount of olfactory epithelium (OE) that is housed in the olfactory recess. Among New World leaf-nosed bats (family Phyllostomidae), species vary by over an order of magnitude in how much of their total OE lies within the OR. Does this variation relate to previously documented neuroanatomical proxies for olfactory reliance? Using data from 12 species of phyllostomid bats, we addressed the hypothesis that the amount of OE within the OR relates to a species' dependence on olfaction, as measured by two commonly used neuroanatomical metrics, the size of the olfactory bulb, and the number of glomeruli in the olfactory bulb, which are the first processing units within the olfactory signal cascade. We found that the percentage of OE within the OR does not relate to either measure of olfactory "ability." This suggests that olfactory reliance is not reflected in the size of the olfactory recess. We explore other roles that the olfactory recess may play. © 2014 Wiley Periodicals, Inc.

  10. A rare case of respiratory disorders associated with two autosomal recessive diseases and male infertility

    PubMed Central

    Costa, Sergio López; Scigliano, Sergio; Menga, Guillermo; Demiceu, Sergio; Palaoro, Luis Alberto

    2013-01-01

    The study of nasal ciliary beat frequency (CBF) and ultrastructure may contribute to the understanding of pathognomonic cases of male infertility associated with defects in sperm motility. This study was designed to report a particular case of male infertility, characterized by the association of two respiratory autosomal recessive genetic diseases (alpha-1-antitrypsin deficiency [AAT-D] and primary ciliary dyskinesia [PCD]). A 39-year-old patient with complete sperm immotility, AAT-D, and bronchiectasis was studied in the Laboratory of Male Fertility, the Department of Urology, the Respiratory Center of a Pediatric Hospital, and in the Department of Clinical Medicine of a Rehabilitation Respiratory Hospital. Family history, physical examination, hormonal analysis, microbial assays, semen analysis, nasal ciliary function, and structure study by digital high-speed video photography and transmission electron microscopy are described. A noninvasive nasal biopsy to retrieve ciliated epithelium lining the inferior surface of the inferior nasal turbinates was performed and CBF was determined. Beat pattern was slightly curved and rigid, not wide, and metacronic in all the observed fields analyzed. CBF was 8.2 Hz in average (reference value, 10–15 Hz) Ultrastructural assay revealed absence of the inner dynein arms in 97% of the cilia observed. The final infertility accurate diagnosis was achieved by the study of nasal CBF and ultrastructure contributing to the patient health management and genetic counseling while deciding fatherhood. Beyond this particular case, the present report may open a new field of studies in male infertility, mainly in cases of asthenozoospermia. PMID:23772318

  11. Boucher Neuhäuser Syndrome - A rare cause of inherited hypogonadotropic hypogonadism. A case of two adult siblings with two novel mutations in PNPLA6.

    PubMed

    Langdahl, Jakob H; Frederiksen, Anja L; Nguyen, Nina; Brusgaard, Klaus; Juhl, Claus B

    2017-02-01

    Boucher Neuhäuser Syndrome (BNS) is a rare clinical syndrome with autosomal recessive inheritance defined by early-onset ataxia, hypogonadism and chorioretinal dystrophy. We present two siblings diagnosed with BNS in late adult life identified with compound heterozygous state of two novel PNPLA6 mutations. Five healthy siblings were non- or heterozygous carriers of the mutations. The cases, which presented with ataxia in childhood and hypogonadotropic hypogonadism (HH), were diagnosed at age 17 and 25, respectively, when examined for delayed puberty. The youngest case, a 55-year old male, was referred to our department in 2006 for evaluation of secondary causes of osteoporosis, which he developed despite adequate testosterone replacement therapy. The unusual medical history with childhood ataxia and hypogonadotropic hypogonadism lead to further examinations and eventually the diagnosis of BNS. The older sister of the proband also displayed the triad of ataxia, HH and chorioretinal dystrophy accompanied by cerebellar atrophy and in 2014, we found the mutations in PNPLA6. BNS is a rare cause of HH and secondary osteoporosis, but should be considered in patients presenting with one or more of the key features. Genetic screening is becoming increasingly available and inexpensive and accordingly this may be considered earlier and by broader indication in unusual phenotypic presentations. The increasing knowledge of causes for inherited diseases should extend the use of genetic screening, as the correct diagnosis will benefit the patients.

  12. Pupil abnormalities in 131 cases of genetically defined inherited peripheral neuropathy.

    PubMed

    Houlden, H; Reilly, M M; Smith, S

    2009-04-01

    To investigate and correlate the frequency and types of pupil abnormalities that are associated with hereditary peripheral neuropathy in a large cohort of patients prospectively examined. A prospective study between 1998 and 2007. Patients were enrolled and examined after being seen in the neurology clinic. Data were collected on demographics, family and medical history. Patients had eye and pupillography testing carried out as well as being neurologically and genetically investigated. A consecutive series of 131 cases of inherited peripheral neuropathy were seen and categorized into five groups: familial amyloid polyneuropathy (FAP), Charcot Marie Tooth disease (CMT), hereditary neuropathywith liability to pressure palsies (HNPP), Refsum's disease, and hereditary sensory and autonomic neuropathy. A number of unreported mutations were identified in these patient groups. Pupil abnormalities were common in the Refsum's group, with frequent abnormally small pupils. The inherited neuropathies commonly associated with autonomic abnormalities were frequently found to have developed bilateral Horner's syndrome, which was particularly prevalent in our FAP series. Abnormalities were rare in HNPP and CMT type 1, but CMT type 2 showed frequent and varied pupil defects. The results describe the pupil abnormalities that were frequently associated with the particular group of inherited neuropathy patients, but we could not predict the genetic defect or the neuropathy severity. This is the first study of the pupil abnormalities found in the inherited neuropathies and provides an overview of the frequency and type of defects seen in a large number of cases. This series along with the detailed tables will act as an important diagnostic aid in assessing these patients.

  13. Evaluation of a Mitochondrial DNA Mutation in Maternally Inherited and Sporadic Cases of Dupuytren Disease

    PubMed Central

    Anderson, Eric R.; Burmester, James K.; Caldwell, Michael D.

    2012-01-01

    Objective The purpose was to test the hypothesis that Dupuytren disease (DD) is associated with a previously reported mutation in mitochondrial DNA at position 2839. Methods Two hundred sixty-nine cases of DD and an equal number of matched controls were identified in Marshfield Clinic’s Personalized Medicine Research Project (PMRP). Clinical data used to describe the cohort were abstracted from the electronic medical records of the population. Genetic analysis of all the cases and controls was done using a custom synthesis TaqMan assay, while genetic analysis of sixteen of the above cases with a familial history of DD was performed by mitochondrial DNA sequencing at position C2839A. Results Cases and controls were evenly distributed with 167 (62%) men and 102 (38%) women. The majority, 264 (98%) of the cases and controls were white non-Hispanic. Of the 269 cases, 16 were found to have a familial history of DD. Two cases had a maternal history, eight a paternal history, five an affected sibling, and one a paternal grandfather. All cases and controls were found to have only the C allele at the site of the reported mitochondrial C2839A polymorphism. Conclusions The previously reported mitochondrial mutation was not present in our small, maternally inherited cohort or in the total population of 538 cases and controls. This finding does not support the reported incidence of this polymorphism in 90% of the affected population with a maternal inheritance, and calls into question the role of the C2839A mitochondrial DNA polymorphism in familial or sporadic cases of DD. PMID:22634541

  14. Inherited Neuropathies

    PubMed Central

    Li, Jun

    2013-01-01

    With a prevalence of 1 in 2500 people, inherited peripheral nerve diseases, collectively called Charcot-Marie-Tooth disease (CMT), are among the most common inherited neurologic disorders. Patients with CMT typically present with chronic muscle weakness and atrophy in limbs, sensory loss in the feet and hands, and foot deformities. Clinical similarities between patients often require genetic testing to achieve a precise diagnosis. In this article, the author reviews the clinical and pathologic features of CMT, and demonstrates how electrodiagnostic and genetic tools are used to assist in the diagnosis and symptomatic management of the diseases. Several cases are presented to illustrate the diagnostic processes. PMID:23117945

  15. As little as needed: the extraordinary case of a mild recessive osteopetrosis owing to a novel splicing hypomorphic mutation in the TCIRG1 gene.

    PubMed

    Sobacchi, Cristina; Pangrazio, Alessandra; Lopez, Antonio González-Meneses; Gomez, Diego Pascual-Vaca; Caldana, Maria Elena; Susani, Lucia; Vezzoni, Paolo; Villa, Anna

    2014-07-01

    Mutations in the TCIRG1 gene, coding for a subunit of the osteoclast proton pump, are responsible for more than 50% of cases of human malignant autosomal recessive osteopetrosis (ARO), a rare inherited bone disease with increased bone density owing to a failure in bone resorption. A wide variety of mutations has been described, including missense, nonsense, small deletions/insertions, splice-site mutations, and large genomic deletions, all leading to a similar severe presentation. So far, to the best of our knowledge, no report of a mild phenotype owing to recessive TCIRG1 mutations is present neither in our series of more than 100 TCIRG1-dependent ARO patients nor in the literature. Here we describe an 8-year-old patient referred to us with a clinical diagnosis of ARO, based on radiological findings; of note, no neurological or hematological defects were present in this girl. Surprisingly, we identified a novel nucleotide change in intron 15 of the TCIRG1 gene at the homozygous state, leading to the production of multiple aberrant transcripts, but also, more importantly, of a limited amount of the normal transcript. Our results show that a low level of normal TCIRG1 protein can dampen the clinical presentation of TCIRG1-dependent ARO. On this basis, a small amount of protein might be sufficient to rescue, at least partially, the severe ARO phenotype, and this is particularly important when gene therapy approaches are considered. In addition, we would also recommend that the TCIRG1 gene be included in the molecular diagnosis of mild forms of human ARO.

  16. Morbidity associated with high gastrocnemius recession: retrospective review of 126 cases.

    PubMed

    Rush, Shannon M; Ford, Lawrence A; Hamilton, Graham A

    2006-01-01

    To evaluate morbidity associated with surgical lengthening of the gastrocnemius, medical records were reviewed retrospectively for 126 patients (mean age, 49.7 years; range, 8-78 years) who had undergone open gastrocnemius recession. Ten patients had isolated recession; 116 had gastrocnemius recession with an additional foot or ankle procedure on the ipsilateral limb. During a mean follow-up period of 19 months (range, 6-50 months), all patients were examined for any postoperative complications associated with the recession. Complications were defined as the presence of postoperative infection, wound dehiscence, nerve problems, decreased muscle strength, scar problems, or calcaneus gait (overlengthening). Uncomplicated outcome was defined as absence of all these complications and return to regular activity, both occurring during a follow-up of at least 6 months. Postsurgical complications developed in 9 (6%) of the 126 patients: 6 (4%) had scar problems, 2 (1.33%) had wound dehiscence, 2 (1.33%) had infection, 3 (2%) had nerve problems, and 1 (0.67%) developed complex regional pain syndrome. No patient complained of either a limp or gait disturbance. Neither persistent decrease in muscle strength nor calcaneus gait was seen. These data suggest that the open gastrocnemius recession procedure has low associated morbidity.

  17. Recessive congenital myotonia resulting from maternal isodisomy of chromosome 7: a case report

    PubMed Central

    2009-01-01

    Autosomal dominant (Thomsen) and recessive (Becker) congenital myotonia are two different non dystrophic disorders, due to allelic mutations of the muscle chloride channel gene, located on chromosome 7q35. More than two thirds of the muscle chloride channel gene mutations occur independently in unique families and cause the recessive form of the disease. Becker disease is more common and severe than Thomsen disease. Here, we report on the clinical and molecular data of the first patient with maternal uniparental disomy for chromosome 7 and recessive congenital myotonia. The proband is a 15-year-old male, homozygous for a missense mutation within muscle chloride channel gene, showing few characteristic signs of the Silver Russell Syndrome. PMID:20181190

  18. Combined Regenerative and Mucogingival Treatment of Deep Intrabony Defects Associated with Buccal Gingival Recession: Two Case Reports.

    PubMed

    Santoro, Giacomo; Zucchelli, Giovanni; Gherlone, Enrico

    The case reports presented in this article describe a surgical approach for improving root coverage and regenerative parameters in deep intrabony defects associated with buccal gingival recession. A mandibular canine and a maxillary premolar were treated. The surgical technique consisted of a connective tissue graft (CTG) that was placed and sutured at the inner surface of a coronally advanced envelope flap (CAF), thickening the buccal soft tissue wall of the most coronal extension of the intrabony defect and treated with biomaterials as scaffold. No palatal/lingual flap was elevated. Two years after the surgery, clinically significant root coverage, increased buccal keratinized tissue height and thickness, some minor improvement in the position of the interdental papilla, and clinical attachment level gain were achieved. The radiographs showed bone fill of the intrabony components of the defects. This report encourages a novel application of CAF + CTG + biomaterials to improve both esthetic and regenerative parameters in deep intrabony defects associated with gingival recessions.

  19. Inheritance of idiopathic torsion dystonia among Jews.

    PubMed Central

    Zilber, N; Korczyn, A D; Kahana, E; Fried, K; Alter, M

    1984-01-01

    Idiopathic torsion dystonia (ITD) has long been considered to be genetically determined, but the pattern of inheritance has been unclear. It has been suggested that inheritance may differ in Jews and non-Jews. In the present study, data gathered in a nationwide survey of ITD in Israel were analysed. Between 1969 and 1980, 47 patients were collected, of whom 40 were of European origin. In these European Jews, the ITD frequency was about 1:23 000 live births, which was five-fold greater than in Jews of Afro-Asian origin. Assuming that all cases fit the same genetic model, an X linked or a simple autosomal recessive model of inheritance did not agree well with our data. An autosomal dominant model with low penetrance could have accounted for our observations and would yield an ITD gene frequency in European Jews of 3 to 4:100 000. In view of the increased ages of their fathers, the isolated cases may have included some new mutations. Multifactorial inheritance was also possible. However, it may be inappropriate to assume that all cases have the same genetic basis, or even that all are inherited. PMID:6694180

  20. Primer in Genetics and Genomics, Article 4-Inheritance Patterns.

    PubMed

    Aiello, Lisa B; Chiatti, Beth Desaretz

    2017-07-01

    Since the completion of the Human Genome Project, much has been uncovered about inheritance of various illnesses and disorders. There are two main types of inheritance: Mendelian and non-Mendelian. Mendelian inheritance includes autosomal dominant, autosomal recessive, X-linked, and Y-linked inheritance. Non-Mendelian inheritance includes mitochondrial and multifactorial inheritance. Nurses must understand the types of inheritance in order to identify red flags that may indicate the possibility of a hereditary disorder in a patient or family.

  1. A case report of novel mutation in PRF1 gene, which causes familial autosomal recessive hemophagocytic lymphohistiocytosis.

    PubMed

    Bordbar, Mohammad Reza; Modarresi, Farzaneh; Farazi Fard, Mohammad Ali; Dastsooz, Hassan; Shakib Azad, Nader; Faghihi, Mohammad Ali

    2017-05-03

    Hemophagocytic Lymphohistiocytosis (HLH) is a life-threatening immunodeficiency and multi-organ disease that affects people of all ages and ethnic groups. Common symptoms and signs of this disease are high fever, hepatosplenomegaly, and cytopenias. Familial form of HLH disease, which is an autosomal recessive hematological disorder is due to disease-causing mutations in several genes essential for NK and T-cell granule-mediated cytotoxic function. For an effective cytotoxic response from cytotoxic T lymphocyte or NK cell encountering an infected cell or tumor cell, different processes are required, including trafficking, docking, priming, membrane fusion, and entry of cytotoxic granules into the target cell leading to apoptosis. Therefore, genes involved in these steps play important roles in the pathogenesis of HLH disease which include PRF1, UNC13D (MUNC13-4), STX11, and STXBP2 (MUNC18-2). Here, we report a novel missense mutation in an 8-year-old boy suffered from hepatosplenomegaly, hepatitis, epilepsy and pancytopenia. The patient was born to a first-cousin parents with no previous documented disease in his parents. To identify mutated gene in the proband, Whole Exome Sequencing (WES) utilizing next generation sequencing was used on an Illumina HiSeq 2000 platform on DNA sample from the patient. Results showed a novel deleterious homozygous missense mutation in PRF1 gene (NM_001083116: exon3: c. 1120 T > G, p.W374G) in the patient and then using Sanger sequencing it was confirmed in the proband and his parents. Since his parents were heterozygous for the identified mutation, autosomal recessive pattern of inheritance was confirmed in the family. Our study identified a rare new pathogenic missense mutation in PRF1 gene in patient with HLH disease and it is the first report of mutation in PRF1 in Iranian patients with this disease.

  2. Ten-year evaluation of conservative and surgical treatment of gingival recession. A case series study.

    PubMed

    Jorgić-Srdjak, K; Bosnjak, A; Plancak, D; Maricević, T

    2000-12-01

    In the last years the treatment of non-inflammatory periodontal diseases has greatly changed. Apico-coronal dimension of gingival tissue is not considered to be of utmost importance, but significance of tissue thickness over each tooth is stressed. Purpose of this study was to show results of conservative and surgical treatment of gingival recession. Sample consisted of two groups of subjects, which have been treated in one of stated ways during ten years. The data was obtained on the beginning and after ten years of recall. Both groups showed increased dimension of keratinized gingiva during observed time with decrease of gingival recession, plaque- and gingival index. It is considered that treatment should start with conservative measures with necessary motivation of the patients. If it does not show improvement, one should consider best surgical method available for each patient. Clinical results show success in both groups, meaning that treatment was properly decided on.

  3. [Autosomal-recessive renal cystic disease and congenital hepatic fibrosis: clinico-anatomic case].

    PubMed

    Rostol'tsev, K V; Burenkov, R A; Kuz'micheva, I A

    2012-01-01

    Clinico-anatomic observation of autosomal-recessive renal cystic disease and congenital hepatic fibrosis at two fetuses from the same family was done. Mutation of His3124Tyr in 58 exon of PKHD1 gene in heterozygous state was found out. The same pathomorphological changes in the epithelium of cystic renal tubules and bile ducts of the liver were noted. We suggest that the autopsy research of fetuses with congenital abnormalities, detected after prenatal ultrasonic screening, has high diagnostic importance.

  4. Complications associated with uni-portal endoscopic gastrocnemius recession in a diabetic patient population: an observational case series.

    PubMed

    Roukis, Thomas S; Schweinberger, Monica H

    2010-01-01

    The purpose of this article was to report the complications associated with uni-portal endoscopic gastrocnemius recession for surgical treatment of pathologic soft tissue ankle equinus contracture in diabetic patients. This is an observational case series involving a retrospective review of prospectively collected data of 23 uni-portal endoscopic gastrocnemius recessions used to treat pathologic soft tissue ankle equinus contracture in 18 consecutive diabetic patients between November 2006 and January 2009. Each patient underwent uni-portal endoscopic gastrocnemius recession under general or spinal anesthesia with thigh tourniquet control in combination with soft tissue and/or osseous reconstructive foot and/or ankle surgery. Patients were kept non-weight bearing based on the index procedure and followed until clinical healing occurred or failure was declared. There were 9 male and 9 female patients with a mean age +/- SD of 69.0 +/- 7.4-years (range: 47.0 to 71.0 years). There were 11 right and 12 left lower limbs involved, with 5 procedures performed bilateral. Complications included 3 conversions to an open incision secondary to difficulty dissecting through excessive adipose tissue, delayed healing of 3 incision sites in patients with uncontrolled diabetes mellitus at the time of surgery, and 3 undercorrections in patients with spastic contractures. The remainder of the procedures were deemed successful with no saphenous nerve, sural nerve, or lesser saphenous vein related injuries occurring. When properly performed, uni-portal endoscopic gastrocnemius recession represents a safe, reliable, and minimally invasive technique useful for correcting pathologic soft tissue ankle equinus contracture in patients with diabetes. A percutaneous tendo-Achilles lengthening should be performed in patients who have marginal arterial inflow that precludes tourniquet use or have a spastic contracture. An open rather than endoscopic gastrocnemius recession should be performed in

  5. Unusual inheritance of primary ciliary dyskinesia (Kartagener's syndrome).

    PubMed Central

    Narayan, D; Krishnan, S N; Upender, M; Ravikumar, T S; Mahoney, M J; Dolan, T F; Teebi, A S; Haddad, G G

    1994-01-01

    Primary ciliary dyskinesia syndrome is characterised by chronic sinusitis, bronchiectasis, and, in 50% of cases, dextrocardia. It is generally believed to be inherited as an autosomal recessive disorder. In this report, we describe a family consisting of a mother and her five male children, the offspring of three different fathers, all of whom have this syndrome. This argues for either an X linked or autosomal dominant pattern of inheritance. Cytogenetic and FISH (fluorescent in situ hybridisation) analyses were done on the mother and one son and were found to be normal. Images PMID:8071978

  6. Evidence for digenic inheritance in some cases of Antley-Bixler syndrome?

    PubMed Central

    Reardon, W.; Smith, A.; Honour, J.; Hindmarsh, P.; Das, D.; Rumsby, G.; Nelson, I.; Malcolm, S.; Ades, L.; Sillence, D.; Kumar, D.; DeLozier-Blanchet, C.; McKee, S.; Kelly, T.; McKeehan, W.; Baraitser, M.; Winter, R.

    2000-01-01

    The Antley-Bixler syndrome has been thought to be caused by an autosomal recessive gene. However, patients with this phenotype have been reported with a new dominant mutation at the FGFR2 locus as well as in the offspring of mothers taking the antifungal agent fluconazole during early pregnancy. In addition to the craniosynostosis and joint ankylosis which are the clinical hallmarks of the condition, many patients, especially females, have genital abnormalities. We now report abnormalities of steroid biogenesis in seven of 16 patients with an Antley-Bixler phenotype. Additionally, we identify FGFR2 mutations in seven of these 16 patients, including one patient with abnormal steroidogenesis. These findings, suggesting that some cases of Antley-Bixler syndrome are the outcome of two distinct genetic events, allow a hypothesis to be formulated under which we may explain all the differing and seemingly contradictory circumstances in which the Antley-Bixler phenotype has been recognised.


Keywords: Antley-Bixler syndrome; FGFR; congenital adrenal hyperplasia; CYP21 deficiency PMID:10633130

  7. Recession Rebound

    ERIC Educational Resources Information Center

    Weinstein, Margery

    2011-01-01

    A return to normal after a crisis is a good thing. Who doesn't want back what once seemed lost? The problem is it usually isn't a simple task figuring out how to patch together a scaled-back training program. When the recession hit in fall 2008, trainers were asked to scale down programming and make do with fewer resources. With a recovery in full…

  8. Recession Rebound

    ERIC Educational Resources Information Center

    Weinstein, Margery

    2011-01-01

    A return to normal after a crisis is a good thing. Who doesn't want back what once seemed lost? The problem is it usually isn't a simple task figuring out how to patch together a scaled-back training program. When the recession hit in fall 2008, trainers were asked to scale down programming and make do with fewer resources. With a recovery in full…

  9. A case report: Autosomal recessive microcephaly caused by a novel mutation in MCPH1 gene.

    PubMed

    Ghafouri-Fard, Soudeh; Fardaei, Majid; Gholami, Milad; Miryounesi, Mohammad

    2015-10-15

    Autosomal Recessive Primary Microcephaly (MCPH-MIM 251200) is distinguished by congenital decrease in occipito-frontal head circumference (OFC) of at least 2 standard deviations (SD) below population average in addition to non-progressive mental retardation, without any prominent neurological disorder. Mutations in MCPH1, which encodes the protein microcephalin have been detected in this disorder. Here we report a consanguineous Iranian family with 2 children affected with microcephaly. Despite the severe mental retardation observed in the male patient, the female patient had normal intelligent with no delay in motor milestones or speech. A novel splice-acceptor site homozygous mutation has been detected in intron 4 of MCPH1 gene (c.322-2A>T) which results in an RNA processing defect with a 15-nucleotide deletion in exon 5 of the mRNA transcript (r.322_336del15, p.R108_Q112del5). This novel mutation has resulted in different phenotypes in affected male and female patients of this family. The sex-specific variations in gene regulation during brain development may partially explain such difference in phenotypes probably in addition to other mechanisms such as modifier genes.

  10. Gastrocnemius recession.

    PubMed

    Anderson, John G; Bohay, Donald R; Eller, Erik B; Witt, Bryan L

    2014-12-01

    The Grand Rapids Arch Collapse classifications create a novel system for categorizing and correlating numerous common foot and ankle conditions related to a falling arch. The algorithm for treating these conditions is exceptionally replicable and has excellent outcomes. Gastrocnemius equinus diagnosis plays a crucial role in the pathology of arch collapse. A contracture of the gastrocnemius muscle is increasingly recognized as the cause of several foot and ankle conditions. The authors have expanded their indications for gastrocnemius recession to include arch pain without radiographic abnormality, calcaneus apophysitis, plantar fasciitis/fibromas, Achilles tendonosis, early-onset diabetic Charcot arthropathy, and neuropathic forefoot ulcers.

  11. Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) - A Polish family with novel SACS mutations.

    PubMed

    Krygier, Magdalena; Konkel, Agnieszka; Schinwelski, Michał; Rydzanicz, Małgorzata; Walczak, Anna; Sildatke-Bauer, Magdalena; Płoski, Rafał; Sławek, Jarosław

    2017-08-17

    Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare hereditary ataxia, characterized by the triad of early-onset cerebellar ataxia, peripheral sensorimotor neuropathy and lower limb spasticity. Although ARSACS is increasingly reported worldwide, we present the first Polish family with a comprehensive clinical and neuropsychological assessment, harboring two novel mutations in the SACS gene. Our results demonstrate the variability in cognitive and behavioral profiles in ARSACS, which is in line with other heredodegenerative ataxias. One should be aware of ARSACS in cases of autosomally recessive inherited ataxias without common mutations. Copyright © 2017 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  12. A case of autosomal recessive woolly hair/hypotrichosis with alternation in severity: deterioration and improvement with age.

    PubMed

    Matsuno, Naoko; Kunisada, Makoto; Kanki, Haruhisa; Simomura, Yutaka; Nishigori, Chikako

    2013-09-01

    Autosomal recessive woolly hair/hypotrichosis (ARWH/H) is a nonsyndromic hair abnormality characterized by sparse, short and curly hair (WH/H). We report the case of a 3-year-old female, with no consanguineous ancestry, who exhibited WH/H. Normal hair was observed at birth, but severe hair loss had developed within the first 6 months; however, her hair density had improved somewhat by age 3. Light microscopy showed hair shaft invaginations, and polarized light microscopy suggested complete medullary disruption of the hair. Direct sequence analysis of peripheral blood showed a homozygous missense mutation in exon 6 of the lipase H gene (LIPH: c.736T>A, p.Cys246Ser), and the exact same mutation was found in the heterozygous state in both parents. The initial deterioration followed by improvement with age observed in this case suggests that the clinical course of ARWH/H may vary among patients with the same mutation in LIPH detected in this case, indicating that additional factors may influence the effect of LIPH on hair development.

  13. Mendelian inheritance in Germany between 1900 and 1910. The case of Carl Correns (1864-1933).

    PubMed

    Rheinberger, H J

    2000-12-01

    Carl Correns (1864-1933) came to recognize Mendel's rules between 1894 and 1900 while trying to find out the mechanism of xenia, that is, the direct influence of the fertilizing pollen on the mother plant in maize and peas among other species. In this paper, I am concerned with the ten years of Correns' work after the annus mirabilis of 1900 until 1910, when the main outlines of the new science of genetics had been established. It is generally assumed that after 1900 Correns quickly began probing the limits of Mendelian inheritance, both as far as the explanatory force of formal transmission genetics and the generality of Mendel's laws are concerned. A careful examination of his papers however shows that he was much more interested in the scope of Mendelian inheritance than in its limits. Even his work with variegated Mirabilis plants, which historiographical folklore still presents as a result of Correns' growing interest in cytoplasmic inheritance, can be shown to have been conducted to corroborate just the opposite, namely, the validity of the nuclear paradigm. The paper will show that Correns' research results in those years (among them the Mendelian inheritance of sex in higher plants) were the outcome of a complex experimental program which involved breeding experiments with dozens of different species.

  14. Arrhythmogenic inherited heart muscle diseases in children.

    PubMed

    Towbin, J A; Bowles, N E

    2001-01-01

    The left ventricle (LV) plays a central role in the maintenance of health of children and adults due to its role as the major pump of the heart. In cases of LV dysfunction, a significant percentage of affected individuals develop signs and symptoms of congestive heart failure, leading to the need for therapeutic intervention. Therapy for these patients include anticongestive medications and, in some, placement of devices such as aortic balloon pump or left ventricular assist device, or cardiac transplantation. In the majority of patients the origin is unknown, leading to the term idiopathic dilated cardiomyopathy. During the past decade, the basis of LV dysfunction has begun to unravel. In approximately 30% to 40% of cases, the disorder is inherited; autosomal dominant inheritance is most common (although X-linked, autosomal recessive and mitochondrial inheritance occurs). In the remaining patients, the disorder is presumed to be acquired, with inflammatory heart disease playing an important role. In the case of familial dilated cardiomyopathy, the genetic basis is beginning to unfold. To date, 2 genes for X-linked familial dilated cardiomyopathy (dystrophin, G4.5) have been identified and 4 genes for the autosomal dominant form (actin, desmin, lamin A/C, delta-sarcoglycan) have been described. In 1 form of inflammatory heart disease, coxsackievirus myocarditis, inflammatory mediators, and dystrophin cleavage play a role in the development of LV dysfunction. This review describes the molecular genetics of LV dysfunction and provide evidence for a "final common pathway" responsible for the phenotype.

  15. Klinefelter syndrome with fabry disease--a case of nondisjunction of the X-chromosome with sex-linked recessive mutation.

    PubMed

    Sadick, Victoria J; Fietz, Michael J; Tchan, Michel C; Kovoor, Pramesh; Thomas, Liza; Sadick, Norman

    2014-12-01

    A 52 year-old male with Klinefelter syndrome presented with chest tightness and rapid atrial fibrillation with hypotension. His echocardiogram demonstrated symmetrical left ventricular hypertrophy with minimal diastolic dysfunction. Subsequent investigations confirmed the diagnosis of Fabry cardiomyopathy. This is the first reported case of Klinefelter syndrome with homozygous sex-linked recessive mutation presenting primarily with cardiac manifestation.

  16. [A case of mannosidosis type II].

    PubMed

    Szleper, M; Zaremba, J; Czartoryska, B

    1991-01-01

    A case of L-mannosidosis, a recessively inherited thesaurosis, is reported. Since birth the patient had evidence of immunodeficiency. The neurological manifestations developed during adolescence with slurred and slow speech with scanning, muscle flaccidity, sings of Trömner and Jacobson, intentional tremor, equilibrium disturbances. After many laboratory investigations the tests for inherited metabolic disorders made the correct diagnosis possible.

  17. A Rare Case of Multiple Rice Bodies in Glenohumeral Joint, Subscapular Recess and Along Long Head of Biceps

    PubMed Central

    Chalasani, Prashanth; Koduru, Satyakumar; Mikkineni, Kavya

    2016-01-01

    Introduction: Synovial chondromatosis is a rare, generally benign condition which affects the synovial membranes and commonly involves the large joints such as the knee, and hip. It is usually mono-articular and more common in males. Synovial chondromatosis is characterized by the presence of multiple cartilaginous nodules in the joint synovium. The definitive diagnosis is achieved after the pathological examination of the synovial tissue. It can be very destructive and can cause severe osteoarthritis, pain and malignant transformation. We present a rare case of primary synovial chondromatosis of the shoulder joint in a 31-year-old male patient Case presentation: A 31-year-old man presented with pain and restricted movements of left shoulder for past 6 months, which was insidious in onset and gradually progressive. He had no history of trauma, fever, loss of appetite or weight loss. No tenderness or warmth over shoulder joint was observed. Restriction of movements was observed in all directions. No abnormality was detected in central nervous, cardiovascular, respiratory, genitourinary, or gastrointestinal systems. Routine pre-operative investigations (including liver function and renal function tests) were within the normal limit, serological investigation for rheumatoid arthritis was negative. Excision biopsy of loose bodies was performed. Biopsy reported histological features ofsynovial chondromatosis. Conclusion: Synovial osteochondromatosis of shoulder joint, subscapular recess and along the long head of biceps is a rare case (less than 5% cases reported till date). Understanding the pathology, recognizing the radiographic and MRI appearance of primary synovial chondromatosis and differentiating it from secondary form, malignancy and other synovial pathologies are important in the diagnosis and clinical management of these patients. PMID:28116270

  18. [Inherited aplastic anemias].

    PubMed

    Esteves, A C; Freitas, O; Almeida, T; Rosado, L

    2010-08-01

    The inherited aplastic anaemias are a heterogeneous group of disorders characterized by bone marrow failure, frequent association with one or more somatic anomalies and increased risk of cancer. They are rare disorders, usually diagnosed at paediatric age, and have significant premature mortality. The authors report 11 cases of inherited aplastic anaemias, 8 of Fanconi's anaemia and 3 of Dyskeratosis congenita. These cases were diagnosed in the last 14 years in the Dona Estefânia Hospital.

  19. Mardini-Nyhan association (lung agenesis, congenital heart, and thumb anomalies): three new cases and possible recurrence in a sib-is there a distinct recessive syndrome?

    PubMed

    Hastings, Rob; Harding, David; Donaldson, Alan; Liebling, Rachel; Hayes, Alison; Kraus, Alison; Joss, Shelagh; Narayanaswamy, Shuba; Turnpenny, Peter; Smithson, Sarah

    2009-12-01

    In 1985, Mardini and Nyhan described three patients from consanguineous families with unilateral complete/partial lung agenesis, congenital cardiac defects, and ipsilateral thumb anomalies. Although there have been many reports of lung agenesis with other malformations, especially hemifacial microsomia and radial ray anomalies, very few demonstrate this triad of defects. We describe three patients with the Mardini-Nyhan association which may represent a distinct entity, although this remains uncertain at present. A fourth patient is also described, the sister of one of the other patients, with complex congenital cardiac disease and bilateral lung lobation abnormalities. This is the first reported incidence of a possible recurrence within a family and suggests, together with the consanguinity observed by Mardini and Nyhan, that recessive inheritance should be considered in genetic counseling for this disorder.

  20. Gingival Recession: Review and Strategies in Treatment of Recession

    PubMed Central

    Pradeep, Koppolu; Rajababu, Palaparthy; Satyanarayana, Durvasula; Sagar, Vidya

    2012-01-01

    One of the most common esthetic concerns associated with the periodontal tissues is gingival recession. Gingival recession is the exposure of root surfaces due to apical migration of the gingival tissue margins; gingival margin migrates apical to the cementoenamel junction. Although it rarely results in tooth loss, marginal tissue recession is associated with thermal and tactile sensitivity, esthetic complaints, and a tendency toward root caries. This paper reviews etiology, consequences, and the available surgical procedures for the coverage of exposed root surfaces, including three case reports. PMID:23082256

  1. Subepithelial connective tissue graft associated with apicoectomy and root-end fillings in the treatment of deep localized gingival recession with apex root exposure: case report.

    PubMed

    Kahn, Sergio; Egreja, Andre Medina Coeli; Barceleiro, Marcos de Oliveira

    2009-08-01

    Periodontal reconstructive surgery procedures seek to correct mucogingival defects, including gingival recession. This case report describes the use of a subepithelial connective tissue graft (SCTG) associated with root-end fillings using mineral trioxide aggregate (MTA) for the treatment of Miller Class II recession with root apex exposure. A partial-thickness double pedicle flap was made, followed by root preparation with curette and bur finishing. The exposed root apex was removed and the canal was filled with MTA. An SCTG taken from the palate was placed over the root surface and covered with the double pedicle flap. Twelve months after treatment, a reduction from 11 mm to 1 mm in gingival recession was achieved, covering 91% of the root. Repair in the periapical region was determined with radiographs. A 1.0-mm probing depth was measured, and no bleeding was observed on probing. There was an adequate keratinized tissue band, along with esthetic tissue contour and coloration. This case report serves as an example of how the grafting of subepithelial connective tissue can be successfully accomplished in tandem with MTA for the treatment of isolated Miller Class II gingival recession with root apex exposure. (Int J Periodontics Restorative Dent 2009;29:445-449.).

  2. Glacial recession in the Tropical Andes from the Little Ice Age: the case of Ampato Volcanic Complex (Southern Peru

    NASA Astrophysics Data System (ADS)

    Alcalá, J.; Palacios, D.; Zamorano, J. J.

    2010-03-01

    Data published over the last decade reveal substantial glacial recession in the tropical Andes since the Little Ice Age (LIA), (Ramirez, et al., 2001; Rabatel, et al., 2005; Rabatel, et al., 2008; Vuille, et al., 2008; Hastenrath, 2009; Jomelli, et al., 2009), and a growing rate of recession since the 1980’s caused by global warming (Ramirez, et al., 2001; Vuille, et al., 2008). Today there is great interest in the evolution of these ice masses due to heightened awareness of climate change and of the strategic importance that glaciers have as a hydrologic resource for communities in arid climate zones in the tropical Andes (Mark, 2008; Vuille et al., 2008). Cordillera Blanca forms part of the Andes Mountains of northern Peru, and is a chosen site for many studies on glacier evolution. Vuille et al. 2008 determined that a considerable area of ice mass was lost at Huascarán-Chopicalqui glacier (18% from 1920-1970) and Astesonraju glacier (20% from 1962-2003). Studies at Coropuna volcano, which has the most extensive glacier field in the western range of southern Peru, also report a strong melting trend that began with only minimal recession from 1955-1986 (4%), but increased to 14% from 1986-2007 (Úbeda et al., 2009). Only a few of the Andes glaciers are consistently monitored, and the most comprehensive data are for Chacaltaya and Zongo glaciers (16º S) in Bolivia. Since the maximum LIA, Chacaltaya has lost 89% of its surface area, particularly in recent years. By 1983, the totaled loss was five times the shrinkage for the period 1940-1963 (Ramirez, et al., 2001). Zongo glacier maintained equilibrium from 1956-1975, but later experienced a period dominated by continuous recession (Soruco, et al., 2009). This study expands current knowledge of glacier evolution since the LIA in the Central Volcanic Zone (CVZ; 14º - 27º S) (Stern, 2004) of the Andes. The study site was chosen in an area that had never been used for preliminary research of this type, concretely

  3. Coronally advanced flap with two different techniques for the treatment of multiple gingival recessions: A pilot prospective comparative case series.

    PubMed

    Barrella, Guilherme Emerson; Kolbe, Maria Fernanda; Ribeiro, Fernanda Vieira; Casati, Marcio Zaffalon; Casarin, Renato Correa; Cirano, Fabiano Ribeiro; Pimentel, Suzana Peres

    2016-01-01

    The objective of this prospective study was to compare the clinical outcomes of coronally advanced flap (CAF) using two different surgical strategies in the treatment of multiple gingival recessions. Ten patients presenting with a total of 81 Miller class I gingival recessions were included. Recessions were randomly treated according to a split-mouth design by means of CAF with oblique interdental incisions (OBL technique), or CAF with horizontal interdental incisions (HOR technique). Marginal gingival recession (REC), clinical attachment level (CAL), pocket probing depth (PPD), height of keratinized tissue (HKT), and thickness of keratinized tissue (TKT) were measured at baseline, and 3 and 6 months after treatment. Patient-centered outcomes concerning morbidity and improvement in the esthetic appearance were recorded using a visual analog scale (VAS). Both groups showed significant reductions in REC and gains in CAL throughout the study (P < .05). At 3 months, OBL-treated sites showed greater root coverage than HOR-treated sites (P < .05), although no intergroup differences were observed at 6 months (P > .05). There was an increase in HKT only in the OBL group at 6 months from baseline (P < .05). No differences between therapies were revealed concerning morbidity (P > .05), whereas a higher satisfaction with the esthetic appearance was reported for the OBL technique 6 months postsurgery (P < .05). Although both surgical approaches may provide satisfactory root coverage, use of the OBL technique promoted additional benefits in terms of esthetic perception after the management of multiple gingival recessions.

  4. Neonatal Marfan Syndrome: Report of a Case with an Inherited Splicing Mutation outside the Neonatal Domain.

    PubMed

    Le Gloan, Laurianne; Hauet, Quentin; David, Albert; Hanna, Nadine; Arfeuille, Chloé; Arnaud, Pauline; Boileau, Catherine; Romefort, Bénédicte; Benbrik, Nadir; Gournay, Véronique; Joram, Nicolas; Baron, Olivier; Isidor, Bertrand

    2016-02-01

    We report a child and her mother affected by Marfan syndrome. The child presented with a phenotype of neonatal Marfan syndrome, revealed by acute and refractory heart failure, finally leading to death within the first 4 months of life. Her mother had a common clinical presentation. Genetic analysis revealed an inherited FBN1 mutation. This intronic mutation (c.6163+3_6163+6del), undescribed to date, leads to exon 49 skipping, corresponding to in-frame deletion of 42 amino acids (p.Ile2014_Asp2055del). FBN1 next-generation sequencing did not show any argument for mosaicism. Association in the same family of severe neonatal and classical Marfan syndrome illustrates the intrafamilial phenotype variability.

  5. Neonatal Marfan Syndrome: Report of a Case with an Inherited Splicing Mutation outside the Neonatal Domain

    PubMed Central

    Le Gloan, Laurianne; Hauet, Quentin; David, Albert; Hanna, Nadine; Arfeuille, Chloé; Arnaud, Pauline; Boileau, Catherine; Romefort, Bénédicte; Benbrik, Nadir; Gournay, Véronique; Joram, Nicolas; Baron, Olivier; Isidor, Bertrand

    2016-01-01

    We report a child and her mother affected by Marfan syndrome. The child presented with a phenotype of neonatal Marfan syndrome, revealed by acute and refractory heart failure, finally leading to death within the first 4 months of life. Her mother had a common clinical presentation. Genetic analysis revealed an inherited FBN1 mutation. This intronic mutation (c.6163+3_6163+6del), undescribed to date, leads to exon 49 skipping, corresponding to in-frame deletion of 42 amino acids (p.Ile2014_Asp2055del). FBN1 next-generation sequencing did not show any argument for mosaicism. Association in the same family of severe neonatal and classical Marfan syndrome illustrates the intrafamilial phenotype variability. PMID:27022329

  6. Autosomal recessive pericentral pigmentary retinopathy.

    PubMed

    Traboulsi, E I; O'Neill, J F; Maumenee, I H

    1988-11-15

    A brother and sister, born to consanguineous parents, had pigmentary retinopathy in a pericentral distribution. The retinopathy was noted in infancy when the siblings were examined for strabismus. The optic disks, maculae, and retinal vessels were normal. There was mild reduction in amplitude of both scotopic and photopic electroretinographic responses. Both patients had moderate hyperopic astigmatism and esotropia. The fundus and visual acuity remained unchanged over periods of nine and 13 years in the brother and sister, respectively. Results of ocular examinations on the father, mother, and an older sister were normal. These findings support an autosomal recessive mode of inheritance in this family with pericentral pigmentary retinopathy.

  7. Impacts of Scheduling Recess before Lunch in Elementary Schools: A Case Study Approach of Plate Waste and Perceived Behaviors

    ERIC Educational Resources Information Center

    Strohbehn, Catherine H.; Strohbehn, Garth W.; Lanningham-Foster, Lorraine; Litchfield, Ruth A.; Scheidel, Carrie; Delger, Patti

    2016-01-01

    Purpose/Objectives: Recess Before Lunch (RBL) for elementary students is considered a best practice related to increased nutrient intakes at lunch, decreased afternoon behavioral issues, and increased afternoon learning efficiency; however, school characteristics, such as amount of time for lunch, offer vs. serve, and scheduling factors can…

  8. Impacts of Scheduling Recess before Lunch in Elementary Schools: A Case Study Approach of Plate Waste and Perceived Behaviors

    ERIC Educational Resources Information Center

    Strohbehn, Catherine H.; Strohbehn, Garth W.; Lanningham-Foster, Lorraine; Litchfield, Ruth A.; Scheidel, Carrie; Delger, Patti

    2016-01-01

    Purpose/Objectives: Recess Before Lunch (RBL) for elementary students is considered a best practice related to increased nutrient intakes at lunch, decreased afternoon behavioral issues, and increased afternoon learning efficiency; however, school characteristics, such as amount of time for lunch, offer vs. serve, and scheduling factors can…

  9. Maternally inherited architecture in tertiary leaf beetles: paleoichnology of cryptocephaline fecal cases in Dominican and Baltic amber.

    PubMed

    Chaboo, Caroline S; Engel, Michael S; Chamorro-Lacayo, Maria Lourdes

    2009-09-01

    Complex ethological adaptations and intraspecific interactions leave few fossil traces. We document three Dominican (20 million years old [myo]) and Baltic (45 myo) amber fossils that exhibit firm evidence of highly integrated interactions between mothers and offspring in the diverse camptosomate lineage of beetles (Chrysomelidae, leaf beetles). As in contemporary species, these hard cases were initially constructed by mothers, then inherited and retained by offspring, which then elaborate this protective domicile with an unusual but economical building material, their feces. The three fossils are classified in the Subfamily Cryptocephalinae; two are classified in the tribe Chlamisini based on morphological evidence-the flattened head lacking a sharp keel and long legs with simple recurved untoothed claws. These diagnostic features are not clearly visible in the third specimen to permit more refined identification. These fossils provide more precise paleontological dating of tribal nodes within the cryptocephaline radiation of leaf beetles. These fossils are the first and earliest evidence of mother-offspring interaction, building behavior, and fecal recycling in Camptosomata beetles and of inheritance of architectural structures in beetles.

  10. Maternally inherited architecture in tertiary leaf beetles: paleoichnology of cryptocephaline fecal cases in Dominican and Baltic amber

    NASA Astrophysics Data System (ADS)

    Chaboo, Caroline S.; Engel, Michael S.; Chamorro-Lacayo, Maria Lourdes

    2009-09-01

    Complex ethological adaptations and intraspecific interactions leave few fossil traces. We document three Dominican (20 million years old [myo]) and Baltic (45 myo) amber fossils that exhibit firm evidence of highly integrated interactions between mothers and offspring in the diverse camptosomate lineage of beetles (Chrysomelidae, leaf beetles). As in contemporary species, these hard cases were initially constructed by mothers, then inherited and retained by offspring, which then elaborate this protective domicile with an unusual but economical building material, their feces. The three fossils are classified in the Subfamily Cryptocephalinae; two are classified in the tribe Chlamisini based on morphological evidence—the flattened head lacking a sharp keel and long legs with simple recurved untoothed claws. These diagnostic features are not clearly visible in the third specimen to permit more refined identification. These fossils provide more precise paleontological dating of tribal nodes within the cryptocephaline radiation of leaf beetles. These fossils are the first and earliest evidence of mother-offspring interaction, building behavior, and fecal recycling in Camptosomata beetles and of inheritance of architectural structures in beetles.

  11. Autosomal Recessive Hypophosphatasia Manifesting in Utero with Long Bone Deformity but Showing Spontaneous Postnatal Improvement

    PubMed Central

    Stevenson, David A.; Carey, John C.; Coburn, Stephen P.; Ericson, Karen L.; Byrne, Janice L. B.; Mumm, Steven; Whyte, Michael P.

    2008-01-01

    Context: Hypophosphatasia (HPP) is a heritable metabolic disorder of the skeleton that includes variable expressivity conditioned by gene dosage effect and the variety of mutations in the tissue nonspecific alkaline phosphatase (TNSALP) gene. Patient age when skeletal problems first manifest generally predicts the clinical course, with perinatal HPP causing bone disease in utero with postnatal lethality. Objective: Our objective was to identify TNSALP mutations and characterize the inheritance pattern of a family with clinically variable HPP with one child manifesting in utero with long bone deformity but showing spontaneous prenatal and postnatal improvement. Design: TNSALP enzyme and substrate analysis and TNSALP mutation analysis were performed on all family members. Patients: A boy with HPP showing long bone deformity that spontaneously improved in utero and after birth is described. His older brother has the childhood form of HPP without findings until after infancy. His parents and twin sister are clinically unaffected. Results: Both boys are compound heterozygotes for the same missense mutations in TNSALP, documenting autosomal recessive inheritance for their HPP. The parents each carry one defective allele. Conclusions: The patient is an autosomal recessive case of HPP with prenatal long bone deformity but with spontaneous prenatal and postnatal improvement. Thus, prenatal detection by sonography of bowing of long bones from HPP, even with autosomal recessive inheritance, does not necessarily predict lethality but can represent variable expressivity or the effects of modifiers on the TNSALP defect(s). PMID:18559907

  12. Child access to the nutritional safety net during and after the Great Recession: The case of WIC.

    PubMed

    Jackson, Margot I; Mayne, Patrick

    2016-12-01

    Because children disproportionately live in poverty, they are especially vulnerable during economic crises, making the social safety net a key buffer against the effects of economic disadvantage on their development. The Great Recession of 2007-2009 had strong and lasting effects on American children and families, including striking negative effects on their health environments. Understanding access to the health safety net during this time of increased economic need, as well as the extent to which all children-regardless of age, income or race/ethnicity-share in the increased use of transfer programs, is therefore important in identifying the availability and accessibility of government assistance for those in need. Focusing on the Special Supplemental Nutrition Program for Women, Infants and Children (WIC) program because of its strong effects on child development, we use longitudinal data from the Survey of Income and Program Participation (SIPP) to examine change and stability in children's WIC enrollment before, during and after the recession. Specifically, we examine: 1) whether children's WIC enrollment increased alongside changing family income, and 2) the extent to which changes in participation were shared by all subpopulations, regardless of age, income, and race/ethnicity. Analyses reveal that WIC participation among eligible children increased leading up to, during, and after the Great Recession, suggesting that the program was responsive to increasing economic need. Examining the distribution of WIC enrollment across demographic groups largely reveals a pattern of stable inequality in access and "take up." Children born to poorer and less-educated mothers were more likely to be enrolled prior to the recession, and these differences remain mostly constant during and after the recession. Eligible Hispanic children had consistently higher enrollment, particularly among those in families with foreign-born mothers. The findings suggest that not all

  13. Dystrophic epidermolysis bullosa with one dominant and one recessive mutation of the COL7A1 gene in a child with deafness.

    PubMed

    Weinel, Sarah; Lucky, Anne W; Uitto, Jouni; Pfendner, Ellen G; Choo, Daniel

    2008-01-01

    Dystrophic epidermolysis bullosa can be inherited in autosomal dominant and recessive forms, the former usually expressed as a milder phenotype, although mild forms of recessive dystrophic epidermolysis bullosa can occur. We present a patient who was found to be a compound heterozygote, inheriting a dominant mutation from his father and a recessive mutation from his mother, resulting in a clinically severe case of dystrophic epidermolysis bullosa. Mutations in the gene for collagen VII (COL7A1) have been documented in both types of dystrophic epidermolysis bullosa. Our patient has also been diagnosed with bilateral auditory neuropathy, a disorder coincidentally also mapped to a nearby gene on chromosome 3p21 (the transmembrane inner ear expressed gene, TMIE).

  14. Rift inheritance in orogenes: a case study from the Western Pyrenees

    NASA Astrophysics Data System (ADS)

    Masini, E.; Manatschal, G.; Tugend, J.; Kusznir, N. J.; Flament, J.

    2012-12-01

    In plate tectonics, there is a general assumption that rifted margins represent most of the former material accreted into collisional orogenic prisms. In this regard, the former architecture, structures and composition of rifted margins, i.e. the pre-orogenic inheritances, play undoubtedly a major role during tectonic inversion. Studies have shown that rifted margins are more complex than a succession of tilted blocks. Indeed, the discovery of hyper-extended domains, where low-angle detachments replace high-angle normal faults and mantle material is exhumed to the seafloor implies a revision of the margin's template used in orogenic models. Because of overprint, the role of rift inheritance in orogenes remains often underestimated. The Pyrenees, located along the Iberian-European plate boundary, can be considered as one of the best places to study the reactivation of hyper-extended rifts. In this orogen, the Late Cretaceous and Tertiary convergence overprints a Latest Jurassic to Lower Cretaceous intracontinental rift linked with the opening of the North Atlantic. There, Albian hyper-extended rift basins developed where deep crustal and mantle rocks were exhumed along low-angle detachments to the seafloor. In this work we discuss the example of the Mauléon-Arzacq domain, which escaped from the most pervasive deformation because of its specific location between the western termination of the chain and the Bay of Biscay oceanic domain. Combining field study with subsurface geophysical and drillhole data, we show that the overall rift domain is asymmetric. The northern European upper plate is on the hangingwall of low-angle detachment systems affecting the southern Iberian Lower plate. The upper plate records depth-dependent crustal thinning and the development of a syn-rift sag basin. In contrast, the lower plate resulted from the hyper-extension of Iberian continental crust accommodated at the surface by two diachronous top-basement detachment systems. The first

  15. Novel PRRT2 mutations in paroxysmal dyskinesia patients with variant inheritance and phenotypes.

    PubMed

    Liu, X-R; Wu, M; He, N; Meng, H; Wen, L; Wang, J-L; Zhang, M-P; Li, W-B; Mao, X; Qin, J-M; Li, B-M; Tang, B; Deng, Y-H; Shi, Y-W; Su, T; Yi, Y-H; Tang, B-S; Liao, W-P

    2013-03-01

    Paroxysmal dyskinesias (PDs) are a group of episodic movement disorders with marked variability in clinical manifestation and potential association with epilepsy. PRRT2 has been identified as a causative gene for PDs, but the phenotypes and inheritance patterns of PRRT2 mutations need further clarification. In this study, 10 familial and 21 sporadic cases with PDs and PDs-related phenotypes were collected. Genomic DNA was screened for PRRT2 mutations by direct sequencing. Seven PRRT2 mutations were identified in nine (90.0%) familial cases and in six (28.6%) sporadic cases. Five mutations are novel: two missense mutations (c.647C>G/p.Pro216Arg and c.872C>T/p.Ala291Val) and three truncating mutations (c.117delA/p.Val41TyrfsX49, c.510dupT/p.Leu171SerfsX3 and c.579dupA/p.Glu194ArgfsX6). Autosomal dominant inheritance with incomplete penetrance was observed in most of the familial cases. In the sporadic cases, inheritance was heterogeneous including recessive inheritance with compound heterozygous mutations, inherited mutations with incomplete parental penetrance and de novo mutation. Variant phenotypes associated with PRRT2 mutations, found in 36.0% of the affected cases, included febrile convulsions, epilepsy, infantile non-convulsive seizures (INCS) and nocturnal convulsions (NC). All patients with INCS or NC, not reported previously, displayed abnormalities on electroencephalogram (EEG). No EEG abnormalities were recorded in patients with classical infantile convulsions and paroxysmal choreoathetosis (ICCA)/paroxysmal kinesigenic dyskinesia (PKD). Our study further confirms that PRRT2 mutations are the most common cause of familial PDs, displaying both dominant and recessive inheritance. Epilepsy may occasionally occur in ICCA/PKD patients with PRRT2 mutations. Variant phenotypes INCS or NC differ from classical ICCA/PKD clinically and electroencephalographically. They have some similarities with, but not identical to epilepsy, possibly represent an overlap between

  16. [Gingival recessions and orthodontics].

    PubMed

    Renkema, A M; Padmos, J A D; de Quincey, G de

    2015-11-01

    Gingival recessions represent the most visible periodontal disease. The prevalence of gingival recessions is high. The root surface is literally exposed to negative influences such as erosion, abrasion, discoloration and decay. Moreover, gingival recessions can affect the quality of life by increased thermal sensitivity and reduced dento-gingival aesthetics. The aetiology of gingival recessions is complex and considered to be multifactorial. In order to prevent the development of gingival recessions during and after orthodontic treatment, several factors should be taken into account, among which maintenance of optimal oral hygiene and respect for the 'biological envelope' are decisive. Once gingival recessions have developed, orthodontic therapy can play a positive role in their treatment.

  17. Inherited disorders of desmosomes.

    PubMed

    McGrath, John A

    2005-11-01

    Desmosomes are highly organized intercellular junctions that provide mechanical integrity to tissues by anchoring intermediate filaments to sites of strong adhesion. These cell-cell adhesion junctions are found in skin, heart, lymph nodes and meninges. Over the last 8 years, several naturally occurring human gene mutations in structural components of desmosomes have been reported. These comprise autosomal dominant or recessive mutations in plakophilin 1, plakophilin 2, desmoplakin, plakoglobin, desmoglein 1, desmoglein 4 and corneodesmosin. These discoveries have often highlighted novel or unusual phenotypes, including abnormal skin fragility and differentiation, and developmental anomalies of various ectodermal appendages, especially hair. Some desmosomal gene mutations may also result in cardiac disease, notably cardiomyopathy. This article describes the spectrum of clinical features that may be found in the inherited disorders of desmosomes and highlights the key functions of several of the desmosomal proteins in tissue adhesion and cell biology.

  18. Two clinicopathological cases of a dominantly inherited, adult onset orthochromatic leucodystrophy

    PubMed Central

    Letournel, F; Etcharry-Bouyx, F; Verny, C; Barthelaix, A; Dubas, F

    2003-01-01

    The first patient, aged 58 years, had frontal dementia and epilepsy; the second, aged 38 years, had motor signs and dementia, but no epilepsy. The histopathological features of our two cases were leucodystrophy of orthochromatic subtype. However, the radiological features (MRI and mostly FLAIR sequences) of the first case did not suggest leucodystrophy. PMID:12700318

  19. Novel large deletion in the ACTA1 gene in a child with autosomal recessive nemaline myopathy.

    PubMed

    Friedman, Bethany; Simpson, Kara; Tesi-Rocha, Carolina; Zhou, Delu; Palmer, Cheryl A; Suchy, Sharon F

    2014-04-01

    Nemaline myopathy (NM) is a genetically and clinically heterogeneous disorder resulting from a disruption of the thin filament proteins of the striated muscle sarcomere. The disorder is typically characterized by muscle weakness including the face, neck, respiratory, and limb muscles and is clinically classified based on the age of onset and severity. Mutations in the ACTA1 gene contribute to a significant proportion of NM cases. The majority of ACTA1 gene mutations are missense mutations causing autosomal dominant NM by producing an abnormal protein. However, approximately 10% of ACTA1 gene mutations are associated with autosomal recessive NM; these mutations are associated with loss of protein function. We report the first case of a large deletion in the ACTA1 gene contributing to autosomal recessive NM. This case illustrates the importance of understanding disease mechanisms at the molecular level to accurately infer the inheritance pattern and potentially aid with clinical management. Copyright © 2014. Published by Elsevier B.V.

  20. Neonatal diabetes mellitus and cerebellar hypoplasia/agenesis: report of a new recessive syndrome

    PubMed Central

    Hoveyda, N.; Shield, J.; Garrett, C.; Chong, W; Beardsall, K.; Bentsi-Enchill, E.; Mallya, H.; Thompson, M.

    1999-01-01

    Classical neonatal diabetes mellitus is defined as hyperglycaemia occurring within the first six weeks of life in term infants. Cerebellar agenesis is rare. We report three cases of neonatal diabetes mellitus, cerebellar hypoplasia/agenesis, and dysmorphism occurring within a highly consanguineous family. This constellation of abnormalities has not previously been described. Two of these cases are sisters and the third case is a female first cousin. The pattern of inheritance suggests this is a previously undescribed autosomal recessive disorder. Prenatal diagnosis of the condition in this family was possible by demonstration of the absence of the cerebellum and severe IUGR.


Keywords: cerebellar agenesis/hypoplasia; neonatal diabetes mellitus; dysmorphic features; autosomal recessive PMID:10507728

  1. Inherited t(9;22) as the cause of DiGeorge syndrome: a case report.

    PubMed

    Shuib, Salwati; Abdul Latif, Zarina; Abidin, Nor Zarina Zainal; Akmal, Sharifah Noor; Zakaria, Zubaidah

    2009-12-01

    DiGeorge syndrome is associated with microdeletion of chromosome 22q11.2. Most cases occur sporadically although vertical transmission has been documented. We report a rare case of DiGeorge syndrome in an 8-year-old girl. Blood sample of the patient was cultured and harvested following standard procedure. All of the 20 cells analysed showed a karyotype of 45, XX, -22, t (9;22) (p23; q11.2). Cytogenetic investigation done on the patient's mother revealed that she was the carrier for the translocation. Her karyotype was 46, XX, t (9;22) (p23; q11.2). Fluorescence in situ hybridisation (FISH) analysis using TUPLE1 and N25 (Vysis, USA) probes showed deletion of the 22q11.2 region in the patient, confirming the diagnosis of DiGeorge syndrome. FISH analysis showed no deletion of the region in the mother.

  2. Shaped Recess Flow Control

    NASA Technical Reports Server (NTRS)

    Shyam, Vikram (Inventor); Poinsatte, Philip (Inventor); Thurman, Douglas (Inventor)

    2017-01-01

    One or more embodiments of techniques or systems for shaped recess flow control are provided herein. A shaped recess or cavity can be formed on a surface associated with fluid flow. The shaped recess can be configured to create or induce fluid effects, temperature effects, or shedding effects that interact with a free stream or other structures. The shaped recess can be formed at an angle to a free stream flow and may be substantially "V" shaped. The shaped recess can be coupled with a cooling channel, for example. The shaped recess can be upstream or downstream from a cooling channel and aligned in a variety of manners. Due to the fluid effects, shedding effects, and temperature effects created by a shaped recess, lift-off or separation of cooling jets of cooling channels can be mitigated, thereby enhancing film cooling effectiveness.

  3. Inherited peripheral neuropathies.

    PubMed

    Shy, Michael E

    2011-04-01

    Mutations in genes expressed in Schwann cells and the axons they ensheathe cause the hereditary motor and sensory neuropathies, also known as Charcot-Marie-Tooth disease (CMT). More than 40 different genes have been shown to cause inherited neuropathies; chromosomal localizations of many other distinct inherited neuropathies have been mapped, and new genetic causes for inherited neuropathies continue to be discovered. How to keep track of all of these disorders, when to pursue genetic testing, and what tests to order for specific patients are difficult challenges for any neurologist. This review addresses these issues and provides illustrative cases to help in dealing with them. CMT serves as a living system to identify molecules necessary for normal peripheral nervous system (PNS) function. Understanding how these various molecules interact will provide a better understanding of the pathogenesis of peripheral neuropathies in general as well as other neurodegenerative disorders involving the PNS.

  4. Objective hydrograph baseflow recession analysis

    NASA Astrophysics Data System (ADS)

    Thomas, Brian F.; Vogel, Richard M.; Famiglietti, James S.

    2015-06-01

    A streamflow hydrograph recession curve expresses the theoretical relationship between aquifer structure and groundwater outflow to a stream channel. That theoretical relationship is often portrayed empirically using a recession plot defined as a plot of ln(-dQ/dt) versus ln(Q), where Q is streamflow discharge. Such hydrograph recession plots are commonly used to estimate recession parameters, aquifer properties and for evaluating alternative hydrologic hypotheses. We introduce a comprehensive and objective approach to analyze baseflow recessions with innovations including the use of quantile regression, efficient and objective numerical estimation of dQ/dt, inclusion of groundwater withdrawals, and incorporation of seasonal effects. We document that these innovations when all combined, lead to significant improvements, over previous studies, in our ability to discern the theoretical behavior of stream aquifer systems. A case study reveals that our methodology enables us to reject the simple linear reservoir hypothesis of stream aquifer interactions for watersheds in New Jersey and results in improved correlations between low flow statistics and aquifer properties for those same watersheds.

  5. [Considerations concerning medical knowledge inherited in Mexico from 19th century: the diabetes mellitus case].

    PubMed

    García de Alba-García, Javier Eduardo; Salcedo-Rocha, Ana Leticia; Milke-Najar, María Eugenia; Alonso-Reynoso, Carlos; García de Alba-Verduzco, Javier Eugenio

    2017-01-01

    In Mexico, as in the entire Western world, during the 19th century and the beginnings of the 20th century, medical knowledge developed in a remarkable way and the case of diabetes mellitus was not the exception. This situation, which arose on the basis of the antique paradigm, and which in turn was overthrown by the positivism as the emergent paradigm (with its clinical and anatomical, as well as physiopathological and etiopathological viewpoints), was reflected during the 19th the century through its actors and the communications that opened the access of Mexican medicine to the modernity.

  6. Autosomal recessive chronic granulomatous disease caused by deletion at a dinucleotide repeat.

    PubMed Central

    Casimir, C M; Bu-Ghanim, H N; Rodaway, A R; Bentley, D L; Rowe, P; Segal, A W

    1991-01-01

    Chronic granulomatous disease (CGD) is a rare inherited condition rendering neutrophils incapable of killing invading pathogens. This condition is due to the failure of a multicomponent microbicidal oxidase that normally yields a low-midpoint-potential b cytochrome (cytochrome b245). Although defects in the X chromosome-linked cytochrome account for the majority of CGD patients, as many as 30% of CGD cases are due to an autosomal recessive disease. Of these, greater than 90% have been shown to be defective in the synthesis of a 47-kDa cytosolic component of the oxidase. We demonstrate here in three unrelated cases of autosomal recessive CGD that the identical underlying molecular lesion is a dinucleotide deletion at a GTGT tandem repeat, corresponding to the acceptor site of the first intron-exon junction. Slippage of the DNA duplex at this site may contribute to the high frequency of defects in this gene. Images PMID:2011585

  7. Small operator outwits recession

    SciTech Connect

    Jackson, D.

    1982-12-01

    Explains how Rockcastle, Inc., one of the smallest surface coal mine operators in the West, maintains production during the recession by concentrating on short-term contracts and spot sales to industrial and commercial users. The mining company has selected well established coal brokers to market its product to users such as sugar beet and cement plants, a brewery, steel mill, utility, and a molybdenum mill. Rockcastle produces, on a two-shift schedule, about 1,200 tpd of coal with a total workforce of 20, or approximately 30 tons per manshift. A fleet of 4 scrapers, with dozer-assist in most cases, is capable of removing 5,000 to 6,000 cu yd of overburden and interburden per shift.

  8. Autosomal Recessive Multiple Epiphyseal Dysplasia in a Korean Girl Caused by Novel Compound Heterozygous Mutations in the DTDST (SLC26A2) Gene

    PubMed Central

    Kim, Ok-Hwa; Lee, Hye-Ran; Shin, Sung Jin; Yoo, Won Joon; Park, Woong Yang; Park, Sung Sup; Cho, Sung Im; Choi, In Ho

    2010-01-01

    Multiple epiphyseal dysplasia is caused by heterogenous genotypes involving more than six genes. Recessive mutations in the DTDST gene cause a phenotype of recessive multiple epiphyseal dysplasia (rMED). The authors report a 9-yr old Korean girl with the rMED phenotype having novel compound heterozygous mutations in the DTDST gene, which were inherited from both parents. This is the first Korean rMED case attributed to DTDST mutations, and expands the spectrum of diseases caused by DTDST mutations. PMID:20592910

  9. Global Carrier Rates of Rare Inherited Disorders Using Population Exome Sequences

    PubMed Central

    Fujikura, Kohei

    2016-01-01

    Exome sequencing has revealed the causative mutations behind numerous rare, inherited disorders, but it is challenging to find reliable epidemiological values for rare disorders. Here, I provide a genetic epidemiology method to identify the causative mutations behind rare, inherited disorders using two population exome sequences (1000 Genomes and NHLBI). I created global maps of carrier rate distribution for 18 recessive disorders in 16 diverse ethnic populations. Out of a total of 161 mutations associated with 18 recessive disorders, I detected 24 mutations in either or both exome studies. The genetic mapping revealed strong international spatial heterogeneities in the carrier patterns of the inherited disorders. I next validated this methodology by statistically evaluating the carrier rate of one well-understood disorder, sickle cell anemia (SCA). The population exome-based epidemiology of SCA [African (allele frequency (AF) = 0.0454, N = 2447), Asian (AF = 0, N = 286), European (AF = 0.000214, N = 4677), and Hispanic (AF = 0.0111, N = 362)] was not significantly different from that obtained from a clinical prevalence survey. A pair-wise proportion test revealed no significant differences between the two exome projects in terms of AF (46/48 cases; P > 0.05). I conclude that population exome-based carrier rates can form the foundation for a prospectively maintained database of use to clinical geneticists. Similar modeling methods can be applied to many inherited disorders. PMID:27219052

  10. Inheritance and world variation in thermal requirements for egg hatch in Lymantria dispar (Lepidoptera: Erebidae)

    Treesearch

    M.A. Keena

    2016-01-01

    Mode of inheritance of hatch traits in Lymantria dispar L. was determined by crossing populations nearly fixed for the phenotypic extremes. The nondiapausing phenotype was inherited via a single recessive gene and the phenotype with reduced low temperature exposure requirements before hatch was inherited via a single dominant gene. There was no...

  11. Limb reduction defects and renal dysplasia: confirmation of a new, apparently lethal, autosomal recessive MCA syndrome.

    PubMed

    Schrander-Stumpel, C; de Die-Smulders, C; Fryns, J P; da Costa, J; Bouckaert, P

    1990-09-01

    We report on 2 sibs, a male and a female, who died shortly after birth from respiratory failure. They combined growth retardation with a Potter-like face, complete phocomelia of the upper limbs, rib anomalies (mainly severe hypoplasia of the 6 upper ribs), renal dysplasia, and external genital abnormalities. We hypothesize that these cases represent evidence for the existence of the "new syndrome" described by Ulbright et al. (Am J Med Genet 17:667-668, 1984). This syndrome appears lethal because of the severe renal dysplasia that causes oligohydramnios and pulmonary hypoplasia. Its mode of inheritance seems to be autosomal recessive.

  12. Autosomal recessive bilateral frontal polymicrogyria with ectopia lentis and chorioretinal dystrophy.

    PubMed

    Nooraine, Javeria; Vasudha, Kemmanu; Natesh, Sribhargava; Iyer, Rajesh B; Raghavendra, Seetharam

    2013-10-01

    Polymicrogyria is a type of cortical dysplasia with cortical organizational defect. Bilateral polymicrogyria are distinct with genetic basis in a subset. We hereby report a case of bilateral frontal polymicrogyria (BFP) in association with chorioretinal dystrophy and ectopia lentis (EL) in a 26-year-old lady born of a consanguineous parentage. Her male sibling also had chorioretinal dystrophy and EL. This combination of autosomal recessive inheritance has not been reported earlier in the literature and suggests a role of connective tissue genes in BFP.

  13. Inherited Pain

    PubMed Central

    Eberhardt, Mirjam; Nakajima, Julika; Klinger, Alexandra B.; Neacsu, Cristian; Hühne, Kathrin; O'Reilly, Andrias O.; Kist, Andreas M.; Lampe, Anne K.; Fischer, Kerstin; Gibson, Jane; Nau, Carla; Winterpacht, Andreas; Lampert, Angelika

    2014-01-01

    Inherited erythromelalgia (IEM) causes debilitating episodic neuropathic pain characterized by burning in the extremities. Inherited “paroxysmal extreme pain disorder” (PEPD) differs in its clinical picture and affects proximal body areas like the rectal, ocular, or jaw regions. Both pain syndromes have been linked to mutations in the voltage-gated sodium channel Nav1.7. Electrophysiological characterization shows that IEM-causing mutations generally enhance activation, whereas mutations leading to PEPD alter fast inactivation. Previously, an A1632E mutation of a patient with overlapping symptoms of IEM and PEPD was reported (Estacion, M., Dib-Hajj, S. D., Benke, P. J., Te Morsche, R. H., Eastman, E. M., Macala, L. J., Drenth, J. P., and Waxman, S. G. (2008) NaV1.7 Gain-of-function mutations as a continuum. A1632E displays physiological changes associated with erythromelalgia and paroxysmal extreme pain disorder mutations and produces symptoms of both disorders. J. Neurosci. 28, 11079–11088), displaying a shift of both activation and fast inactivation. Here, we characterize a new mutation of Nav1.7, A1632T, found in a patient suffering from IEM. Although transfection of A1632T in sensory neurons resulted in hyperexcitability and spontaneous firing of dorsal root ganglia (DRG) neurons, whole-cell patch clamp of transfected HEK cells revealed that Nav1.7 activation was unaltered by the A1632T mutation but that steady-state fast inactivation was shifted to more depolarized potentials. This is a characteristic normally attributed to PEPD-causing mutations. In contrast to the IEM/PEPD crossover mutation A1632E, A1632T failed to slow current decay (i.e. open-state inactivation) and did not increase resurgent currents, which have been suggested to contribute to high-frequency firing in physiological and pathological conditions. Reduced fast inactivation without increased resurgent currents induces symptoms of IEM, not PEPD, in the new Nav1.7 mutation, A1632T

  14. Starving for Recess

    ERIC Educational Resources Information Center

    Patt, Mary Johnson

    2011-01-01

    Every weekday, millions of American schoolchildren throw away their half-eaten cafeteria lunches so that they can run outside to play. The traditional placement of lunch before recess, coupled with the recent decline in overall recess time to meet academic time constraints, forces children to choose between two essential needs: (1) food; and (2)…

  15. Recess Makes Kids Smarter

    ERIC Educational Resources Information Center

    Adams, Caralee

    2011-01-01

    Recess has been scaled back or cut altogether in a number of schools around the country. The trend can be traced back to the late eighties and was accelerated under No Child Left Behind. Districts under pressure to show academic progress began to squeeze as much instruction into the day as possible. Others eliminated recess because of concerns…

  16. More Recess Time, Please!

    ERIC Educational Resources Information Center

    Chang, Rong; Coward, Fanni Liu

    2015-01-01

    Students in Shanghai, China, get much more recess time than their U.S. counterparts throughout their education. As U.S. education reform efforts seek ways of raising achievement, they have begun replacing recess with academic time. The lesson from Shanghai is that this may not be the best strategy. But whether the Shanghai system of more and…

  17. More Recess Time, Please!

    ERIC Educational Resources Information Center

    Chang, Rong; Coward, Fanni Liu

    2015-01-01

    Students in Shanghai, China, get much more recess time than their U.S. counterparts throughout their education. As U.S. education reform efforts seek ways of raising achievement, they have begun replacing recess with academic time. The lesson from Shanghai is that this may not be the best strategy. But whether the Shanghai system of more and…

  18. Starving for Recess

    ERIC Educational Resources Information Center

    Patt, Mary Johnson

    2011-01-01

    Every weekday, millions of American schoolchildren throw away their half-eaten cafeteria lunches so that they can run outside to play. The traditional placement of lunch before recess, coupled with the recent decline in overall recess time to meet academic time constraints, forces children to choose between two essential needs: (1) food; and (2)…

  19. Keeping Recess in Schools

    ERIC Educational Resources Information Center

    Zavacky, Francesca; Michael, Shannon L.

    2017-01-01

    Recess is an important part of a comprehensive school physical activity program by providing physical activity to students during the school day, in addition to physical education and classroom physical activity. Unfortunately, recess in the United States is not an expected part of the school day, especially in middle and high schools. High-stakes…

  20. Recess--It's Indispensable!

    ERIC Educational Resources Information Center

    Jarrett, Olga; Waite-Stupiansky, Sandra

    2009-01-01

    The demise of recess in many elementary schools--and of outdoor play in general--is an issue of great concern to many members of the Play, Policy, and Practice Interest Forum. Most people remember recess as an important part of the school day. It was a time to be outdoors; to organize games; to play on the swings, slides, and other playground…

  1. INHERITED CARDIOMYOPATHIES

    PubMed Central

    Towbin, Jeffrey A.

    2015-01-01

    Cardiomyopathies, diseases of the heart muscle, are major causes of morbidity and mortality. A significant percentage of patients with cardiomyopathies have genetic-based, inheritable disease and, over the past two decades the genetic causes of these disorders have been increasingly discovered. The genes causing these disorders when they are mutated appear to encode proteins that frame a “final common pathway” for that specific disorder but the specifics of the phenotype, including age of onset, severity, and outcome is variable for reasons not yet understood. The “final common pathways” for the classified forms of cardiomyopathy include the sarcomere in the primarily diastolic dysfunction disorders hypertrophic cardiomyopathy (HCM) and restrictive cardiomyopathy (RCM), the linkage of the sarcomere and sarcolemma in the systolic dysfunction disorder dilated cardiomyopathy (DCM), and the desmosome in arrhythmogenic cardiomyopathy (AVC). Left ventricular noncompaction cardiomyopathy (LVNC) is an overlap disorder and appears that any of these “final common pathways” can be involved depending on the specific form of LVNC. The genetics and mechanisms responsible for these clinical phenotypes will be described. PMID:25186923

  2. Autosomal recessive POLR1D mutation with decrease of TCOF1 mRNA is responsible for Treacher Collins syndrome.

    PubMed

    Schaefer, Elise; Collet, Corinne; Genevieve, David; Vincent, Marie; Lohmann, Dietmar R; Sanchez, Elodie; Bolender, Chantal; Eliot, Marie-Madeleine; Nürnberg, Gudrun; Passos-Bueno, Maria-Rita; Wieczorek, Dagmar; van Maldergem, Lionel; Doray, Bérénice

    2014-09-01

    Treacher Collins syndrome is a mandibulofacial dysostosis caused by mutations in genes involved in ribosome biogenesis and synthesis. TCOF1 mutations are observed in ~80% of the patients and are inherited in an autosomal dominant manner. Recently, two other genes have been reported in <2% of patients--POLR1D in patients with autosomal dominant inheritance, and POLR1C in patients with autosomal recessive inheritance. We performed direct sequencing of TCOF1, POLR1C, and POLR1D in two unrelated consanguineous families. The four affected children shared the same homozygous mutation in POLR1D (c.163C>G, p.Leu55Val). This mutation is localized in a region encoding the dimerization domain of the RNA polymerase. It is supposed that this mutation impairs RNA polymerase, resulting in a lower amount of mature dimeric ribosomes. A functional analysis of the transcripts of TCOF1 by real-time quantitative reverse transcription-polymerase chain reaction was performed in the first family, demonstrating a 50% reduction in the index case, compatible with this hypothesis. This is the first report of POLR1D mutation being responsible for an autosomal recessive inherited Treacher Collins syndrome. These results reinforce the concept of genetic heterogeneity of Treacher Collins syndrome and underline the importance of combining clinical expertise and familial molecular analyses for appropriate genetic counseling.

  3. Recessive optic atrophy, sensorimotor neuropathy and cataract associated with novel compound heterozygous mutations in OPA1

    PubMed Central

    LEE, JINHO; JUNG, SUNG-CHUL; HONG, YOUNG BIN; YOO, JEONG HYUN; KOO, HEASOO; LEE, JA HYUN; HONG, HYUN DAE; KIM, SANG-BEOM; CHUNG, KI WHA; CHOI, BYUNG-OK

    2016-01-01

    Mutations in the optic atrophy 1 gene (OPA1) are associated with autosomal dominant optic atrophy and 20% of patients demonstrate extra-ocular manifestations. In addition to these autosomal dominant cases, only a few syndromic cases have been reported thus far with compound heterozygous OPA1 mutations, suggestive of either recessive or semi-dominant patterns of inheritance. The majority of these patients were diagnosed with Behr syndrome, characterized by optic atrophy, ataxia and peripheral neuropathy. The present study describes a 10-year-old boy with Behr syndrome presenting with early-onset severe optic atrophy, sensorimotor neuropathy, ataxia and congenital cataracts. He had optic atrophy and was declared legally blind at six years old. Electrophysiological, radiological, and histopathological findings were compatible with axonal sensorimotor polyneuropathy. At birth, he presented with a congenital cataract, which has not been previously described in patients with OPA1 mutations. Whole exome sequencing indicated a pair of novel compound heterozygous mutations: p.L620fs*13 (c.1857–1858delinsT) and p.R905Q (c.G2714A). Neither mutation was observed in controls (n=300), and thus, they were predicted to be pathogenic by multiple in silico analyses. The mutation sites were highly conserved throughout different vertebrate species. The patients parents did not have any ophthalmic or neurologic symptoms and the results of electrophysiological studies were normal, suggestive of an autosomal recessive pattern of inheritance. The present study identified novel compound heterozygous OPA1 mutations in a patient with recessive optic atrophy, sensorimotor neuropathy and congenital cataracts, indicating an expansion of the clinical spectrum of pathologies associated with OPA1 mutations. Thus, OPA1 gene screening is advisable in the workup of patients with recessive optic atrophy, particularly with Behr syndrome and cataracts. PMID:27150940

  4. Endocardial fibroelastosis: possible X linked inheritance.

    PubMed Central

    Hodgson, S; Child, A; Dyson, M

    1987-01-01

    We report a pedigree in which six males died of cardiac failure within the first eight months of life. These males were related through healthy females, as with X linked recessive inheritance. There was no consanguinity. None of the affected boys had an anatomical cardiac abnormality. In two affected brothers, histological evidence for endomyocardial fibroelastosis was documented, and in one of these electron microscopy demonstrated abnormalities of the mitochondria as found in mitochondrial cytopathy. A review of published reports revealed five similar X linked pedigrees, and in two of these mitochondrial abnormalities were found. We suggest that these families may show an X linked recessive cardiomyopathy with mitochondrial abnormalities. Images PMID:3585935

  5. [Inheritance of notched ears in Highland cattle].

    PubMed

    Scheider, A; Schmidt, P; Distl, O

    1994-10-01

    The present study describes an anomaly of the pinna of the ear and its distribution in Highland Cattle. The investigation is based on a questionnaire survey in farms in Bavaria keeping robust breeds and on registering data in 15 selected farms. In the year 1991, there were registered 548 Highland stud book cows in 108 farms. In four herds animals of the breed Highland Cattle were observed which showed crop ears. Always both ears were affected and this ear defect could be already observed in newborn calves. Crop ears appeared in very different forms. In some cases only small changes of the external ear could be recognized, in more severe cases, grooves in the external ear could be found and in the most severe case, the external ear was totally deformed and drastically reduced in size. In one herd, 45 animals out of the progeny of 46 of one affected breeding bull showed crop ears. The pedigrees indicated that this defect of the ear pinna is inherited and a single autosomal gene with nearly additive (incomplete dominant) action may be involved. Homozygote recessive animals are free from crop ears, animals homozygote for the mutated allele carry totally deformed external ears and heterozygote animals do not show as severe forms of crop ears as homozygote ones.

  6. Inherit Space

    NASA Technical Reports Server (NTRS)

    Giarratano, Joseph C.; Jenks, K. C.

    1997-01-01

    The objective of the proposed research was to begin development of a unique educational tool targeted at educating and inspiring young people 12-16 years old about NASA and the Space Program. Since these young people are the future engineers, scientists and space pioneers, the nurturing of their enthusiasm and interest is of critical importance to the Nation. This summer the basic infrastructure of the tool was developed in the context of an educational game paradigm. The game paradigm has achieved remarkable success in maintaining the interest of young people in a self-paced, student-directed learning environment. This type of environment encourages student exploration and curiosity which are exactly the traits that future space pioneers need to develop to prepare for the unexpected. The Inherit Space Educational Tool is an open-ended learning environment consisting of a finite-state machine classic adventure game paradigm. As the young person explores this world, different obstacles must be overcome. Rewards will be offered such as using the flight simulator to fly around and explore Titan. This simulator was modeled on conventional Earth flight simulators but has been considerably enhanced to add texture mapping of Titan's atmosphere utilizing the latest information from the NASA Galileo Space Probe. Additional scenery was added to provide color VGA graphics of a futuristic research station on Titan as well as an interesting story to keep the youngster's attention. This summer the game infrastructure has been developed as well as the Titan Flight Simulator. A number of other enhancements are planned.

  7. To b = 1 or not to b = 1. Numerical, conceptual, hydraulic and geometric explanations for observed streamflow recession behaviour - a case of being right for which reason?

    NASA Astrophysics Data System (ADS)

    Bogaart, Patrick; Rupp, David; Selker, John; van der Velde, Ype

    2014-05-01

    Recession discharge from hillslopes and catchments is commonly summarized by the top-down Brutsaert and Nieber (1977) analysis in which a power law of the form -dQ/dt = aQb is fitted through recession data. In many cases exponent b is found to be within the range 1 to 2. A key question in hillslope and catchment hydrology is how this range can be explained from underlying bottom-up physical theory and system properties. A common approach in hillslope hydrology is to apply the Boussinesq equation, either in it's original nonlinear form, or a a linearized simplification, in concert with assumptions like thin soils of uniform hydraulic conductivity. We found that the nonlinear Boussinesq equation in this setting leads to b = 0, and thus is inconsistent with observations. Careless interpretation of the recession response from a Boussinesq model could lead to an erroneous conclusion of b = 1. We demonstrate how this artifactual model response arises from the internal numerics of spatially distributed PDE models that hinder complete drying out. We demonstrate how this trait - models that can't dry out - by necessity lead to b ≥ 1 behaviour. Some commonly used model approaches share this trait: As described above, numerical implementations of the nonlinear Boussinesq equation retain the last bits of water, and therefore suggest b = 1 (which is shown to be an artifact) Both analytical and numerical solutions to the linearized Boussinesq equation are unable to move the drainage front downhill (as explained earlier by Stagnitti et al. (2004)), which causes retainment of water, leading to b = 1 at all times. Vertically decreasing hydraulic conductivity, e.g. a power-law or exponential profile, leads to b = 1 to 2. Based on the reasoning that the linearized Boussinesq equation (as a meta-model) is only valid if it adequately mimics the essential dynamics of the nonlinear Boussinesq equation (as a reference model) we conclude that explanations of observed b = 1 based on the

  8. On variants and disease-causing mutations: Case studies of a SEMA4A variant identified in inherited blindness.

    PubMed

    Bryant, Laura; Lozynska, Olga; Han, Grace; Morgan, Jessica I W; Gai, Xiaowu; Maguire, Albert M; Aleman, Tomas; Bennett, Jean

    2017-08-14

    The p.R713Q variant of the semaphorin-4a-encoding gene, SEMA4a, has been reported to cause autosomal dominant retinitis pigmentosa. Here we show three families with retinal degeneration in which unaffected family members are either homozygous or heterozygous for the variant. The p.R713Q variant in SEMA4A is insufficient to cause either autosomal recessive or autosomal dominant retinitis pigmentosa and is unlikely to be pathogenic.

  9. An exome sequencing strategy to diagnose lethal autosomal recessive disorders

    PubMed Central

    Ellard, Sian; Kivuva, Emma; Turnpenny, Peter; Stals, Karen; Johnson, Matthew; Xie, Weijia; Caswell, Richard; Lango Allen, Hana

    2015-01-01

    Rare disorders resulting in prenatal or neonatal death are genetically heterogeneous. For some conditions, affected fetuses can be diagnosed by ultrasound scan, but this is not usually possible until mid-gestation. There is often limited fetal DNA available for investigation. We investigated a strategy for diagnosing autosomal recessive lethal disorders in non-consanguineous pedigrees with multiple affected fetuses. Exome sequencing was performed to identify genes where each parent is heterozygous for a rare non-synonymous-coding or splicing variant. Putative pathogenic variants were tested for cosegregation in affected fetuses and unaffected siblings. In eight couples of European ancestry, we found on average 1.75 genes (range 0–4) where both parents were heterozygous for rare potentially deleterious variants. A proof-of-principle study detected heterozygous DYNC2H1 variants in a couple whose five fetuses had short-rib polydactyly. Prospective analysis of two couples with multiple pregnancy terminations for fetal akinesia syndrome was performed and a diagnosis was obtained in both the families. The first couple were each heterozygous for a previously reported GLE1 variant, p.Arg569His or p.Val617Met; both were inherited by their two affected fetuses. The second couple were each heterozygous for a novel RYR1 variant, c.14130-2A>G or p.Ser3074Phe; both were inherited by their three affected fetuses but not by their unaffected child. Biallelic GLE1 and RYR1 disease-causing variants have been described in other cases with fetal akinesia syndrome. We conclude that exome sequencing of parental samples can be an effective tool for diagnosing lethal recessive disorders in outbred couples. This permits early prenatal diagnosis in future pregnancies. PMID:24961629

  10. An exome sequencing strategy to diagnose lethal autosomal recessive disorders.

    PubMed

    Ellard, Sian; Kivuva, Emma; Turnpenny, Peter; Stals, Karen; Johnson, Matthew; Xie, Weijia; Caswell, Richard; Lango Allen, Hana

    2015-03-01

    Rare disorders resulting in prenatal or neonatal death are genetically heterogeneous. For some conditions, affected fetuses can be diagnosed by ultrasound scan, but this is not usually possible until mid-gestation. There is often limited fetal DNA available for investigation. We investigated a strategy for diagnosing autosomal recessive lethal disorders in non-consanguineous pedigrees with multiple affected fetuses. Exome sequencing was performed to identify genes where each parent is heterozygous for a rare non-synonymous-coding or splicing variant. Putative pathogenic variants were tested for cosegregation in affected fetuses and unaffected siblings. In eight couples of European ancestry, we found on average 1.75 genes (range 0-4) where both parents were heterozygous for rare potentially deleterious variants. A proof-of-principle study detected heterozygous DYNC2H1 variants in a couple whose five fetuses had short-rib polydactyly. Prospective analysis of two couples with multiple pregnancy terminations for fetal akinesia syndrome was performed and a diagnosis was obtained in both the families. The first couple were each heterozygous for a previously reported GLE1 variant, p.Arg569His or p.Val617Met; both were inherited by their two affected fetuses. The second couple were each heterozygous for a novel RYR1 variant, c.14130-2A>G or p.Ser3074Phe; both were inherited by their three affected fetuses but not by their unaffected child. Biallelic GLE1 and RYR1 disease-causing variants have been described in other cases with fetal akinesia syndrome. We conclude that exome sequencing of parental samples can be an effective tool for diagnosing lethal recessive disorders in outbred couples. This permits early prenatal diagnosis in future pregnancies.

  11. Fryns Syndrome Associated with Recessive Mutations in PIGN in two Separate Families.

    PubMed

    McInerney-Leo, Aideen M; Harris, Jessica E; Gattas, Michael; Peach, Elizabeth E; Sinnott, Stephen; Dudding-Byth, Tracy; Rajagopalan, Sulekha; Barnett, Christopher P; Anderson, Lisa K; Wheeler, Lawrie; Brown, Matthew A; Leo, Paul J; Wicking, Carol; Duncan, Emma L

    2016-07-01

    Fryns syndrome is an autosomal recessive condition characterized by congenital diaphragmatic hernia (CDH), dysmorphic facial features, distal digital hypoplasia, and other associated malformations, and is the most common syndromic form of CDH. No gene has been associated with this condition. Whole-exome sequence data from two siblings and three unrelated individuals with Fryns syndrome were filtered for rare, good quality, coding mutations fitting a recessive inheritance model. Compound heterozygous mutations in PIGN were identified in the siblings, with appropriate parental segregation: a novel STOP mutation (c.1966C>T: p.Glu656X) and a rare (minor allele frequency <0.001) donor splice site mutation (c.1674+1G>C) causing skipping of exon 18 and utilization of a cryptic acceptor site in exon 19. A further novel homozygous STOP mutation in PIGN (c.694A>T: p.Lys232X) was detected in one unrelated case. All three variants affected highly conserved bases. The two remaining cases were negative for PIGN mutations. Mutations in PIGN have been reported in cases with multiple congenital anomalies, including one case with syndromic CDH. Fryns syndrome can be caused by recessive mutations in PIGN. Whether PIGN affects other syndromic and non-syndromic forms of CDH warrants investigation.

  12. [Gene therapy for inherited retinal dystrophies].

    PubMed

    Côco, Monique; Han, Sang Won; Sallum, Juliana Maria Ferraz

    2009-01-01

    The inherited retinal dystrophies comprise a large number of disorders characterized by a slow and progressive retinal degeneration. They are the result of mutations in genes that express in either the photoreceptor cells or the retinal pigment epithelium. The mode of inheritance can be autosomal dominant, autosomal recessive, X linked recessive, digenic or mitochondrial DNA inherited. At the moment, there is no treatment for these conditions and the patients can expect a progressive loss of vision. Accurate genetic counseling and support for rehabilitation are indicated. Research into the molecular and genetic basis of disease is continually expanding and improving the prospects for rational treatments. In this way, gene therapy, defined as the introduction of exogenous genetic material into human cells for therapeutic purposes, may ultimately offer the greatest treatment for the inherited retinal dystrophies. The eye is an attractive target for gene therapy because of its accessibility, immune privilege and translucent media. A number of retinal diseases affecting the eye have known gene defects. Besides, there is a well characterized animal model for many of these conditions. Proposals for clinical trials of gene therapy for inherited retinal degenerations owing to defects in the gene RPE65, have recently received ethical approval and the obtained preliminary results brought large prospects in the improvement on patient's quality of life.

  13. Genetics beyond Mendel. Understanding nontraditional inheritance patterns.

    PubMed

    Wagstaff, J

    2000-09-01

    Many medical conditions that clearly have a strong genetic component are not transmitted in a straightforward dominant, recessive, or X-linked pattern. Recent progress in understanding other modes of inheritance, such as imprinting, trinucleotide repeat expansion, mitochondrial inheritance, and mosaicism, has allowed us to solve many of these hereditary puzzles. Such advances have led to improvements in diagnosis and genetic counseling for patients affected with these disorders and should be valuable in development of effective therapies for some of these disorders in the future.

  14. Autosomal recessive congenital stenosis of aqueduct of Sylvius.

    PubMed

    Barros-Nuñes, P; Rivas, F

    1993-01-01

    Congenital hydrocephalus is an etiologically heterogeneous central nervous system malformation. Mendelian inheritance of stenosis of the aqueduct of Sylvius (SAS) accounts for almost 2% of all nonsyndromic forms. Among the monogenetic forms the great majority are X-linked. In this report we describe autosomal recessive transmission of SAS hydrocephalus in a high consanguinity family.

  15. A case report of Chinese brothers with inherited MECP2-containing duplication: autism and intellectual disability, but not seizures or respiratory infections

    PubMed Central

    2012-01-01

    Background Autistic spectrum disorders (ASDs) are a family of neurodevelopmental disorders with strong genetic components. Recent studies have shown that copy number variations in dosage sensitive genes can contribute significantly to these disorders. One such gene is the transcription factor MECP2, whose loss of function in females results in Rett syndrome, while its duplication in males results in developmental delay and autism. Case presentation Here, we identified a Chinese family with two brothers both inheriting a 2.2 Mb MECP2-containing duplication (151,369,305 – 153,589,577) from their mother. In addition, both brothers also had a 213.7 kb duplication on Chromosome 2, inherited from their father. The older brother also carried a 48.4 kb duplication on Chromosome 2 inherited from the mother, and a 8.2 kb deletion at 11q13.5 inherited from the father. Based on the published literature, MECP2 is the most autism-associated gene among the identified CNVs. Consistently, the boys displayed clinical features in common with other patients carrying MECP2 duplications, including intellectual disability, autism, lack of speech, slight hypotonia and unsteadiness of movement. They also had slight dysmorphic features including a depressed nose bridge, large ears and midface hypoplasia. Interestingly, they did not exhibit other clinical features commonly observed in American-European patients with MECP2 duplication, including recurrent respiratory infections and epilepsy. Conclusions To our knowledge, this is the first identification and characterization of Chinese Han patients with MECP2-containing duplications. Further cases are required to determine if the above described clinical differences are due to individual variations or related to the genetic background of the patients. PMID:22909152

  16. [Autosomal recessive cerebellar ataxias].

    PubMed

    Tranchant, Christine; Anheim, Mathieu

    2009-12-01

    Friedreich ataxia is the most frequent recessive cerebral ataxia d should always be researched first. Ataxia with isolated vitamin E deficiency and abetalipoproteinemia have a specific treatment. Associated neurological signs such polyneuroapthy, ophtalmologic or oculomotor signs, pyramidal signs, and cerebellar MRI can lead to the etiological diagnosis. Biological tests should be: vitamin E, cholesterol, alpha-fetoprotein levels, acanthocytes, than phytanic acid, cholestanol, lysosomal enzymes. Numerous autosomal recessive cerebellar ataxia remain without etiology.

  17. Inherited hepatocellular carcinoma.

    PubMed

    Villanueva, Augusto; Newell, Pippa; Hoshida, Yujin

    2010-10-01

    Inherited liver disorders that cause chronic inflammation, fibrosis, and cirrhosis can lead to the development of liver cancer. Because of the rarity and diversity of some of these syndromes, the relative risk of developing HCC in these patients and the age at which tumours typically arise cannot be accurately estimated. Among patients with hereditary hemachromatosis (HH), the annual incidence of HCC is 4% once cirrhosis has been established. Fibrosis and portal hypertension associated with HH can be partially reversed with therapeutic phlebotomy, but it is unclear whether this treatment alters the incidence of HCC in these patients. Importantly, it seems likely that coincidence of these genetic disorders with known HCC risk factors such as alcoholism and viral hepatitis would amplify their oncogenic potential. For this reason, patients with known genetic disorders of the liver should be repeatedly counselled to avoid environmental and toxic injury to the liver. Treatment of HCC in patients with inherited liver disease mirrors that of HCC associated with other etiologies. Unfortunately, there are case series which suggest these patients with inherited liver disease and HCC tend to present at more advanced stages and are therefore not eligible for curative therapies, causing overall decreased survival relative to patients with HCC of viral or other etiologies. Copyright © 2010 Elsevier Ltd. All rights reserved.

  18. On estimation and identifiability issues of sex-linked inheritance with a case study of pigmentation in Swiss barn owl (Tyto alba).

    PubMed

    Larsen, Camilla T; Holand, Anna M; Jensen, Henrik; Steinsland, Ingelin; Roulin, Alexandre

    2014-05-01

    Genetic evaluation using animal models or pedigree-based models generally assume only autosomal inheritance. Bayesian animal models provide a flexible framework for genetic evaluation, and we show how the model readily can accommodate situations where the trait of interest is influenced by both autosomal and sex-linked inheritance. This allows for simultaneous calculation of autosomal and sex-chromosomal additive genetic effects. Inferences were performed using integrated nested Laplace approximations (INLA), a nonsampling-based Bayesian inference methodology. We provide a detailed description of how to calculate the inverse of the X- or Z-chromosomal additive genetic relationship matrix, needed for inference. The case study of eumelanic spot diameter in a Swiss barn owl (Tyto alba) population shows that this trait is substantially influenced by variation in genes on the Z-chromosome ([Formula: see text] and [Formula: see text]). Further, a simulation study for this study system shows that the animal model accounting for both autosomal and sex-chromosome-linked inheritance is identifiable, that is, the two effects can be distinguished, and provides accurate inference on the variance components.

  19. Autozygosity mapping of autosomal recessive non-syndromic sensorineural hearing loss (ARNSSNHL)

    SciTech Connect

    Brown, K.A.; Nobel, A.; Markham, A.F.

    1994-09-01

    Congenital deafness affects about 1 in 2000 persons and is of genetic origin in approximately half these cases. The majority of congenital deafness is non-syndromic and over 75% of cases are compatible with autosomal recessive inheritance. Mapping of the loci responsible for ARNSSNHL will be complicated by genetic heterogeneity. Our approach to isolating genes involved in ARNSSNHL is by autozygosity mapping which involves the genetic analysis of children resulting from consanguineous marriages with the aim of identifying regions of homozygosity unique to the genomes of affected individuals which have been inherited from a common ancestor. The population employed in this study is the Pakistani community of Leeds, Bradford and Manchester in the UK which originated from the Mirpur region of Pakistan. Microsatellite analysis of the genome with markers spaced, on average, 10 cM apart is in progress and the investigation of 15 consanguineous families has identified one family which shows linkage to human chromosome 13q. This family appears to be linked to the same autosomal recessive deafness locus as two Tunisian families recently described and confirms that this chromosome 13q locus is also responsible, although as a minor contributor, to the deafness observed in the Pakistani population.

  20. Scalp-Ear-Nipple Syndrome: A Case Report

    PubMed Central

    Morales-Peralta, Estela; Andrés, Vivian; Campillo Betancourt, Dainé

    2014-01-01

    The scalp-ear-nipple (SEN) syndrome is an infrequent congenital disease. Its main features are scalp defects, malformed ears, and absence of nipples. Most of the reported cases are autosomal dominant. We report on a patient suffering SEN syndrome with possible autosomal recessive inheritance. It is concluded that SEN syndrome should be recognized as an entity with genetic heterogeneity once there is evidence of different genetic manner of inheritance described in this disease. PMID:24660003

  1. [Inheritance of psoriasis. Analysis of 2035 family histories].

    PubMed

    Andressen, C; Henseler, T

    1982-04-01

    Detailed pedigrees were established in 2,035 families with psoriasis, including 30 twin pairs, and evaluated by means of computer analysis. The following results on the devolution of psoriasis were drawn: the hypotheses of the irregular dominant and the bifactorial recessive inheritance appear to be inacceptable. The findings suggest a multifactorial etiology of psoriasis with a polygenic mode of inheritance. The risk for relatives to be affected by psoriasis is calculated.

  2. Pathology of inherited rickets in Corriedale sheep.

    PubMed

    Dittmer, K E; Thompson, K G; Blair, H T

    2009-01-01

    A skeletal disease with features of rickets and simple autosomal recessive inheritance has been discovered in Corriedale sheep in New Zealand. The clinical signs resemble rickets in other species and include decreased growth rate, thoracic lordosis and angular limb deformities. Gross lesions include segmental thickening of physes, growth arrest lines, collapse of subchondral bone of the humeral head, thickened cortices and enthesophytes around distal limb joints. Microscopically, there is persistence of hypertrophic chondrocytes at sites of endochondral ossification, inappropriate and excessive osteoclastic resorption, microfractures and wide, unmineralized osteoid seams lining trabeculae and filling secondary osteons. This study confirms that this skeletal disease of Corriedale sheep is a newly discovered form of inherited rickets and suggests that the genetic defect may be different from inherited forms of rickets described to date in man and animals.

  3. A Case Series: Congenital Hyperinsulinism

    PubMed Central

    Alaei, Mohammad Reza; Akbaroghli, Susan; Keramatipour, Mohammad; Alaei, Ali

    2016-01-01

    Introduction Congenital hyperinsulinism is a rare inherited disease caused by mutations in genes responsible for β-cell’s function in glucose hemostasis leading to profound and recurrent hypoglycemia. The incidence of the disease is about 1 in 50000 newborns. Mutations in at least 8 genes have been reported to cause congenital hyperinsulinism. Mutations in ABCC8 gene are the most common cause of the disease that account for approximately 40% of cases. Less frequently KCNJ11 gene mutations are responsible for the disease. Mutations in other genes such as HADH account for smaller fractions of cases. In nearly half of the cases the cause remains unknown. Case Presentation During the period between 2005 and 2010, a total of six patients with persistent hyperinsulinism were investigated at Mofid Children’s Hospital. In this study all of the patients had early onset hyperinsulinemia. Five patients had consanguineous parents. After failure of medical treatment in three patients, They were undergone pancreatectomy. Two diffuse types and one focal type had been recognized in pathological analysis of intra-operative frozen specimens of pancreas in these patients. Genetic analysis was performed using polymerase chain reaction followed by Sanger sequencing for ABCC8, KCNJ11and HADH genes. In five patients homozygous mutations in these genes were identified that indicated an autosomal recessive pattern of inheritance. In one patient a heterozygous mutation in ABCC8 was identified, indicating possible autosomal dominant inheritance of the disease. Conclusions Congenital hyperinsulinism can have different inheritance pattern. Autosomal recessive inheritance is more common but less frequently autosomal dominant inheritance can be seen. It appears that mutations in ABCC8 gene can show both autosomal recessive and autosomal dominant inheritance of the disease. PCR followed by Sanger sequencing proved to be an efficient method for mutation detection in three investigated genes

  4. Recessive dystrophic epidermolysis bullosa: case of non-Hallopeau-Siemens variant with premature termination codons in both alleles.

    PubMed

    Yonei, Nozomi; Ohtani, Toshio; Furukawa, Fukumi

    2006-11-01

    Dystrophic epidermolysis bullosa (DEB) is caused by mutations in the COL7A1 gene encoding collagen, the major component of anchoring fibrils. Premature termination codon (PTC) mutations in both alleles usually lead to the Hallopeau-Siemens variant that shows the most severe phenotype. We experienced a case of the non-Hallopeau-Siemens variant (nHS-RDEB), which had a mild clinical severity although it has PTC mutations in both alleles. Our patient was a compound heterozygote for a nonsense mutation (R669X) in exon 15 and a nonsense mutation (E2857X) in exon 116. But we confirmed the existence of some anchoring fibrils on electron micrograph. This suggested that a PTC close to the 3' end of COL7A1 does not completely abolish the collagen VII mRNA. We hypothesized that the truncated procollagen VII from the mutant allele with a nonsense mutation (E2857X) in exon 116 included two out of eight cysteines needed for disulfide bond formation, and hence a few functional anchoring fibrils could be formed.

  5. The Recess Renaissance

    ERIC Educational Resources Information Center

    Keeler, Rusty

    2015-01-01

    The author tells of his work around the country and world on transforming how schools do recess, free play, and outside time by transforming their outdoor spaces to match. Instead of a playground of fixed structures like traditional school grounds, newer spaces are filled with loose materials that children can use to build forts, dens, and tree…

  6. The Recess Renaissance

    ERIC Educational Resources Information Center

    Keeler, Rusty

    2015-01-01

    The author tells of his work around the country and world on transforming how schools do recess, free play, and outside time by transforming their outdoor spaces to match. Instead of a playground of fixed structures like traditional school grounds, newer spaces are filled with loose materials that children can use to build forts, dens, and tree…

  7. Virological analysis of inherited chromosomally integrated human herpesvirus-6 in three hematopoietic stem cell transplant patients.

    PubMed

    Miura, H; Kawamura, Y; Kudo, K; Ihira, M; Ohye, T; Kurahashi, H; Kawashima, N; Miyamura, K; Yoshida, N; Kato, K; Takahashi, Y; Kojima, S; Yoshikawa, T

    2015-10-01

    We analyzed 3 hematopoietic stem cell transplant (HSCT) recipients with inherited chromosomally integrated human herpesvirus-6 (inherited CIHHV-6). Cases 1 (inherited CIHHV-6A) and 2 (inherited CIHHV-6B) were inherited CIHHV-6 recipients. Case 3 received bone marrow from a donor with inherited CIHHV-6B. Following HSCT, HHV-6B was isolated from Case 1. HHV-6A and -6B messenger RNAs were detected in Cases 1 and 3.

  8. On the minimally invasive approach to the gingival recession

    PubMed Central

    Jargin, Sergei V.

    2013-01-01

    Some aspects of pathogenesis and therapeutic approach to the gingival recession are discussed in this short communication with the example of a typical case from Russia, where excessive socket curettage after a tooth extraction resulted in a marked gingival recession. Subgingival plaque and calculus can be secondary to recession. An argument about plaque as a source of microorganisms might be plausible in case of inflammation, although various microorganisms are normal for the oral cavity. From the viewpoint of general pathology, being an atrophic condition, recession can progress due to repeated damage. On the author's opinion, calculus removal is not indicated at least for aged patients with marked gingival recession, having modest esthetic demands. Socket curettage after exodontia should be gentle. Surgical treatment of the gingival recession is beyond the scope of this communication. PMID:24049345

  9. Autosomal recessive Charcot-Marie-Tooth disease: from genes to phenotypes.

    PubMed

    Tazir, Meriem; Bellatache, Mounia; Nouioua, Sonia; Vallat, Jean-Michel

    2013-06-01

    The prevalence of Charcot-Marie-Tooth (CMT) disease or hereditary motor and sensory neuropathy (HMSN) varies in different populations. While in some countries of Western Europe, the United States and Japan the dominant form of HMSN is the most frequent, in other countries such as those of the Mediterranean Basin, the autosomal recessive form (AR-CMT) is more common. Autosomal recessive CMT cases are generally characterized by earlier onset, usually before the age of 2 or 3 years, and rapid clinical progression that results in severe polyneuropathy and more marked distal limb deformities such as pes equino-varus, claw-like hands, and often major spinal deformities. Recent clinical, morphological and molecular investigations of CMT families with autosomal recessive inheritance allowed the identification of many genes such as GDAP1, MTMR2, SBF2, NDRG1, EGR2, SH3TC2, PRX, FGD4, and FIG4, implicated in demyelinating forms (ARCMT1 or CMT4), and LMNA, MED25, HINT1, GDAP1, LRSAM1, NEFL, HSPB1 and MFN2 in axonal forms (ARCMT2). However, many patients remain without genetic diagnosis to date, prompting investigations into ARCMT families in order to help discover new genes and common pathways. This review summarizes recent advances regarding the genotypes and corresponding phenotypes of AR-CMT.

  10. The application of next-generation sequencing in the autozygosity mapping of human recessive diseases.

    PubMed

    Alkuraya, Fowzan S

    2013-11-01

    Autozygosity, or the inheritance of two copies of an ancestral allele, has the potential to not only reveal phenotypes caused by biallelic mutations in autosomal recessive genes, but to also facilitate the mapping of such mutations by flagging the surrounding haplotypes as tractable runs of homozygosity (ROH), a process known as autozygosity mapping. Since SNPs replaced microsatellites as markers for the purpose of genomewide identification of ROH, autozygosity mapping of Mendelian genes has witnessed a significant acceleration. Historically, successful mapping traditionally required favorable family structure that permits the identification of an autozygous interval that is amenable to candidate gene selection and confirmation by Sanger sequencing. This requirement presented a major bottleneck that hindered the utilization of simplex cases and many multiplex families with autosomal recessive phenotypes. However, the advent of next-generation sequencing that enables massively parallel sequencing of DNA has largely bypassed this bottleneck and thus ushered in an era of unprecedented pace of Mendelian disease gene discovery. The ability to identify a single causal mutation among a massive number of variants that are uncovered by next-generation sequencing can be challenging, but applying autozygosity as a filter can greatly enhance the enrichment process and its throughput. This review will discuss the power of combining the best of both techniques in the mapping of recessive disease genes and offer some tips to troubleshoot potential limitations.

  11. What Is a Recessive Allele?

    ERIC Educational Resources Information Center

    American Biology Teacher, 1991

    1991-01-01

    Presents four misconceptions students have concerning the concepts of recessive and dominant alleles. Discusses the spectrum of dominant-recessive relationships, different levels of analysis between phenotype and genotype, possible causes of dominance, and an example involving wrinkled peas. (MDH)

  12. What Is a Recessive Allele?

    ERIC Educational Resources Information Center

    American Biology Teacher, 1991

    1991-01-01

    Presents four misconceptions students have concerning the concepts of recessive and dominant alleles. Discusses the spectrum of dominant-recessive relationships, different levels of analysis between phenotype and genotype, possible causes of dominance, and an example involving wrinkled peas. (MDH)

  13. Use of Allograft with Platelet Concentrate in the Treatment of Multiple Miller Class III Gingival Recession Defects: Report of Three Cases.

    PubMed

    Ogata, Yumi; Bui, Minh; Griffin, Terrence J; Hur, Yong

    Three patients with multiple Miller Class III recession defects with substantial bone loss were treated with hard tissue augmentation with the goal to prevent future recessions. The surgery involved a full-thickness mucoperiosteal coronally advanced flap, bone grafting, and primary flap closure. Freeze-dried bone allograft (FDBA) in combination with plasma rich in growth factors (PRGF) was grafted during the procedure. After more than 6 months, the treated sites showed soft tissue maturation and esthetic tissue blending. Clinically, an increase in convexity of alveolar ridge and soft tissue was observed, as well as a marked reduction in recession depth and gain in width of keratinized mucosa. Cone beam computed tomography showed a gain in buccal bone thickness. The use of FDBA in combination with PRGF appears to have potential for the treatment of Miller Class III defects by providing improved hard and soft tissue profiles.

  14. Treatment of multiple adjacent maxillary Miller Class I, II, and III gingival recessions with the modified coronally advanced tunnel, enamel matrix derivative, and subepithelial connective tissue graft: A report of 12 cases.

    PubMed

    Sculean, Anton; Cosgarea, Raluca; Stähli, Alexana; Katsaros, Christos; Arweiler, Nicole Birgit; Miron, Richard John; Deppe, Herbert

    2016-01-01

    To clinically evaluate the healing of multiple adjacent maxillary Miller Class I, II, and III gingival recessions (MAGR) treated with the modified coronally advanced tunnel (MCAT) in conjunction with an enamel matrix derivative (EMD) and subepithelial connective tissue graft (SCTG). Twelve systemically healthy patients (6 females) with a total of 54 adjacent maxillary Miller Class I, II, or III MAGR were consecutively treated with MCAT in conjunction with EMD and SCTG. Out of the 54 recessions, 44 were classified as Miller Class I, five as Miller Class II, and five as Miller Class III. Patients were included in the study if they presented at least two adjacent recessions with a depth of ≥ 3 mm. Measurements were made at baseline (immediately before reconstructive surgery) and at 12 months postoperatively. The primary outcome variable was complete root coverage (CRC) (ie, 100% root coverage). Healing was uneventful in all cases without any complications such as postoperative bleeding, allergic reactions, abscesses, or loss of SCTG. At 12 months, statistically highly significant (P < .0001) root coverage was obtained in all patients and recessions. CRC was obtained in 37 Miller Class I, three Miller Class II, and one Miller Class III recessions, respectively. Mean root coverage was 96%. Mean keratinized tissue width increased statistically highly significantly (P < .004) from 2.04 ± 0.95 mm at baseline to 2.37 ± 0.89 mm at 12 months. The present findings indicate that the proposed treatment concept results in predictable coverage of multiple adjacent maxillary Miller Class I, II, and III MAGR.

  15. School Recess and Social Development.

    ERIC Educational Resources Information Center

    Jambor, Tom

    1994-01-01

    Discusses the role of school recess periods in children's social development and academic achievement. Also examines changing attitudes toward the use of recess periods in the United States and other nations, and presents strategies for classroom teachers to use in advocating school recess periods in their schools and communities. (MDM)

  16. Mitochondrial inheritance in fungi.

    PubMed

    Basse, Christoph W

    2010-12-01

    Faithful inheritance of mitochondria is essential for growth and development. Uniparental inheritance of mitochondria is a common phenomenon in sexual eukaryotes and has been reported for numerous fungal species. Uniparental inheritance is a genetically regulated process, aimed to gain a homoplasmic state within cells, and this is often associated with selective elimination of one parental mitochondria population. This review will focus on recent developments in our understanding of common and specified regulatory circuits of selective mitochondrial inheritance during sexual development. It further refers to the influence of mitochondrial fusion on generation of recombinant mitochondrial DNA molecules. The latter aspect appears rather exciting in the context of intron homing and could bring a new twist to the debate on the significance of uniparental inheritance. The emergence of genome-wide studies offers new perspectives to address potential relationships between uniparental inheritance, vegetative inheritance and last but not least cellular scavenging systems to dispose of disintegrated organelles.

  17. An asbestos-exposed family with multiple cases of pleural malignant mesothelioma without inheritance of a predisposing BAP1 mutation.

    PubMed

    Cheung, Mitchell; Kadariya, Yuwaraj; Pei, Jianming; Talarchek, Jacqueline; Facciolo, Francesco; Visca, Paolo; Righi, Luisella; Cozzi, Ilaria; Testa, Joseph R; Ascoli, Valeria

    2015-10-01

    We report a family with domestic exposure to asbestos and diagnosis of multiple cancers, including eight pleural malignant mesotheliomas and several other lung or pleural tumors. DNA sequence analysis revealed no evidence for an inherited mutation of BAP1. Sequence analysis of other potentially relevant genes, including TP53, CDKN2A, and BARD1, also revealed no mutation. DNA microarray analysis of tissue from two mesotheliomas revealed multiple genomic imbalances, including consistent losses of overlapping segments in 2q, 6q, 9p, 14q, 15q, and 22q, but no losses of chromosome 3 harboring the BAP1 locus. However, the results of immunohistochemical analysis demonstrated loss of nuclear BAP1 staining in three of six mesotheliomas tested, suggesting that somatic alterations of BAP1 occurred in a subset of tumors from this family. Since mesothelioma could be confirmed in only a single generation, domestic exposure to asbestos may be the predominant cause of mesothelioma in this family. Given the existence of unspecified malignant pleural tumors and lung cancers in a prior generation, we discuss the possibility that some other tumor susceptibility or modifier gene(s) may contribute to the high incidence of mesothelioma in this family. Because the incidence of mesothelioma in this family is higher than that expected even in workers heavily exposed to asbestos, we conclude that both asbestos exposure and genetic factors have played a role in the high rate of mesothelioma and potentially other pleural or lung cancers seen in this family. 

  18. The impact of the Great Recession on mental health and its inequalities: the case of a Southern European region, 1997-2013.

    PubMed

    Bacigalupe, Amaia; Esnaola, Santiago; Martín, Unai

    2016-01-26

    Numerous studies have shown that macroeconomic changes have a great influence on health, prompting different concerns in recent literature about the effects of the current recession. The objective of the study was to assess the changes in the mental health of the working-age population in the Basque Country (Spain) and its social inequalities following the onset of the 2008 recession, with special focus on the role of unemployment. Repeated cross-sectional study on the population aged 16-64, using four Basque Health Surveys (1997-2013). Age-adjusted prevalences of poor mental health and incremental prevalence ratios (working status and social class adjusted) between years were calculated. Absolute/relative measures of social inequalities were also calculated. From 2008, there was a clear deterioration in the mental health, especially among men. Neither changes in employment status nor social class accounted for these changes. In men, the deterioration affected all working status categories, except the retired but significant changes occurred only among the employed. In women, poor mental health significantly increased among the unemployed. Students were also especially affected. Relative inequalities increased only in men. The Great Recession is being accompanied by adverse effects on mental health, which cannot be fully explained by the increase of unemployment. Public health professionals should closely monitor the medium and long-term effects of the crisis as these may emerge only many years after the onset of recessions.

  19. The myotubular myopathies: differential diagnosis of the X linked recessive, autosomal dominant, and autosomal recessive forms and present state of DNA studies.

    PubMed Central

    Wallgren-Pettersson, C; Clarke, A; Samson, F; Fardeau, M; Dubowitz, V; Moser, H; Grimm, T; Barohn, R J; Barth, P G

    1995-01-01

    Clinical differences exist between the three forms of myotubular myopathy. They differ regarding age at onset, severity of the disease, and prognosis, and also regarding some of the clinical characteristics. The autosomal dominant form mostly has a later onset and milder course than the X linked form, and the autosomal recessive form is intermediate in both respects. These differences are, however, quantitative rather than qualitative. Muscle biopsy studies of family members are useful in some cases, and immunohistochemical staining of desmin and vimentin may help distinguish between the X linked and autosomal forms. Determining the mode of inheritance and prognosis in individual families, especially those with a single male patient, still poses a problem. Current molecular genetic results indicate that the gene for the X linked form is located in the proximal Xq28 region. Further molecular genetic studies are needed to examine the existence of genetic heterogeneity in myotubular myopathy and to facilitate diagnosis. Images PMID:8544184

  20. Inherited mitochondrial optic neuropathies

    PubMed Central

    Yu-Wai-Man, P; Griffiths, P G; Hudson, G; Chinnery, P F

    2009-01-01

    Leber hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (DOA) are the two most common inherited optic neuropathies and they result in significant visual morbidity among young adults. Both disorders are the result of mitochondrial dysfunction: LHON from primary mitochondrial DNA (mtDNA) mutations affecting the respiratory chain complexes; and the majority of DOA families have mutations in the OPA1 gene, which codes for an inner mitochondrial membrane protein critical for mtDNA maintenance and oxidative phosphorylation. Additional genetic and environmental factors modulate the penetrance of LHON, and the same is likely to be the case for DOA which has a markedly variable clinical phenotype. The selective vulnerability of retinal ganglion cells (RGCs) is a key pathological feature and understanding the fundamental mechanisms that underlie RGC loss in these disorders is a prerequisite for the development of effective therapeutic strategies which are currently limited. PMID:19001017

  1. Recessive versus imprinted disorder: consanguinity can impede establishing the diagnosis of autosomal dominant pseudohypoparathyroidism type Ib

    PubMed Central

    Turan, Serap; Akin, Leyla; Akcay, Teoman; Adal, Erdal; Sarikaya, Sevil; Bastepe, Murat; Jüppner, Harald

    2010-01-01

    Hypocalcemia and hyperphosphatemia with low/normal parathyroid hormone (PTH) levels can be observed in hypoparathyroidism (HP), a disorder that may follow an autosomal dominant (AD) or autosomal recessive (AR) mode of inheritance. Similar biochemical changes are also observed in pseudohypoparathyroidism (PHP) type Ia and Ib, but affected patients usually show elevated PTH levels indicative of hormonal resistance. Features of Albright’s hereditary osteodystrophy (AHO) are typically not observed in patients affected by familial forms of PHP-Ib, which are most frequently caused by maternally inherited, heterozygous microdeletions within STX16 and are associated with isolated loss of methylation at GNAS exon A/B. We established the molecular defect in two children of consanguineous Turkish parents, who presented with hypocalcemia, hyperphosphatemia, and low 25-OH vitamin D levels, but initially normal or only mildly elevated PTH levels, i.e. findings that do not readily exclude HP. After normalizing serum magnesium levels, hypocalcemia and hyperphosphatemia persisted, and PTH levels increased, suggesting PTH-resistance rather than PTH-deficiency. Because of the absence of AHO and parental consanguinity, an AR form of PHP-Ib appeared plausible, which had previously been suggested for sporadic cases. However, loss of GNAS methylation was restricted to exon A/B, which led to the identification of the 3-kb STX16 microdeletion. The same mutation was also detected in the healthy mother, who did not show any GNAS methylation abnormality, indicating that her deletion resides on the paternal allele. Our findings emphasize the importance of considering a parentally imprinted, autosomal dominant disorder even if consanguinity suggests an autosomal recessive mode of inheritance. PMID:20538864

  2. Recessive truncating titin gene, TTN, mutations presenting as centronuclear myopathy

    PubMed Central

    Ceyhan-Birsoy, Ozge; Agrawal, Pankaj B.; Hidalgo, Carlos; Schmitz-Abe, Klaus; DeChene, Elizabeth T.; Swanson, Lindsay C.; Soemedi, Rachel; Vasli, Nasim; Iannaccone, Susan T.; Shieh, Perry B.; Shur, Natasha; Dennison, Jane M.; Lawlor, Michael W.; Laporte, Jocelyn; Markianos, Kyriacos; Fairbrother, William G.; Granzier, Henk

    2013-01-01

    Objective: To identify causative genes for centronuclear myopathies (CNM), a heterogeneous group of rare inherited muscle disorders that often present in infancy or early life with weakness and hypotonia, using next-generation sequencing of whole exomes and genomes. Methods: Whole-exome or -genome sequencing was performed in a cohort of 29 unrelated patients with clinicopathologic diagnoses of CNM or related myopathy depleted for cases with mutations of MTM1, DNM2, and BIN1. Immunofluorescence analyses on muscle biopsies, splicing assays, and gel electrophoresis of patient muscle proteins were performed to determine the molecular consequences of mutations of interest. Results: Autosomal recessive compound heterozygous truncating mutations of the titin gene, TTN, were identified in 5 individuals. Biochemical analyses demonstrated increased titin degradation and truncated titin proteins in patient muscles, establishing the impact of the mutations. Conclusions: Our study identifies truncating TTN mutations as a cause of congenital myopathy that is reported as CNM. Unlike the classic CNM genes that are all involved in excitation-contraction coupling at the triad, TTN encodes the giant sarcomeric protein titin, which forms a myofibrillar backbone for the components of the contractile machinery. This study expands the phenotypic spectrum associated with TTN mutations and indicates that TTN mutation analysis should be considered in cases of possible CNM without mutations in the classic CNM genes. PMID:23975875

  3. Genetic linkage studies in autosomal recessive retinitis pigmentosa

    SciTech Connect

    Mansfield, D.C.; Teague, P.W.; Barber, A.

    1994-09-01

    Autosomal recessive retinitis pigmentosa (arRP) is a severe retinal dystrophy characterized by night blindness, progressive constriction of the visual fields and loss of central vision in the fourth or fifth decades. The frequency of this form of retinitis pigmentosa (RP) varies in different populations. Mutations within the rhodopsin, cyclic GMP phosphodiesterase-{beta} subunit and cGMP-gated channel genes have been reported in some arRP families. The genetic loci responsible for the majority of cases have yet to be identified. Genetic heterogeneity is likely to be extensive. In order to minimize the amount of genetic heterogenity, a set of arRP families was ascertained within the South-Central Sardinian population, in which 81% of families with a known mode of inheritance show an autosomal recessive form of RP. The Sardinian population is an ethnic {open_quotes}outlier{close_quotes}, having remained relatively isolated from mainland and other cultures. Genetic linkage data has been obtained in a set of 11 Sardinian arRP kindreds containing 26 affected members. Under the assumption of genetic homogeneity, no evidence of linkage was found in the arRP kindreds using 195 markers, which excluded 62% of the genome (Z<-2). Positive lod scores were obtained with D14S80 which showed no recombination in a subset of 5 families. Heterogeneity testing using D14S80 and arRP showed no significant evidence of heterogeneity (p=0.18) but evidence of linkage ({chi}{sup 2}=3.64, p=0.028). We are currently screening the neural retina-specific leucine zipper gene (NRL) in 14q11 for mutations as a candidate locus.

  4. Gastrocnemius recession as an alternative to tendoAchillis lengthening for relief of forefoot pressure in a patient with peripheral neuropathy: a case report and description of a technical modification.

    PubMed

    Greenhagen, Robert M; Johnson, Adam R; Peterson, Matthew C; Rogers, Lee C; Bevilacqua, Nicholas J

    2010-01-01

    The gastrocnemius recession is a popular surgical procedure for the treatment of equinus contracture. Lengthening the gastrocnemius tendon has been show to be an effective means of reducing pressure to the plantar forefoot by weakening the triceps surae complex. The more traditional method of weakening the triceps surae is a modification of Hoke's triple hemisection through the tendoAchillis. This technique unfortunately carries a serious risk of the development of a calcaneal gait. The purpose of this case report is to demonstrate that the gastrocnemius recession is an effective and safe alternative to the traditional tendoAchillis lengthening. The authors also describe a minimally invasive technique that uses a pediatric speculum for a self-retrained retractor and portal for instrumentation and visualization.

  5. Glacier recession in Iceland and Austria

    NASA Technical Reports Server (NTRS)

    Hall, Dorothy K.; Williams, Richard S., Jr.; Bayr, Klaus J.

    1992-01-01

    It has been possible to measure glacier recession on the basis of Landsat data, in conjunction with comparisons of the magnitude of recession of a glacier margin with in situ measurements at fixed points along the same margin. Attention is presently given to the cases of Vatnajokull ice cap, in Iceland, and the Pasterze Glacier, in Austria, on the basis of satellite data from 1973-1987 and 1984-1990, respectively. Indications of a trend toward negative mass balance are noted. Nevertheless, while most of the world's small glaciers have been receding, some are advancing either due to local climate or the tidewater glacier cycle.

  6. Glacier recession in Iceland and Austria

    SciTech Connect

    Hall, D.K.; Williams, R.S. Jr.; Bayr, K.J. USGS, Reston, VA Keene State College, NH )

    1992-03-01

    It has been possible to measure glacier recession on the basis of Landsat data, in conjunction with comparisons of the magnitude of recession of a glacier margin with in situ measurements at fixed points along the same margin. Attention is presently given to the cases of Vatnajokull ice cap, in Iceland, and the Pasterze Glacier, in Austria, on the basis of satellite data from 1973-1987 and 1984-1990, respectively. Indications of a trend toward negative mass balance are noted. Nevertheless, while most of the world's small glaciers have been receding, some are advancing either due to local climate or the tidewater glacier cycle. 21 refs.

  7. Nevada, the Great Recession, and Education

    ERIC Educational Resources Information Center

    Verstegen, Deborah A.

    2013-01-01

    The impact of the Great Recession and its aftermath has been devastating in Nevada, especially for public education. This article discusses the budget shortfalls and the impact of the economic crisis in Nevada using case study methodology. It provides a review of documents, including Governor Gibbon's proposals for the public K-12 education system…

  8. Reclaiming Recess: Learning the Language of Persuasion

    ERIC Educational Resources Information Center

    Gebhard, Meg; Harman, Ruth; Seger, Wendy

    2007-01-01

    Using a case study approach, the authors describe how a teacher used the tools of systemic functional linguistics (SFL) to teach her fifth grade English Language Learners how to use academic language to challenge school policies regarding recess. In reflecting on these data, we discuss the potential of SFL to support teachers in responding to…

  9. Nevada, the Great Recession, and Education

    ERIC Educational Resources Information Center

    Verstegen, Deborah A.

    2013-01-01

    The impact of the Great Recession and its aftermath has been devastating in Nevada, especially for public education. This article discusses the budget shortfalls and the impact of the economic crisis in Nevada using case study methodology. It provides a review of documents, including Governor Gibbon's proposals for the public K-12 education system…

  10. Epigenetic inheritance: Uncontested?

    PubMed Central

    Zhu, Bing; Reinberg, Danny

    2011-01-01

    “Epigenetics” is currently defined as “the inheritance of variation (-genetics) above and beyond (epi-) changes in the DNA sequence”. Despite the fact that histones are believed to carry important epigenetic information, little is known about the molecular mechanisms of the inheritance of histone-based epigenetic information, including histone modifications and histone variants. Here we review recent progress and discuss potential models for the mitotic inheritance of histone modifications-based epigenetic information. PMID:21321606

  11. Like Father, Like Daughter-inherited cutis aplasia occurring in a family with Marfan syndrome: a case report.

    PubMed

    Islam, Yasmin Florence Khodeja; Williams, Charles A; Schoch, Jennifer Jane; Andrews, Israel David

    2017-01-01

    We present the case of a newborn with co-occurrence of Marfan syndrome and aplasia cutis congenita (ACC) and a family history significant for Marfan syndrome and ACC in the father. This case details a previously unreported mutation in Marfan syndrome and describes a novel coinheritance of Marfan syndrome and ACC.

  12. A Case of Peeling Skin Syndrome.

    PubMed

    Singhal, Anil K; Yadav, Devendra K; Soni, Bajrang; Arya, Savita

    2017-01-01

    Peeling skin syndrome is a very rare autosomal recessive disease characterized by widespread painless peeling of the skin in superficial sheets. Etiology is still unknown with an autosomal recessive inheritance. Less than 100 cases have been reported in the medical literature. We present a 32-year-old man having asymptomatic peeling of skin since birth. Sheets of skin were peeling from his neck, trunk, and extremities, following friction or rubbing especially if pre-soaked in water but sparing palm and soles. Histologically, there was epidermal separation at the level of stratum corneum, just above the stratum granulosum. This case is being presented due to its rarity.

  13. Process Centerless Recess Grinding

    NASA Astrophysics Data System (ADS)

    Malík, Andrej; Görög, Augustín

    2010-01-01

    The article deals with special centerless grinding using various methods, particularly the centerless grinding recess methods. The results of measuring the surface roughness of frontal and cylindrical areas of a workpiece, as well as the roundness of the cylindrical surface of the workpiece are presented in the paper. Qualitative parameters of the machined surfaces are supplemented by the course of the grinding process. The change in the shape of the workpiece in the process of grinding causes also the change of position of the workpiece in the work zone.

  14. Dominant and Recessive Forms of Fibrochondrogenesis Resulting from Mutations at a Second Locus, COL11A2

    PubMed Central

    Tompson, Stuart W.; Faqeih, Eissa Ali; Ala-Kokko, Leena; Hecht, Jacqueline T.; Miki, Rika; Funari, Tara; Funari, Vincent A.; Nevarez, Lisette; Krakow, Deborah; Cohn, Daniel H.

    2011-01-01

    Fibrochondrogenesis is a severe, recessively inherited skeletal dysplasia shown to result from mutations in the gene encoding the proα1(XI) chain of type XI collagen, COL11A1. The first of two cases reported here was the affected offspring of first cousins and sequence analysis excluded mutations in COL11A1. Consequently, whole-genome SNP genotyping was performed to identify blocks of homozygosity, identical-by-descent, wherein the disease locus would reside. COL11A1 was not within a region of homozygosity, further excluding it as the disease locus, but the gene encoding the proα2(XI) chain of type XI collagen, COL11A2, was located within a large region of homozygosity. Sequence analysis identified homozygosity for a splice donor mutation in intron 18. Exon trapping demonstrated that the mutation resulted in skipping of exon 18 and predicted deletion of 18 amino acids from the triple helical domain of the protein. In the second case, heterozygosity for a de novo 9 bp deletion in exon 40 of COL11A2 was identified, indicating that there are autosomal dominant forms of fibrochondrogenesis. These findings thus demonstrate that fibrochondrogenesis can result from either recessively- or dominantly-inherited mutations in COL11A2. PMID:22246659

  15. 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.

  16. Reduced Toxicity Conditioning and Allogeneic Hematopoietic Progenitor Cell Transplantation for Recessive Dystrophic Epidermolysis Bullosa.

    PubMed

    Geyer, Mark B; Radhakrishnan, Kavita; Giller, Roger; Umegaki, Noriko; Harel, Sivan; Kiuru, Maija; Morel, Kimberly D; LeBoeuf, Nicole; Kandel, Jessica; Bruckner, Anna; Fabricatore, Sandra; Chen, Mei; Woodley, David; McGrath, John; Baxter-Lowe, LeeAnn; Uitto, Jouni; Christiano, Angela M; Cairo, Mitchell S

    2015-09-01

    Recessive dystrophic epidermolysis bullosa is a severe, incurable, inherited blistering disease caused by COL7A1 mutations. Emerging evidence suggests hematopoietic progenitor cells (HPCs) can be reprogrammed into skin; HPC-derived cells can restore COL7 expression in COL7-deficient mice. We report two children with recessive dystrophic epidermolysis bullosa treated with reduced-toxicity conditioning and HLA-matched HPC transplantation.

  17. Inheritance of apospory in bahiagrass, Paspalum notatum.

    PubMed

    Martínez, E J; Urbani, M H; Quarin, C L; Ortiz, J P

    2001-01-01

    Previous studies on the inheritance of aposporous apomixis in bahiagrass showed a wide range of segregation ratios in crosses involving sexual and aposporous apomictic plants. The F1 progenies were classified through a visual progeny test carried out on few F2 plants. The number of sexual F1s highly exceeded the apomictics leading to the conclusion that apomixis was controlled by a few recessive genes. The present study examines the inheritance of apospory in bahiagrass. A sexual plant was self-pollinated and crossed with an aposporous apomictic plant as pollen donor. Backcross and F2 progenies were obtained in several combinations. All self-pollinated sexual plants or sexual x sexual crosses produced progenies free of apospory. All crosses involving a sexual and an apomictic plant produced approximately three times more apospory-free plants than plants with apospory. Bahiagrass is of autotetraploid origin and hence is expected to display tetrasomic inheritance. The most widely accepted genetic model for inheritance of apospory in tropical grasses is a single dominant gene with tetrasomic inheritance. In the present experiments none of the apospory-free F1s segregated for the apospory trait indicating that it is most likely a dominant character. However, the observed results fit better a modified model: tetrasomic inheritance of a single dominant gene with pleiotropic effect and incomplete penetrance. The excess of apospory-free plants in the F1 progeny could be ascribed to some distortion in the segregation pattern due to a pleiotropic lethal effect of the dominant A allele with incomplete penetrance. Alternatively, partial lethality of factors linked to aposporous gene may account for segregation distortion against apospory.

  18. Mutations in the HSP27 (HSPB1) gene cause dominant, recessive, and sporadic distal HMN/CMT type 2.

    PubMed

    Houlden, H; Laura, M; Wavrant-De Vrièze, F; Blake, J; Wood, N; Reilly, M M

    2008-11-18

    Charcot-Marie-Tooth disease (CMT) is the most common inherited neuromuscular disorder and is characterized by significant clinical and genetic heterogeneity. Recently, mutations in both the small heat shock protein 27 (HSP27 or HSPB1) and 22 (HSP22 or HSPB8) genes have been reported to cause autosomal dominant CMT with minimal sensory involvement (CMT 2F/CMT2L) and autosomal dominant distal hereditary motor neuropathy type II (dHMN II). We analyzed the HSPB1 and HSPB8 genes in a large clinically well-characterized series of dHMN and CMT type 2 (CMT2) cases and families using linkage analysis and direct sequencing of these genes. We identified a novel homozygous mutation in the alpha-crystallin domain of HSPB1 segregating in an autosomal recessive fashion in a family with distal HMN/CMT2. A further four heterozygous HSPB1 mutations were identified in four autosomal dominant families dHMN/CMT2, and two sporadic cases were identified with probable de novo mutations. In the autosomal dominant and autosomal recessive families, there were no clinical sensory findings, but reduced sural nerve action potential amplitudes were found in some affected individuals, indicating that long sensory axons are mildly affected in this predominantly motor disorder. This extends the clinical and electrophysiologic spectrum of HSPB1 mutations and identifies four unreported dominant HSPB1 mutations and the first family where the HSPB1 mutation acts in a recessive way to cause distal HMN.

  19. Inherited resistance to Corynebacterium kutscheri in mice.

    PubMed Central

    Hirst, R G; Wallace, M E

    1976-01-01

    An analysis of the factors responsible for inherited resistance to Corynebacterium kutscheri was undertaken. Various inbred mouse strains were examined; these included the Swiss Lynch and C57Bl/l mice, their F1 and F2 progeny, and the progeny of the F1 backcrossed to each parent strain. Two modes of inherited resistance are described. An examination suggested that resistance as measured by the mean lethal dose of C. kutscheri was under polygenic control and was inherited continuously. However, the efficiency with which C. kutscheri was eliminated by the mononuclear phagocyte cells of the liver over 3 days differed markedly among strains. A genetic analysis of this mononuclear phagocyte microbicidal efficiency (MPME) in Swiss Lynch and C57Bl/6 mice was undertaken. The trait, MPME, was present, but did not segregate, in the F1 progeny or in the progeny of the backcross to the resistant C57Bl/6 parent; this was clear evidence of dominance. Moreover, MPME segregated in a ratio of 1:1 in the progeny of the backcross to the sensitive Swiss Lynch parent and in a ratio of 3:1 in the F2 progeny. It was concluded that MPME was inherited discontinuously and was controlled by a single dominant autosomal gene (or closely linked group); the recessive allele was assigned the gene symbol ack. Linkage experiments showed there to be no association between the ack locus and any of the immune-response genes. PMID:971958

  20. CT of the pericardial recesses

    SciTech Connect

    Levy-Ravetch, M.; Auh, Y.H.; Rubenstein, W.A.; Whalen, J.P.; Kazam, E.

    1985-04-01

    Within the pericardial cavity there are several recesses where fluid can collect in close contiguity to the major bronchi and lymph nodes. These include the transverse sinus, behind the ascending aorta and pulmonary trunk; the oblique sinus, behind the left atrium; and the left pulmonic recess, between the left pulmonary artery and the left superior pulmonary vein. There are also smaller pericardial recesses between the superior and inferior pulmonary veins, posterolateral to the superior vena cava, and between the inferior vena cava and coronary sinus. An understanding of sectional anatomy is valuable for differentiation of fluid within these recesses from mediastinal masses or enlarged lymph nodes on computed tomographic scans.

  1. Lamellar Icthyosis – A case Report

    PubMed Central

    B.V, Thimma Reddy; V, Daneswari; Deshmukh, Sudhanwan N

    2014-01-01

    Autosomal recessive congenital ichthyosis is a heterogenous group of disorders that are present at birth with generalized involvement of skin and lack of other organ systems. Clinical presentation, pattern of inheritance, and laboratory evaluation may establish a precise diagnosis, which can assist in prognosis and genetic counseling. There is a little knowledge about the oral manifestations of these disorders.This case report presents management and complete oral rehabilitation of a rare case of lamellar ichthyosis. PMID:25584329

  2. Inherited Thrombocytopenia with a Different Type of Gene Mutation: A Brief Literature Review and Two Case Studies

    PubMed Central

    Arzanian, Mohammad Taghi

    2016-01-01

    Hereditary thrombocytopenias are rare bleeding disorders, which cause a deficiency of platelets in early infancy. This group of disorders is sometimes associated with abnormal phenotypes, like absence of radius. Diagnosis of this type of thrombocytopenia is usually difficult; other causes of thrombocytopenia, such as immune disorders and infections, must be ruled out. The symptoms of hereditary thrombocytopenia also vary from seldom and mild to severe bleeding and occasionally may first occur in late childhood. In this group of patients, we must differentiate heritable disorders from the acquired types of thrombocytopenia, like immune thrombocytopenic purpura. It is also important to watch for pitfalls to avoid unnecessary and potentially hazardous treatment. Herein, we briefly review the recent literature on hereditary thrombocytopenia and then present the cases of two referred patients. The first case had suffered from persistent thrombocytopenia since early infancy and was diagnosed with congenital amegakaryocytic thrombocytopenia, while the other patient presented with Wiskott - Aldrich syndrome. PMID:28203325

  3. Primary Autosomal Recessive Microcephaly: MCPH5 Maps to 1q25-q32

    PubMed Central

    Jamieson, C. Ruth; Fryns, Jean-Pierre; Jacobs, Jos; Matthijs, Gert; Abramowicz, Marc J.

    2000-01-01

    Primary microcephaly is thought to result from genetic defects of the developmental program that generates large brain hemispheres in humans. Autosomal recessive inheritance is likely in most familial cases, and four loci were recently mapped by homozygosity. We report homozygosity mapping of a new locus, MCPH5, with a maximum multipoint LOD score of 3.51 at marker D1S1723, in a family of Turkish origin. The minimal critical region spans 11.4 cM between markers D1S384 and D1S2655, at 1q25-q32, and encompasses the cytogenetic breakpoints of chromosomal aberrations previously reported in unrelated patients with microcephaly. PMID:11067780

  4. Clinical delineation of Giuffrè-Tsukahara syndrome: another case with microcephaly and radio-ulnar synostosis with apparent X-linked semi-dominant inheritance.

    PubMed

    Gaspar, Harald; Albermann, Kurt; Baumer, Alessandra; Schinzel, Albert

    2008-06-01

    Two families and three sporadic cases have been described so far with the combination of radio-ulnar synostosis and microcephaly as main features. Some authors have discussed whether the first family reported by Giuffrè et al. [1994] and the second family described by Tsukahara et al. [1995] had the same syndrome. Although there is phenotypic variability among the described cases (especially with respect to facial dysmorphisms and mental retardation), the clinical patterns do not seem to be clearly distinguishable from each other. We describe another family with apparent X-linked semi-dominant inheritance with milder features in the female patient due to skewed X-inactivation. From a clinical synopsis, we consider the Giuffrè-Tsukahara syndrome as one genetic entity, which is characterized by the association of microcephaly and radio-ulnar synostosis, mental retardation in male patients and variable minor features. Patients with the Giuffrè-Tsukahara syndrome do not present with a characteristic pattern of facial features.

  5. Founder mutations in NDRG1 and HK1 genes are common causes of inherited neuropathies among Roma/Gypsies in Slovakia.

    PubMed

    Gabrikova, Dana; Mistrik, Martin; Bernasovska, Jarmila; Bozikova, Alexandra; Behulova, Regina; Tothova, Iveta; Macekova, Sona

    2013-11-01

    Autosomal recessive forms of Charcot-Marie-Tooth disease (CMT) account for less than 10 % of all CMT cases, but are more frequent in the populations with a high rate of consanguinity. Roma (Gypsies) are a transnational minority with an estimated population of 10 to 14 million, in which a high degree of consanguineous marriages is a generally known fact. Similar to the other genetically isolated founder populations, the Roma harbour a number of unique or rare autosomal recessive disorders, caused by "private" founder mutations. There are three subtypes of autosomal recessive CMT with mutations private to the Roma population: CMT4C, CMT4D and CMT4G. We report on the molecular examination of four families of Roma origin in Slovakia with early-onset demyelinating neuropathy and autosomal recessive inheritance. We detected mutation p.R148X (g.631C>T) in the NDRG1 (NM_006096.3) gene in two families and mutation g.9712G>C in the HK1 (NM_033498) gene in the other two families. These mutations cause CMT4D and CMT4G, respectively. The success of molecular genetic analysis in all families confirms that autosomal recessive forms of CMT caused by mutations on the NDRG1 and HK1 genes are common causes of inherited neuropathies among Slovak Roma. Providing genetic analysis of these genes for patients with Roma origin as a common part of diagnostic procedure would contribute to a better rate of diagnosed cases of demyelinating neuropathy in Slovakia and in other countries with a Roma minority.

  6. 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

  7. Analysis of the inheritance pattern of a Chinese family with phaeochromocytomas through whole exome sequencing.

    PubMed

    Cao, Min; Sun, Fukang; Huang, Xin; Dai, Jun; Cui, Bin; Ning, Guang

    2013-09-10

    Phaeochromocytomas (PCCs) and paragangliomas (PGLs) are rare, catecholamine-producing tumors. Most familial PCC/PGLs have been detected to be autosomal dominantly inherited. However, this study was undertaken in a family with PCCs to determine candidate genes in a dominant or recessive inheritance pattern. After excluding mutations in ten PCC/PGL susceptibility genes by Sanger sequencing, we used whole exome sequencing for screening on the four family members to discover novel candidate genes associated with PCCs. Based on the inexistence of non-synonymous mutations or indels in the ten known genes and the structure of this pedigree, 3 damaging loci with dominant inheritance pattern, and 5 damaging loci with recessive homozygous inheritance pattern and 6 damaging genes with compound heterozygous inheritance pattern were narrowed down to indicate the association with PCCs. According to the Gene Ontology (GO) category analysis on the combined results, cell adhesion showed the most significant enrichment.

  8. Discriminative Features in Three Autosomal Recessive Cutis Laxa Syndromes: Cutis Laxa IIA, Cutis Laxa IIB, and Geroderma Osteoplastica

    PubMed Central

    Kariminejad, Ariana; Afroozan, Fariba; Bozorgmehr, Bita; Ghanadan, Alireza; Akbaroghli, Susan; Khorram Khorshid, Hamid Reza; Mojahedi, Faezeh; Setoodeh, Aria; Loh, Abigail; Tan, Yu Xuan; Escande-Beillard, Nathalie; Malfait, Fransiska; Reversade, Bruno; Gardeitchik, Thatjana; Morava, Eva

    2017-01-01

    Cutis laxa is a heterogeneous condition characterized by redundant, sagging, inelastic, and wrinkled skin. The inherited forms of this disease are rare and can have autosomal dominant, autosomal recessive, or X-linked inheritance. Three of the autosomal recessive cutis laxa syndromes, namely cutis laxa IIA (ARCL2A), cutis laxa IIB (ARCL2B), and geroderma osteodysplastica (GO), have very similar clinical features, complicating accurate diagnosis. Individuals with these conditions often present with cutis laxa, progeroid features, and hyperextensible joints. These conditions also share additional features, such as short stature, hypotonia, and congenital hip dislocation, but the severity and frequency of these findings are variable in each of these cutis laxa syndromes. The characteristic features for ARCL2A are abnormal isoelectric focusing and facial features, including downslanting palpebral fissures and a long philtrum. Rather, the clinical phenotype of ARCL2B includes severe wrinkling of the dorsum of the hands and feet, wormian bones, athetoid movements, lipodystrophy, cataract and corneal clouding, a thin triangular face, and a pinched nose. Normal cognition and osteopenia leading to pathological fractures, maxillary hypoplasia, and oblique furrowing from the outer canthus to the lateral border of the supraorbital ridge are discriminative features for GO. Here we present 10 Iranian patients who were initially diagnosed clinically using the respective features of each cutis laxa syndrome. Each patient’s clinical diagnosis was then confirmed with molecular investigation of the responsible gene. Review of the clinical features from the cases reported from the literature also supports our conclusions. PMID:28294978

  9. Impact of transgene inheritance on the mitigation of gene flow between crops and their wild relatives: the example of foxtail millet.

    PubMed

    Shi, Yunsu; Wang, Tianyu; Li, Yu; Darmency, Henri

    2008-10-01

    Developing genetically modified crop plants that are biologically contained could reduce significantly the potential spread of transgenes to conventional and organic crop plants and to wild or weedy relatives. Among several strategies, the hereditary mode of transmission of transgenes, whether dominant, recessive, or maternal, could play a major role in interspecific gene flow. Here we report on the gene flow between foxtail millet (Setaria italica), an autogamous crop, and its weedy relative, S. viridis, growing within or beside fields containing the three kinds of inherited herbicide resistance. Over the 6-year study, in the absence of herbicide selection, the maternal chloroplast-inherited resistance was observed at a 2 x 10(-6) frequency in the weed populations. Resistant weed plants were observed 60 times as often, at 1.2 x 10(-4) in the case of the nuclear recessive resistance, and 190 times as often, at 3.9 x 10(-4) in the case of the dominant resistance. Because the recessive gene was not expressed in the first-generation hybrids, it should be more effective than dominant genes in reducing gene flow under normal agricultural conditions where herbicides are sprayed because interspecific hybrids cannot gain from beneficial genes.

  10. Autosomal recessive hyper IgM syndrome associated with activation-induced cytidine deaminase gene in three Turkish siblings presented with tuberculosis lymphadenitis - Case report.

    PubMed

    Patiroglu, Turkan; Akar, H Haluk; van der Burg, Mirjam; Unal, Ekrem

    2015-09-01

    The hyper-immunoglobulin M (HIGM) syndrome is a heterogeneous group of genetic disorders characterized by recurrent infections, decreased serum levels of immunoglobulin G (IgG) and IgA, and normal/increased serum levels of IgM. Herein, we describe three Turkish siblings with HIGM syndrome who had a homozygous missense mutation (c.70C>T, p.Arg24Trp) in the activation-induced cytidine deaminase gene which results in autosomal recessive HIGM syndrome. Two of the siblings, sibling 1 and sibling 3, presented with cervical deep abscess and cervical tuberculosis lymphadenitis, respectively.

  11. Endoscopic Gastrocnemius Intramuscular Aponeurotic Recession

    PubMed Central

    Lui, Tun Hing

    2015-01-01

    Gastrocnemius aponeurotic recession is the surgical treatment for symptomatic gastrocnemius contracture. Endoscopic gastrocnemius recession procedures has been developed recently and reported to have fewer complications and better cosmetic outcomes. Classically, this is performed at the aponeurosis distal to the gastrocnemius muscle attachment. We describe an alternative endoscopic approach in which the intramuscular portion of the aponeurosis is released. PMID:26900563

  12. Fort Play Children Recreate Recess

    ERIC Educational Resources Information Center

    Powell, Mark

    2007-01-01

    Recess beckons well before it actually arrives. Its allure can be heard in children's lunchtime conversations as they discuss imaginary roles, plans, alliances and teams, with an obvious appetite for play and its unbounded possibility. For some children, recess provides the most important reasons to come to school. In team sports, games of chase…

  13. Fort Play Children Recreate Recess

    ERIC Educational Resources Information Center

    Powell, Mark

    2007-01-01

    Recess beckons well before it actually arrives. Its allure can be heard in children's lunchtime conversations as they discuss imaginary roles, plans, alliances and teams, with an obvious appetite for play and its unbounded possibility. For some children, recess provides the most important reasons to come to school. In team sports, games of chase…

  14. Endoscopic Gastrocnemius Intramuscular Aponeurotic Recession.

    PubMed

    Lui, Tun Hing

    2015-10-01

    Gastrocnemius aponeurotic recession is the surgical treatment for symptomatic gastrocnemius contracture. Endoscopic gastrocnemius recession procedures has been developed recently and reported to have fewer complications and better cosmetic outcomes. Classically, this is performed at the aponeurosis distal to the gastrocnemius muscle attachment. We describe an alternative endoscopic approach in which the intramuscular portion of the aponeurosis is released.

  15. Comprehensive Carrier Screening and Molecular Diagnostic Testing for Recessive Childhood Diseases

    PubMed Central

    Kingsmore, Stephen

    2012-01-01

    Of 7,028 disorders with suspected Mendelian inheritance, 1,139 are recessive and have an established molecular basis. Although individually uncommon, Mendelian diseases collectively account for ~20% of infant mortality and ~18% of pediatric hospitalizations. Molecular diagnostic testing is currently available for only ~300 recessive disorders. Preconception screening, together with genetic counseling of carriers, has resulted in remarkable declines in the incidence of several severe recessive diseases including Tay-Sachs disease and cystic fibrosis. However, extension of preconception screening and molecular diagnostic testing to most recessive disease genes has hitherto been impractical. Recently, we reported a preconception carrier screen / molecular diagnostic test for 448 recessive childhood diseases. The current status of this test is reviewed here. Currently, this reports analytical validity of the comprehensive carrier test. As the clinical validity and clinical utility in the contexts described is ascertained, this article will be updated. PMID:22872815

  16. Inherited epidermolysis bullosa

    PubMed Central

    2010-01-01

    Inherited epidermolysis bullosa (EB) encompasses a number of disorders characterized by recurrent blister formation as the result of structural fragility within the skin and selected other tissues. All types and subtypes of EB are rare; the overall incidence and prevalence of the disease within the United States is approximately 19 per one million live births and 8 per one million population, respectively. Clinical manifestations range widely, from localized blistering of the hands and feet to generalized blistering of the skin and oral cavity, and injury to many internal organs. Each EB subtype is known to arise from mutations within the genes encoding for several different proteins, each of which is intimately involved in the maintenance of keratinocyte structural stability or adhesion of the keratinocyte to the underlying dermis. EB is best diagnosed and subclassified by the collective findings obtained via detailed personal and family history, in concert with the results of immunofluorescence antigenic mapping, transmission electron microscopy, and in some cases, by DNA analysis. Optimal patient management requires a multidisciplinary approach, and revolves around the protection of susceptible tissues against trauma, use of sophisticated wound care dressings, aggressive nutritional support, and early medical or surgical interventions to correct whenever possible the extracutaneous complications. Prognosis varies considerably and is based on both EB subtype and the overall health of the patient. PMID:20507631

  17. Inherited mitochondrial neuropathies.

    PubMed

    Finsterer, Josef

    2011-05-15

    Mitochondrial disorders (MIDs) occasionally manifest as polyneuropathy either as the dominant feature or as one of many other manifestations (inherited mitochondrial neuropathy). MIDs in which polyneuropathy is the dominant feature, include NARP syndrome due to the transition m.8993T>, CMT2A due to MFN2 mutations, CMT2K and CMT4A due to GDAP1 mutations, and axonal/demyelinating neuropathy with external ophthalmoplegia due to POLG1 mutations. MIDs in which polyneuropathy is an inconstant feature among others is the MELAS syndrome, MERRF syndrome, LHON, Mendelian PEO, KSS, Leigh syndrome, MNGIE, SANDO; MIRAS, MEMSA, AHS, MDS (hepato-cerebral form), IOSCA, and ADOA syndrome. In the majority of the cases polyneuropathy presents in a multiplex neuropathy distribution. Nerve conduction studies may reveal either axonal or demyelinated or mixed types of neuropathies. If a hereditary neuropathy is due to mitochondrial dysfunction, the management of these patients is at variance from non-mitochondrial hereditary neuropathies. Patients with mitochondrial hereditary neuropathy need to be carefully investigated for clinical or subclinical involvement of other organs or systems. Supportive treatment with co-factors, antioxidants, alternative energy sources, or lactate lowering agents can be tried. Involvement of other organs may require specific treatment. Mitochondrial neuropathies should be included in the differential diagnosis of hereditary neuropathies. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. Recessive resistance genes and the Oryza sativa-Xanthomonas oryzae pv. oryzae pathosystem.

    PubMed

    Iyer-Pascuzzi, Anjali S; McCouch, Susan R

    2007-07-01

    Though recessive resistance is well-studied in viral systems, little is understood regarding the phenomenon in plant-bacterial interactions. The Oryza sativa-Xanthomonas oryzae pv. orzyae pathosystem provides an excellent opportunity to examine recessive resistance in plant-bacterial interactions, in which nine of 30 documented resistance (R) genes are recessively inherited. Infestations of X. oryzae pv. oryzae, the causal agent of bacterial blight, result in significant crop loss and damage throughout South and Southeast Asia. Two recently cloned novel recessive R genes, xa5 and xa13, have yielded insights to this system. Like their viral counterparts, these bacterial recessive R gene products do not conform to the five commonly described classes of R proteins. New findings suggest that such genes may more aptly be viewed as mutations in dominant susceptibility alleles and may also function in a gene-for-gene manner. In this review, we discuss recent accomplishments in the understanding of recessively inherited R genes in the rice-bacterial blight pathosystem and suggest a new model for the function of recessive resistance in plant-bacterial interactions.

  19. Children's Understanding of Inheritance.

    ERIC Educational Resources Information Center

    Clough, Elizabeth Engel; Wood-Robinson, Colin

    1985-01-01

    Investigated common belief patterns secondary school students (N=84) have about inheritance, noting the most prevalent misconceptions about genetics which occur at different age levels. Implications based on findings and suggestions for teaching lower secondary courses are included. (ML)

  20. Inheritance in tetraploid yeast revisited: segregation patterns and statistical power under different inheritance models.

    PubMed

    Stift, M; Reeve, R; van Tienderen, P H

    2010-07-01

    In their recent article, Albertin et al. (2009) suggest an autotetraploid origin of 10 tetraploid strains of baker's yeast (Saccharomyces cerevisiae), supported by the frequent observation of double reduction meiospores. However, the presented inheritance results were puzzling and seemed to contradict the authors' interpretation that segregation ratios support a tetrasomic model of inheritance. Here, we provide an overview of the expected segregation ratios at the tetrad and meiospore level given scenarios of strict disomic and tetrasomic inheritance, for cases with and without recombination between locus and centromere. We also use a power analysis to derive adequate sample sizes to distinguish alternative models. Closer inspection of the Albertin et al. data reveals that strict disomy can be rejected in most cases. However, disomic inheritance with strong but imperfect preferential pairing could not be excluded with the sample sizes used. The possibility of tetrad analysis in tetraploid yeast offers a valuable opportunity to improve our understanding of meiosis and inheritance of tetraploids.

  1. Inheritance of gynoecism in bitter gourd (Momordica charantia L.).

    PubMed

    Ram, Dangar; Kumar, Sanjeet; Singh, Major; Rai, Mathura; Kalloo, Gautam

    2006-01-01

    The inheritance of sex expression in cucumber (Cucumis sativus) and other cucurbits is well documented; however, the genetics of female sex (gynoecism) expression in bitter gourd (Momordica charantia) has not been described. Inheritance of gynoecism in bitter gourd was studied in a 100% gynoecious line (Gy263B). The F(2) and testcross segregation data revealed that gynoecism in Gy263B is under the control of a single, recessive gene. Following the gene nomenclature of cucurbits, it is proposed that the gene symbol, gy-1, be assigned for the expression of gynoecism in bitter gourd.

  2. Autosomal recessive causes likely in early-onset Alzheimer disease.

    PubMed

    Wingo, Thomas S; Lah, James J; Levey, Allan I; Cutler, David J

    2012-01-01

    To determine the genetic contribution to non-autosomal dominant early-onset Alzheimer disease (EOAD) (onset age ≤60 years) cases and identify the likely mechanism of inheritance in those cases. A liability threshold model of disease was used to estimate heritability of EOAD and late-onset Alzheimer disease (AD) using concordance for AD among parent-offspring pairs. The Uniform Data Set, whose participants were collected from 32 US Alzheimer's Disease Centers, maintained by the National Alzheimer's Coordinating Center. Individuals with probable AD and detailed parental history (n = 5370). The concordance among relatives and heritability of EOAD and late-onset AD. For late-onset AD (n = 4302), we found sex-specific parent-offspring concordance that ranged from approximately 10% to 30%, resulting in a heritability of 69.8% (95% confidence interval, 64.6%-75.0%), and equal heritability for both sexes regardless of parental sex. For EOAD (n = 702), we found that the parent-offspring concordance was 10% or less and concordance among siblings was 21.6%. Early-onset AD heritability was 92% to 100% for all likely values of EOAD prevalence. We confirm late-onset AD is a highly polygenic disease. By contrast, the data for EOAD suggest it is an almost entirely genetically based disease, and the patterns of observed concordance for parent-offspring pairs and among siblings lead us to reject the hypotheses that EOAD is a purely dominant, mitochondrial, X-linked, or polygenic disorder. The most likely explanation of the data is that approximately 90% of EOAD cases are due to autosomal recessive causes.

  3. Patterns of mitochondrial inheritance in the myxogastrid Didymium iridis.

    PubMed

    Silliker, Margaret E; Liles, Jeffery L; Monroe, Jason A

    2002-01-01

    Seven strains of the Central American A1 mating series of Didymium iridis were crossed in all possible combinations. Individual plasmodia were isolated and grown to a stage where total DNA could be isolated for DNA-DNA hybridization with cloned mitochondrial DNA probes to determine the pattern of mitochondrial inheritance. Random, biased, and dominant patterns of uniparental mitochondrial inheritance were observed, as well as rare cases of biparental inheritance, depending on the particular parental strains mated. The diverse patterns suggest that the factors controlling mitochondrial inheritance in D. iridis are complex. Differences between trials of the same matings suggest that non-genetic factors may also influence mitochondrial inheritance.

  4. Autosomal recessive Alport syndrome: an in-depth clinical and molecular analysis of five families.

    PubMed

    Longo, Ilaria; Scala, Elisa; Mari, Francesca; Caselli, Rossella; Pescucci, Chiara; Mencarelli, Maria Antonietta; Speciale, Caterina; Giani, Marisa; Bresin, Elena; Caringella, Domenica Angela; Borochowitz, Zvi-Uri; Siriwardena, Komudi; Winship, Ingrid; Renieri, Alessandra; Meloni, Ilaria

    2006-03-01

    Alport syndrome (ATS) is a progressive inherited nephropathy characterized by irregular thinning, thickening and splitting of the glomerular basement membrane (GBM) often associated with hearing loss and ocular symptoms. ATS has been shown to be caused by COL4A5 mutations in its X-linked form and by COL4A3 and COL4A4 mutations in its autosomal forms. Five families with a suspicion of ATS were investigated both from a clinical and molecular point of view. COL4A3 and COL4A4 genes were analysed by DHPLC. Automated sequencing was performed to identify the underlying mutation. Molecular analysis indicated that in all 5 cases the correct diagnosis was autosomal recessive ATS. In three families in which parental consanguinity clearly pinpointed to autosomal recessive ATS, we found COL4A4 homozygous mutations in two of them and COL4A3 homozygous mutation in the other one. In the remaining two families a differential diagnosis including X-linked ATS, autosomal recessive ATS and thin basement membrane nephropathy was considered. The molecular analysis demonstrated that the probands were genetic compounds for two different mutations in the COL4A4 gene pinpointing to the correct diagnosis of autosomal recessive ATS. A clinical evaluation of probands and their relatives of the five families carrying mutations in either the COL4A3 or the COL4A4 gene was carried out to underline the natural history of the autosomal recessive ATS. In addition, this paper stresses the complexity of the clinics and genetics of ATS and how a correct diagnosis is based on a combination of: (i) an in-depth clinical investigation; (ii) a detailed formal genetic analysis; (iii) a correct technical choice of the gene to be investigated; (iv) a correct technical choice of the family member to be included in the mutational screening. A correct diagnosis is the basis for an appropriate genetic counselling dealing with both the correct prognosis and the accurate recurrence risk for the patients and family

  5. Inherited predisposition to multiple myeloma

    PubMed Central

    Koura, Divya T.

    2013-01-01

    Multiple myeloma (MM) is the second most common hematologic malignancy in the United States, after non-Hodgkin lymphoma. Family pedigree analyses of high-risk families, case-control studies and racial disparities in disease incidence all point to a potential inherited predisposition to MM. Genome-wide association studies (GWASs) have identified susceptibility loci in a number of cancers and such studies are currently underway in MM. To date, GWASs in MM have identified several potential regions of interest for further study on chromosomes 3p22, 7p15.3, 8q24 and 2p23.3. In addition, several targets of paraproteins (so called ‘paratargs’) in MM have been identified. Hyperphosphorylation of the paratarg protein, which is inherited in an autosomal dominant manner, appears a common mechanism underlying the antigenicity of these proteins. One particular protein, hyperphosphorylated paratarg-7 (pP-7) is a common target in persons with myeloma and has also been identified in affected members of several high-risk MM families. It appears that the frequency of pP-7 as an antigenic target may be particularly high in African American patients with MM, which could be part of the explanation for observed racial disparities in the incidence of MM. In this review we focus on available data in the area of inherited predisposition to MM, and highlight future research directions. PMID:23926460

  6. Phenotypic characterization of recessive gene knockout rat models of Parkinson's disease.

    PubMed

    Dave, Kuldip D; De Silva, Shehan; Sheth, Niketa P; Ramboz, Sylvie; Beck, Melissa J; Quang, Changyu; Switzer, Robert C; Ahmad, Syed O; Sunkin, Susan M; Walker, Dan; Cui, Xiaoxia; Fisher, Daniel A; McCoy, Aaron M; Gamber, Kevin; Ding, Xiaodong; Goldberg, Matthew S; Benkovic, Stanley A; Haupt, Meredith; Baptista, Marco A S; Fiske, Brian K; Sherer, Todd B; Frasier, Mark A

    2014-10-01

    Recessively inherited loss-of-function mutations in the PTEN-induced putative kinase 1(Pink1), DJ-1 (Park7) and Parkin (Park2) genes are linked to familial cases of early-onset Parkinson's disease (PD). As part of its strategy to provide more tools for the research community, The Michael J. Fox Foundation for Parkinson's Research (MJFF) funded the generation of novel rat models with targeted disruption ofPink1, DJ-1 or Parkin genes and determined if the loss of these proteins would result in a progressive PD-like phenotype. Pathological, neurochemical and behavioral outcome measures were collected at 4, 6 and 8months of age in homozygous KO rats and compared to wild-type (WT) rats. Both Pink1 and DJ-1 KO rats showed progressive nigral neurodegeneration with about 50% dopaminergic cell loss observed at 8 months of age. ThePink1 KO and DJ-1 KO rats also showed a two to three fold increase in striatal dopamine and serotonin content at 8 months of age. Both Pink1 KO and DJ-1 KO rats exhibited significant motor deficits starting at 4months of age. However, Parkin KO rats displayed normal behaviors with no neurochemical or pathological changes. These results demonstrate that inactivation of the Pink1 or DJ-1 genes in the rat produces progressive neurodegeneration and early behavioral deficits, suggesting that these recessive genes may be essential for the survival of dopaminergic neurons in the substantia nigra (SN). These MJFF-generated novel rat models will assist the research community to elucidate the mechanisms by which these recessive genes produce PD pathology and potentially aid in therapeutic development.

  7. Pathognomonic oral profile of Enamel Renal Syndrome (ERS) caused by recessive FAM20A mutations

    PubMed Central

    2014-01-01

    Amelogenesis imperfecta (AI) is a genetically and clinically heterogeneous group of inherited dental enamel defects. Commonly described as an isolated trait, it may be observed concomitantly with other orodental and/or systemic features such as nephrocalcinosis in Enamel Renal Syndrome (ERS, MIM#204690), or gingival hyperplasia in Amelogenesis Imperfecta and Gingival Fibromatosis Syndrome (AIGFS, MIM#614253). Patients affected by ERS/AIGFS present a distinctive orodental phenotype consisting of generalized hypoplastic AI affecting both the primary and permanent dentition, delayed tooth eruption, pulp stones, hyperplastic dental follicles, and gingival hyperplasia with variable severity and calcified nodules. Renal exam reveals a nephrocalcinosis which is asymptomatic in children affected by ERS. FAM20A recessive mutations are responsible for both syndromes. We suggest that AIGFS and ERS are in fact descriptions of the same syndrome, but that the kidney phenotype has not always been investigated fully in AIGFS. The aim of this review is to highlight the distinctive and specific orodental features of patients with recessive mutations in FAM20A. We propose ERS to be the preferred term for all the phenotypes arising from recessive FAM20A mutations. A differential diagnosis has to be made with other forms of AI, isolated or syndromic, where only a subset of the clinical signs may be shared. When ERS is suspected, the patient should be assessed by a dentist, nephrologist and clinical geneticist. Confirmed cases require long-term follow-up. Management of the orodental aspects can be extremely challenging and requires the input of multi-disciplinary specialized dental team, especially when there are multiple unerupted teeth. PMID:24927635

  8. Autosomal recessive nonsyndromic deafness genes: a review.

    PubMed

    Duman, Duygu; Tekin, Mustafa

    2012-06-01

    More than 50 Percent of prelingual hearing loss is genetic in origin, and of these up to 93 Percent are monogenic autosomal recessive traits. Some forms of genetic deafness can be recognized by their associated syndromic features, but in most cases, hearing loss is the only finding and is referred to as nonsyndromic deafness. To date, more than 700 different mutations have been identified in one of 42 genes in individuals with autosomal recessive nonsyndromic hearing loss (ARNSHL). Reported mutations in GJB2, encoding connexin 26, makes this gene the most common cause of hearing loss in many populations. Other relatively common deafness genes include SLC26A4, MYO15A, OTOF, TMC1, CDH23, and TMPRSS3. In this report we summarize genes and mutations reported in families with ARNSHL. Founder effects were demonstrated for some recurrent mutations but the most significant findings are the extreme locus and allelic heterogeneity and different spectrum of genes and mutations in each population.

  9. Organs as inheritable property?

    PubMed

    Voo, Teck Chuan; Holm, Soren

    2014-01-01

    It has been argued that organs should be treated as individual tradable property like other material possessions and assets, on the basis that this would promote individual freedom and increase efficiency in addressing the shortage of organs for transplantation. If organs are to be treated as property, should they be inheritable? This paper seeks to contribute to the idea of organs as inheritable property by providing a defence of a default of the family of a dead person as inheritors of transplantable organs. In the course of discussion, various succession rules for organs and their justifications will be suggested. We then consider two objections to organs as inheritable property. Our intention here is to provoke further thought on whether ownership of one's body parts should be assimilated to property ownership.

  10. Fine genetic mapping of a gene for autosomal recessive retinitis pigmentosa on chromosome 6p21

    SciTech Connect

    Shugart, Yin Y.; Banerjee, P.; Knowles, J.A.

    1995-08-01

    The inherited retinal degenerations known as retinitis pigmentosa (RP) can be caused by mutations at many different loci and can be inherited as an autosomal recessive, autosomal dominant, or X-linked recessive trait. Two forms of autosomal recessive (arRP) have been reported to cosegregate with mutations in the rhodopsin gene and the beta-subunit of rod phosphodiesterase on chromosome 4p. Genetic linkage has been reported on chromosomes 6p and 1q. In a large Dominican family, we reported an arRp gene near the region of the peripherin/RDS gene. Four recombinations were detected between the disease locus and an intragenic marker derived from peripherin/RDS. 26 refs., 2 figs., 1 tab.

  11. Obstruction of adaptation in diploids by recessive, strongly deleterious alleles.

    PubMed

    Assaf, Zoe June; Petrov, Dmitri A; Blundell, Jamie R

    2015-05-19

    Recessive deleterious mutations are common, causing many genetic disorders in humans and producing inbreeding depression in the majority of sexually reproducing diploids. The abundance of recessive deleterious mutations in natural populations suggests they are likely to be present on a chromosome when a new adaptive mutation occurs, yet the dynamics of recessive deleterious hitchhikers and their impact on adaptation remains poorly understood. Here we model how a recessive deleterious mutation impacts the fate of a genetically linked dominant beneficial mutation. The frequency trajectory of the adaptive mutation in this case is dramatically altered and results in what we have termed a "staggered sweep." It is named for its three-phased trajectory: (i) Initially, the two linked mutations have a selective advantage while rare and will increase in frequency together, then (ii), at higher frequencies, the recessive hitchhiker is exposed to selection and can cause a balanced state via heterozygote advantage (the staggered phase), and (iii) finally, if recombination unlinks the two mutations, then the beneficial mutation can complete the sweep to fixation. Using both analytics and simulations, we show that strongly deleterious recessive mutations can substantially decrease the probability of fixation for nearby beneficial mutations, thus creating zones in the genome where adaptation is suppressed. These mutations can also significantly prolong the number of generations a beneficial mutation takes to sweep to fixation, and cause the genomic signature of selection to resemble that of soft or partial sweeps. We show that recessive deleterious variation could impact adaptation in humans and Drosophila.

  12. Genetics of neurocutaneous disorders: basic principles of inheritance as they apply to neurocutaneous syndromes.

    PubMed

    Dies, Kira A; Sahin, Mustafa

    2015-01-01

    Neurocutaneous disorders vary widely in clinical presentation as well as genetic cause and inheritance pattern. Recent advancements in genetic research have identified many of the causal genes for neurocutaneous disorders, allowing families to receive genetic testing and genetic counseling to better understand carrier risks, recurrence risks for future generations, and reproductive options such as prenatal testing and preimplantation diagnosis. Examples of specific neurocutaneous disorders are utilized to illustrate the various inheritance patterns seen in this heterogeneous group of disorders, including autosomal dominant, autosomal recessive, X-linked dominant, X-linked recessive, de novo, and somatic and germline mosaicism. © 2015 Elsevier B.V. All rights reserved.

  13. Inherited peripheral neuropathies.

    PubMed

    Saporta, Mario A; Shy, Michael E

    2013-05-01

    Charcot-Marie-Tooth (CMT) disease is a heterogeneous group of inherited peripheral neuropathies in which the neuropathy is the sole or primary component of the disorder, as opposed to diseases in which the neuropathy is part of a more generalized neurologic or multisystem syndrome. Because of the great genetic heterogeneity of this condition, it can be challenging for the general neurologist to diagnose patients with specific types of CMT. This article reviews the biology of the inherited peripheral neuropathies, delineates major phenotypic features of the CMT subtypes, and suggest strategies for focusing genetic testing. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Inherited Peripheral Neuropathies

    PubMed Central

    Saporta, Mario A.; Shy, Michael E.

    2013-01-01

    SYNOPSIS Charcot Marie Tooth disease (CMT) is a heterogeneous group of inherited peripheral neuropathies in which the neuropathy is the sole or primary component of the disorder, as opposed to diseases in which the neuropathy is part of a more generalized neurological or multisystem syndrome. Due to the great genetic heterogeneity of this condition, it can be challenging for the general neurologist to diagnose patients with specific types of CMT. Here, we review the biology of the inherited peripheral neuropathies, delineate major phenotypic features of the CMT subtypes and suggest strategies for focusing genetic testing. PMID:23642725

  15. Hereditary sideroblastic anaemia and ataxia: an X linked recessive disorder.

    PubMed

    Pagon, R A; Bird, T D; Detter, J C; Pierce, I

    1985-08-01

    We report two families in which a non-progressive spinocerebellar syndrome and a sideroblastic anaemia are segregating together in an X linked recessive fashion. Four males in two generations of one family and a fifth male from an unrelated family had both conditions. Both the sideroblastic anaemia and the spinocerebellar syndrome differ from those which have previously been reported to be inherited in an X linked recessive manner. The association of these two clinically distinct disorders in two unrelated families suggests that they are either two closely linked loci which have undergone simultaneous mutation or pleiotropic effects of an altered allele at a single locus. All the heterozygous women had normal neurological examinations and normal haematocrits and red cell indices. Some had ring sideroblasts on bone marrow examination, a dimorphic peripheral blood smear, and raised serum free erythrocyte protoporphyrin, suggesting that a proportion of heterozygotes can be detected by appropriate haematological studies.

  16. Mutations of ESPN cause autosomal recessive deafness and vestibular dysfunction

    PubMed Central

    Naz, S; Griffith, A; Riazuddin, S; Hampton, L; Battey, J; Khan, S; Riazuddin, S; Wilcox, E; Friedman, T

    2004-01-01

    We mapped a human deafness locus DFNB36 to chromosome 1p36.3 in two consanguineous families segregating recessively inherited deafness and vestibular areflexia. This phenotype co-segregates with either of two frameshift mutations, 1988delAGAG and 2469delGTCA, in ESPN, which encodes a calcium-insensitive actin-bundling protein called espin. A recessive mutation of ESPN is known to cause hearing loss and vestibular dysfunction in the jerker mouse. Our results establish espin as an essential protein for hearing and vestibular function in humans. The abnormal vestibular phenotype associated with ESPN mutations will be a useful clinical marker for refining the differential diagnosis of non-syndromic deafness. PMID:15286153

  17. Hereditary sideroblastic anaemia and ataxia: an X linked recessive disorder.

    PubMed Central

    Pagon, R A; Bird, T D; Detter, J C; Pierce, I

    1985-01-01

    We report two families in which a non-progressive spinocerebellar syndrome and a sideroblastic anaemia are segregating together in an X linked recessive fashion. Four males in two generations of one family and a fifth male from an unrelated family had both conditions. Both the sideroblastic anaemia and the spinocerebellar syndrome differ from those which have previously been reported to be inherited in an X linked recessive manner. The association of these two clinically distinct disorders in two unrelated families suggests that they are either two closely linked loci which have undergone simultaneous mutation or pleiotropic effects of an altered allele at a single locus. All the heterozygous women had normal neurological examinations and normal haematocrits and red cell indices. Some had ring sideroblasts on bone marrow examination, a dimorphic peripheral blood smear, and raised serum free erythrocyte protoporphyrin, suggesting that a proportion of heterozygotes can be detected by appropriate haematological studies. PMID:4045952

  18. Clinical importance of duodenal recesses with special reference to internal hernias

    PubMed Central

    Rana, Kum Kum; Kakar, Arun; Aggarwal, Satish; Aggrawal, Anil; Kakar, Smita; Borkar, Nitinkumar

    2016-01-01

    Introduction The detailed knowledge of the peritoneal recesses has great significance with respect to internal hernias. The recesses are usually related to rotation and adhesion of abdominal viscera to the posterior abdominal wall and/or the presence of retroperitoneal vessels which raises the serosal fold. The duodenal recesses are usually related to the 3rd and 4th parts of the duodenum. Internal hernias with respect to these recesses are difficult to diagnose clinically and usually noticed at the time of laparotomy. So, the knowledge of these recesses can be valuable to abdominal surgeons. Material and methods The present study was conducted in 100 cases including 10 cadavers, 45 post mortem cases and 45 cases undergoing laparotomy. Results We found superior and inferior duodenal recesses in 28% and 52% respectively, paraduodenal in 12%, mesentericoparietal in 3%, retroduodenal in 2% and duodenojejunal in 18% of cases. Two abnormal duodenojejunal recesses were found, one on the right (instead of the left) of the abdominal aorta, and in the other the opening was directed upwards instead of downwards. The incidence of internal hernias was 3%. Conclusions Thus it was observed that there is low incidence of superior and inferior duodenal recesses, and high incidence of paraduodenal recess. The abnormal recesses might be due to malrotation of the gut. In laparotomy cases, the internal hernia was noticed when the abdomen was opened for intestinal obstruction. The incidence of internal hernia was found to be high. PMID:28144266

  19. Anaesthetic management of a child with congenital afibrinogenemia - A rare inherited coagulation disorder.

    PubMed

    Goyal, Sham Sunder; Bhardwaj, D Vimal; Shenoy, Uk; Reddy, Bhavya

    2011-11-01

    Congenital afibrinogenemia is a very rare autosomal recessive disorder, results from mutation that affects plasma fibrinogen concentration. It is frequently associated with bleeding diathesis of varying severity. We describe the case of a 10-year-old child diagnosed of congenital afibrinogenemia who presented to hospital with subperiosteal haematoma and was posted for incision and drainage. Replacement therapy is the mainstay of treatment of bleeding episodes in this patient and plasma-derived fibrinogen concentrate is the agent of choice. Cryoprecipitate and fresh frozen plasma are alternative treatments. Appropriate amount of cryoprecipitate were transfused pre-operatively to the child. Individuals with congenital afibrinogenemia should be managed by a comprehensive bleeding disorder care team experienced in diagnosing and managing inherited bleeding disorders. Anaesthesiologist, surgeons and haematologist should work like a unit to manage the surgical emergencies.

  20. Anaesthetic management of a child with congenital afibrinogenemia - A rare inherited coagulation disorder

    PubMed Central

    Goyal, Sham Sunder; Bhardwaj, D Vimal; Shenoy, UK; Reddy, Bhavya

    2011-01-01

    Congenital afibrinogenemia is a very rare autosomal recessive disorder, results from mutation that affects plasma fibrinogen concentration. It is frequently associated with bleeding diathesis of varying severity. We describe the case of a 10-year-old child diagnosed of congenital afibrinogenemia who presented to hospital with subperiosteal haematoma and was posted for incision and drainage. Replacement therapy is the mainstay of treatment of bleeding episodes in this patient and plasma-derived fibrinogen concentrate is the agent of choice. Cryoprecipitate and fresh frozen plasma are alternative treatments. Appropriate amount of cryoprecipitate were transfused pre-operatively to the child. Individuals with congenital afibrinogenemia should be managed by a comprehensive bleeding disorder care team experienced in diagnosing and managing inherited bleeding disorders. Anaesthesiologist, surgeons and haematologist should work like a unit to manage the surgical emergencies. PMID:22223906

  1. Hearing loss features in GJB2 biallelic mutations and GJB2/GJB6 digenic inheritance in a large Italian cohort.

    PubMed

    Cama, Elona; Melchionda, Salvatore; Palladino, Teresa; Carella, Massimo; Santarelli, Rosamaria; Genovese, Elisabetta; Benettazzo, Filippo; Zelante, Leopoldo; Arslan, Edoardo

    2009-01-01

    The aim of this study was to describe the clinical features of hearing loss due to mutations on connexin 26/30 coding genes (GJB2/GJB6). Mutations in the GJB2 gene are found to account for approximately 50% of cases of autosomal recessive non-syndromic deafness. Several European studies have estimated that the GJB2 healthy carrier condition involves about 2-4% of the population, with the 35delG mutations being the most common. A 342-kb deletion truncating the GJB6 gene (encoding connexin-30) has been associated with autosomal recessive non-syndromic deafness, mostly as digenic inheritance of the Cx30 deletion/Cx26 mutation. The following retrospective study describes audiological features and genotypes of a large cohort of 376 Italian hearing-impaired patients who underwent genetic screening for the GJB2/GJB6 genes and received follow-up care at our centre between January 2002 and October 2006. Sixteen different genotypes causing deafness in more than 27% of patients with either biallelic mutations or digenic inheritance GJB2/GJB6 were identified. The most frequent mutations were 35delG, M34T, L90P, and R184P.

  2. Hereditary sideroblastic anaemia in 4 siblings of a Libyan family--autosomal inheritance.

    PubMed

    Kasturi, J; Basha, H M; Smeda, S H; Swehli, M

    1982-01-01

    Most of the hereditary sideroblastic anaemias are inherited as x-linked recessive traits and are often pyridoxine responsive. The present paper describes the classical features of sideroblastic anaemia in 2 male and 2 female siblings of a Libyan family. All 4 children had severe anaemia and moderate hepato-splenomegaly. The equal severity of the disease in all 4 family members suggests autosomal inheritance.

  3. Alport syndrome: impact of digenic inheritance in patients management.

    PubMed

    Fallerini, C; Baldassarri, M; Trevisson, E; Morbidoni, V; La Manna, A; Lazzarin, R; Pasini, A; Barbano, G; Pinciaroli, A R; Garosi, G; Frullanti, E; Pinto, A M; Mencarelli, M A; Mari, F; Renieri, A; Ariani, F

    2016-11-08

    Alport syndrome (ATS) is a genetically heterogeneous nephropathy with considerable phenotypic variability and different transmission patterns, including monogenic (X-linked/autosomal) and digenic inheritance (DI). Here we present a new series of families with DI and we discuss the consequences for genetic counseling and risk assessment. Out of five families harboring variants in more than one COL4 gene detected by next generation sequencing (NGS), minigene-splicing assay allowed us to identify four as true digenic. Two families showed COL4A3/A4 mutations in cis, mimicking an autosomal dominant inheritance with a more severe phenotype and one showed COL4A3/A4 mutations in trans, mimicking an autosomal recessive inheritance with a less severe phenotype. In a fourth family, a de novo mutation (COL4A5) combined with an inherited mutation (COL4A3) triggered a more severe phenotype. A fifth family, predicted digenic on the basis of silico tools, rather showed monogenic X-linked inheritance due to a hypomorphic mutation, in accordance with a milder phenotype. In conclusion, this study highlights the impact of DI in ATS and explains the associated atypical presentations. More complex inheritance should be therefore considered when reviewing prognosis and recurrence risks. On the other side, these findings emphasize the importance to accompany NGS with splicing assays in order to avoid erroneous identification of at risk members.

  4. The inheritance of juvenile onset primary open angle glaucoma.

    PubMed

    Gupta, V; Somarajan, B I; Gupta, S; Chaurasia, A K; Kumar, S; Dutta, P; Gupta, V; Sharma, A; Tayo, B O; Nischal, K

    2016-10-25

    Juvenile onset open angle glaucoma (JOAG) affects patients before 40 years of age, who present with high intraocular pressure and deep steep cupping of the optic nerve head. While it was considered to be inherited in an autosomal dominant fashion, recent studies have shown an autosomal recessive pattern as well as sporadic occurrence of the disease in several families. In this review, we analyze the genetic basis of the disease along with common mutations and their association with JOAG. We also analyzed the inheritance patterns in a large group of unrelated JOAG patients (n = 336) from Northern India wherein the prevalence of familial occurrence was assessed and segregation analysis performed, to determine the mode of inheritance.

  5. Non-syndromic, autosomal-recessive deafness.

    PubMed

    Petersen, M B; Willems, P J

    2006-05-01

    Non-syndromic deafness is a paradigm of genetic heterogeneity with 85 loci and 39 nuclear disease genes reported so far. Autosomal-recessive genes are responsible for about 80% of the cases of hereditary non-syndromic deafness of pre-lingual onset with 23 different genes identified to date. In the present article, we review these 23 genes, their function, and their contribution to genetic deafness in different populations. The wide range of functions of these DFNB genes reflects the heterogeneity of the genes involved in hearing and hearing loss. Several of these genes are involved in both recessive and dominant deafness, or in both non-syndromic and syndromic deafness. Mutations in the GJB2 gene encoding connexin 26 are responsible for as much as 50% of pre-lingual, recessive deafness. By contrast, mutations in most of the other DFNB genes have so far been detected in only a small number of families, and their contribution to deafness on a population scale might therefore be limited. Identification of all genes involved in hereditary hearing loss will help in our understanding of the basic mechanisms underlying normal hearing, in early diagnosis and therapy.

  6. Thomsen or Becker myotonia? A novel autosomal recessive nonsense mutation in the CLCN1 gene associated with a mild phenotype.

    PubMed

    Gurgel-Giannetti, Juliana; Senkevics, Adriano S; Zilbersztajn-Gotlieb, Dinorah; Yamamoto, Lydia U; Muniz, Viviane P; Pavanello, Rita C M; Oliveira, Acary B; Zatz, Mayana; Vainzof, Mariz

    2012-02-01

    We describe a large Brazilian consanguineous kindred with 3 clinically affected patients with a Thomsen myotonia phenotype. They carry a novel homozygous nonsense mutation in the CLCN1 gene (K248X). None of the 6 heterozygote carriers show any sign of myotonia on clinical evaluation or electromyography. These findings confirm the autosomal recessive inheritance of the novel mutation in this family, as well as the occurrence of phenotypic variability in the autosomal recessive forms of myotonia.

  7. The molecular basis of inherited afibrinogenaemia.

    PubMed

    Neerman-Arbez, M

    2001-07-01

    This article reviews the substantial progress made in understanding the molecular basis of inherited afibrinogenaemia (or congenital afibrinogenaemia), an autosomal recessive disorder characterised by the complete absence of detectable fibrinogen. The identification in 1999 of the first genetic defect, recurrent homozygous deletions of approximately 11 kb of the fibrinogen alpha-chain (FGA) gene, revealed that the disease was caused by defective fibrinogen synthesis, and led to the subsequent analysis of the three fibrinogen genes in other affected individuals with the identification of numerous causative mutations. Combined analyses of more than thirty unrelated afibrinogenaemia families from various ethnic groups have shown that the majority of patients have truncating mutations in the FGA gene although intuitively all three fibrinogen genes might be equally implicated. These results will facilitate molecular diagnosis of the disorder, permit prenatal diagnosis for families who so desire, and pave the way for new therapeutic approaches such as gene therapy.

  8. New autosomal recessive faciodigitogenital syndrome.

    PubMed Central

    Teebi, A S; Naguib, K K; Al-Awadi, S; Al-Saleh, Q A

    1988-01-01

    Most pedigrees of Aarskog's faciodigitogenital syndrome have suggested X linked inheritance. However, sex influenced autosomal dominant inheritance is also a possibility in some families. We describe an Arab family of normal consanguineous parents with five children (three males and two females) with some features of Aarskog syndrome in addition to some unusual hair changes. The possibility that this family represents a distinct previously unrecognised faciodigitogenital syndrome with short stature and hair abnormalities is suggested and discussed. Images PMID:3398008

  9. Molecular spectrum and differential diagnosis in patients referred with sporadic or autosomal recessive osteogenesis imperfecta.

    PubMed

    Caparros-Martin, Jose A; Aglan, Mona S; Temtamy, Samia; Otaify, Ghada A; Valencia, Maria; Nevado, Julián; Vallespin, Elena; Del Pozo, Angela; Prior de Castro, Carmen; Calatrava-Ferreras, Lucia; Gutierrez, Pilar; Bueno, Ana M; Sagastizabal, Belen; Guillen-Navarro, Encarna; Ballesta-Martinez, Maria; Gonzalez, Vanesa; Basaran, Sarenur Y; Buyukoglan, Ruksan; Sarikepe, Bilge; Espinoza-Valdez, Cecilia; Cammarata-Scalisi, Francisco; Martinez-Glez, Victor; Heath, Karen E; Lapunzina, Pablo; Ruiz-Perez, Victor L

    2017-01-01

    Osteogenesis imperfecta (OI) is a heterogeneous bone disorder characterized by recurrent fractures. Although most cases of OI have heterozygous mutations in COL1A1 or COL1A2 and show autosomal dominant inheritance, during the last years there has been an explosion in the number of genes responsible for both recessive and dominant forms of this condition. Herein, we have analyzed a cohort of patients with OI, all offspring of unaffected parents, to determine the spectrum of variants accounting for these cases. Twenty patients had nonrelated parents and were sporadic, and 21 were born to consanguineous relationships. Mutation analysis was performed using a next-generation sequencing gene panel, homozygosity mapping, and whole exome sequencing (WES). Patients offspring of nonconsanguineous parents were mostly identified with COL1A1 or COL1A2 heterozygous changes, although there were also a few cases with IFITM5 and WNT1 heterozygous mutations. Only one sporadic patient was a compound heterozygote for two recessive mutations. Patients offspring of consanguineous parents showed homozygous changes in a variety of genes including CRTAP,FKBP10,LEPRE1,PLOD2,PPIB,SERPINF1,TMEM38B, and WNT1. In addition, two patients born to consanguineous parents were found to have de novo COL1A1 heterozygous mutations demonstrating that causative variants in the collagen I structural genes cannot be overlooked in affected children from consanguineous couples. Further to this, WES analysis in probands lacking mutations in OI genes revealed deleterious variants in SCN9A,NTRK1, and SLC2A2, which are associated with congenital indifference to pain (CIP) and Fanconi-Bickel syndrome (FBS). This work provides useful information for clinical and genetic diagnosis of OI patients with no positive family history of this disease. Our data also indicate that CIP and FBS are conditions to be considered in the differential diagnosis of OI and suggest a positive role of SCN9A and NTRK1 in bone development.

  10. Plate tectonics, damage and inheritance.

    PubMed

    Bercovici, David; Ricard, Yanick

    2014-04-24

    The initiation of plate tectonics on Earth is a critical event in our planet's history. The time lag between the first proto-subduction (about 4 billion years ago) and global tectonics (approximately 3 billion years ago) suggests that plates and plate boundaries became widespread over a period of 1 billion years. The reason for this time lag is unknown but fundamental to understanding the origin of plate tectonics. Here we suggest that when sufficient lithospheric damage (which promotes shear localization and long-lived weak zones) combines with transient mantle flow and migrating proto-subduction, it leads to the accumulation of weak plate boundaries and eventually to fully formed tectonic plates driven by subduction alone. We simulate this process using a grain evolution and damage mechanism with a composite rheology (which is compatible with field and laboratory observations of polycrystalline rocks), coupled to an idealized model of pressure-driven lithospheric flow in which a low-pressure zone is equivalent to the suction of convective downwellings. In the simplest case, for Earth-like conditions, a few successive rotations of the driving pressure field yield relic damaged weak zones that are inherited by the lithospheric flow to form a nearly perfect plate, with passive spreading and strike-slip margins that persist and localize further, even though flow is driven only by subduction. But for hotter surface conditions, such as those on Venus, accumulation and inheritance of damage is negligible; hence only subduction zones survive and plate tectonics does not spread, which corresponds to observations. After plates have developed, continued changes in driving forces, combined with inherited damage and weak zones, promote increased tectonic complexity, such as oblique subduction, strike-slip boundaries that are subparallel to plate motion, and spalling of minor plates.

  11. Molecular autopsy in victims of inherited arrhythmias.

    PubMed

    Semsarian, Christopher; Ingles, Jodie

    2016-10-01

    Sudden cardiac death (SCD) is a rare but devastating complication of a number of underlying cardiovascular diseases. While coronary artery disease and acute myocardial infarction are the most common causes of SCD in older populations, inherited cardiac disorders comprise a substantial proportion of SCD cases aged less than 40 years. Inherited cardiac disorders include primary inherited arrhythmogenic disorders such as familial long QT syndrome (LQTS), Brugada syndrome (BrS), catecholaminergic polymorphic ventricular tachycardia (CPVT), and inherited cardiomyopathies, most commonly hypertrophic cardiomyopathy (HCM). In up to 40% of young SCD victims (defined as 1-40 years old, excluding sudden unexplained death in infancy from 0 to 1 years, referred to as SIDS), no cause of death is identified at postmortem [so-called "autopsy negative" or "sudden arrhythmic death syndrome" (SADS)]. Management of families following a SCD includes the identification of the cause of death, based either on premorbid clinical details or the pathological findings at the postmortem. When no cause of death is identified, genetic testing of DNA extracted from postmortem tissue (the molecular autopsy) may identify a cause of death in up to 30% of SADS cases. Targeted clinical testing in a specialized multidisciplinary clinic in surviving family members combined with the results from genetic testing, provide the optimal setting for the identification of relatives who may be at risk of having the same inherited heart disease and are therefore also predisposed to an increased risk of SCD.

  12. Lipedema: an inherited condition.

    PubMed

    Child, Anne H; Gordon, Kristiana D; Sharpe, Pip; Brice, Glen; Ostergaard, Pia; Jeffery, Steve; Mortimer, Peter S

    2010-04-01

    Lipedema is a condition characterized by swelling and enlargement of the lower limbs due to abnormal deposition of subcutaneous fat. Lipedema is an under-recognized condition, often misdiagnosed as lymphedema or dismissed as simple obesity. We present a series of pedigrees and propose that lipedema is a genetic condition with either X-linked dominant inheritance or more likely, autosomal dominant inheritance with sex limitation. Lipedema appears to be a condition almost exclusively affecting females, presumably estrogen-requiring as it usually manifests at puberty. Lipedema is an entity distinct from obesity, but may be wrongly diagnosed as primary obesity, due to clinical overlap. The phenotype suggests a condition distinct from obesity and associated with pain, tenderness, and easy bruising in affected areas. (c) 2010 Wiley-Liss, Inc.

  13. Mitochondrial inheritance and disease.

    PubMed

    Fine, P E

    1978-09-23

    Spontaneously occurring variants of the D.N.A. content of mitochondria may be responsible for human disease. Among the prime candidates for such a mitochondrial aetiology are certain drug-induced blood dyscrasias, particularly that due to chloramphenicol. Because mitochondria are generally inherited from the female parent, such disorders should be clustered among matroclinally related individuals. The clinical manifestations of such diseases are a function of the manner in which mitochondria are allocated to somatic cells and tissues during development.

  14. Epigenetic transgenerational inheritance

    PubMed Central

    Skinner, Michael K.

    2017-01-01

    Endocrine disruptors are critical environmental exposures that influence health and can promote epigenetic transgenerational inheritance of disease and abnormal physiology. Advances in 2015 included analyses of the effects of endocrine disruptors on human disease, further examples of endocrine disruptors promoting transgenerational behavioural effects, insights into effects of endocrine disruptors on epigenetic programming of primordial germ cells and the finding that endocrine disruptors can transgenerationally promote genetic mutations. PMID:26585656

  15. Inherited 1q21.1q21.2 duplication and 16p11.2 deletion: a two-hit case with more severe clinical manifestations.

    PubMed

    Brisset, Sophie; Capri, Yline; Briand-Suleau, Audrey; Tosca, Lucie; Gras, Domitille; Fauret-Amsellem, Anne-Laure; Pineau, Dominique; Saada, Julien; Ortonne, Valérie; Verloes, Alain; Goossens, Michel; Tachdjian, Gérard; Métay, Corinne

    2015-09-01

    We report paternally inherited duplication of 1q12q21.2 of 5.8 Mb associated with maternally inherited deletion of 16p11.2 of 545 Kb, this latter first identified in a fetus exhibiting an absent nasal bone detected during pregnancy. During the neonatal period, the young boy presented developmental delay, epilepsy, congenital anomalies and overweight. The clinical features of the proband with two rearrangements were more severe than in either of the parents carrying only one or the other mutation. Thus our data support a two-hit model in which the concomitant presence of these two copy-number variations exacerbates the neurodevelopmental phenotype. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  16. Recessive Resistance to Plant Viruses: Potential Resistance Genes Beyond Translation Initiation Factors.

    PubMed

    Hashimoto, Masayoshi; Neriya, Yutaro; Yamaji, Yasuyuki; Namba, Shigetou

    2016-01-01

    The ability of plant viruses to propagate their genomes in host cells depends on many host factors. In the absence of an agrochemical that specifically targets plant viral infection cycles, one of the most effective methods for controlling viral diseases in plants is taking advantage of the host plant's resistance machinery. Recessive resistance is conferred by a recessive gene mutation that encodes a host factor critical for viral infection. It is a branch of the resistance machinery and, as an inherited characteristic, is very durable. Moreover, recessive resistance may be acquired by a deficiency in a negative regulator of plant defense responses, possibly due to the autoactivation of defense signaling. Eukaryotic translation initiation factor (eIF) 4E and eIF4G and their isoforms are the most widely exploited recessive resistance genes in several crop species, and they are effective against a subset of viral species. However, the establishment of efficient, recessive resistance-type antiviral control strategies against a wider range of plant viral diseases requires genetic resources other than eIF4Es. In this review, we focus on recent advances related to antiviral recessive resistance genes evaluated in model plants and several crop species. We also address the roles of next-generation sequencing and genome editing technologies in improving plant genetic resources for recessive resistance-based antiviral breeding in various crop species.

  17. Recessive Resistance to Plant Viruses: Potential Resistance Genes Beyond Translation Initiation Factors

    PubMed Central

    Hashimoto, Masayoshi; Neriya, Yutaro; Yamaji, Yasuyuki; Namba, Shigetou

    2016-01-01

    The ability of plant viruses to propagate their genomes in host cells depends on many host factors. In the absence of an agrochemical that specifically targets plant viral infection cycles, one of the most effective methods for controlling viral diseases in plants is taking advantage of the host plant’s resistance machinery. Recessive resistance is conferred by a recessive gene mutation that encodes a host factor critical for viral infection. It is a branch of the resistance machinery and, as an inherited characteristic, is very durable. Moreover, recessive resistance may be acquired by a deficiency in a negative regulator of plant defense responses, possibly due to the autoactivation of defense signaling. Eukaryotic translation initiation factor (eIF) 4E and eIF4G and their isoforms are the most widely exploited recessive resistance genes in several crop species, and they are effective against a subset of viral species. However, the establishment of efficient, recessive resistance-type antiviral control strategies against a wider range of plant viral diseases requires genetic resources other than eIF4Es. In this review, we focus on recent advances related to antiviral recessive resistance genes evaluated in model plants and several crop species. We also address the roles of next-generation sequencing and genome editing technologies in improving plant genetic resources for recessive resistance-based antiviral breeding in various crop species. PMID:27833593

  18. Remote Recession Sensing of Ablative Heat Shield Materials

    NASA Technical Reports Server (NTRS)

    Winter, Michael W.; Stackpoole, Margaret; Nawaz, Anuscheh; Gonzales, Gregory Lewis; Ho, Thanh

    2014-01-01

    Material recession and charring are two major processes determining the performance of ablative heat shield materials. Even in ground testing, the characterization of these two mechanisms relies on measurements of material thickness before and after testing, thus providing only information integrated over the test time. For recession measurements, optical methods such as imaging the sample surface during testing are under investigation but require high alignment and instrument effort, therefore being not established as a standard measurement method. For char depth measurements, the most common method so far consists in investigation of sectioned samples after testing or in the case of Stardust where core extractions were performed to determine char information. In flight, no reliable recession measurements are available, except total recession after recovering the heat shield on ground. Developments of mechanical recession sensors have been started but require substantial on board instrumentation adding mass and complexity. In this work, preliminary experiments to evaluate the feasibility of remote sensing of material recession and possibly char depth through optically observing the emission signatures of seeding materials in the post shock plasma is investigated. It is shown that this method can provide time resolved recession measurements without the necessity of accurate alignment procedures of the optical set-up and without any instrumentation on board of a spacecraft. Furthermore, recession data can be obtained without recovering flight hardware which would be a huge benefit for inexpensive heat shield material testing on board of small re-entry probes, e.g. on new micro-satellite re-entry probes as a possible future application of Cubesats or RBR

  19. Familial isolated congenital asplenia: case report and literature review.

    PubMed

    Ahmed, Syed Ather; Zengeya, Stanley; Kini, Usha; Pollard, Andrew J

    2010-03-01

    Congenital asplenia is a rare life-threatening condition, often presenting with pneumococcal sepsis. It may arise as part of situs abnormalities or result from an unrelated specific defect of spleen development. The mode of inheritance is usually autosomal dominant, though sporadic cases are also reported. In affected individuals, the use of appropriate antibiotic prophylaxis and immunisations could save lives. In our report, we describe a family of three siblings with isolated congenital asplenia and unaffected parents, suggestive of recessive inheritance. The diagnosis in the proband was made post mortem following overwhelming pneumococcal sepsis. We also review the literature and compare the eight families previously reported with congenital isolated asplenia.

  20. Algebra, Home Mortgages, and Recessions

    ERIC Educational Resources Information Center

    Mariner, Jean A. Miller; Miller, Richard A.

    2009-01-01

    The current financial crisis and recession in the United States present an opportunity to discuss relevant applications of some topics in typical first-and second-year algebra and precalculus courses. Real-world applications of percent change, exponential functions, and sums of finite geometric sequences can help students understand the problems…

  1. Algebra, Home Mortgages, and Recessions

    ERIC Educational Resources Information Center

    Mariner, Jean A. Miller; Miller, Richard A.

    2009-01-01

    The current financial crisis and recession in the United States present an opportunity to discuss relevant applications of some topics in typical first-and second-year algebra and precalculus courses. Real-world applications of percent change, exponential functions, and sums of finite geometric sequences can help students understand the problems…

  2. Firms Still Training Despite Recession

    ERIC Educational Resources Information Center

    Felstead, Alan; Green, Francis; Jewson, Nick

    2011-01-01

    It is commonly assumed that company training is one of the first casualties in times of recession. Falling recruitment, pressures to cut costs and a focus on short-term survival force businesses to put training on the backburner. Expecting the worst, the UK Commission for Employment and Skills (UKCES), the Confederation of British Industry (CBI)…

  3. Firms Still Training Despite Recession

    ERIC Educational Resources Information Center

    Felstead, Alan; Green, Francis; Jewson, Nick

    2011-01-01

    It is commonly assumed that company training is one of the first casualties in times of recession. Falling recruitment, pressures to cut costs and a focus on short-term survival force businesses to put training on the backburner. Expecting the worst, the UK Commission for Employment and Skills (UKCES), the Confederation of British Industry (CBI)…

  4. Inherited cobalamin malabsorption. Mutations in three genes reveal functional and ethnic patterns.

    PubMed

    Tanner, Stephan M; Sturm, Amy C; Baack, Elizabeth C; Liyanarachchi, Sandya; de la Chapelle, Albert

    2012-08-28

    Inherited malabsorption of cobalamin (Cbl) causes hematological and neurological abnormalities that can be fatal. Three genes have been implicated in Cbl malabsorption; yet, only about 10% of ~400-500 reported cases have been molecularly studied to date. Recessive mutations in CUBN or AMN cause Imerslund-Gräsbeck Syndrome (IGS), while recessive mutations in GIF cause Intrinsic Factor Deficiency (IFD). IGS and IFD differ in that IGS usually presents with proteinuria, which is not observed in IFD. The genetic heterogeneity and numerous differential diagnoses make clinical assessment difficult. We present a large genetic screening study of 154 families or patients with suspected hereditary Cbl malabsorption. Patients and their families have been accrued over a period spanning >12  years. Systematic genetic testing of the three genes CUBN, AMN, and GIF was accomplished using a combination of single strand conformation polymorphism and DNA and RNA sequencing. In addition, six genes that were contenders for a role in inherited Cbl malabsorption were studied in a subset of these patients. Our results revealed population-specific mutations, mutational hotspots, and functionally distinct regions in the three causal genes. We identified mutations in 126/154 unrelated cases (82%). Fifty-three of 126 cases (42%) were mutated in CUBN, 45/126 (36%) were mutated in AMN, and 28/126 (22%) had mutations in GIF. We found 26 undescribed mutations in CUBN, 19 in AMN, and 7 in GIF for a total of 52 novel defects described herein. We excluded six other candidate genes as culprits and concluded that additional genes might be involved. Cbl malabsorption is found worldwide and genetically complex. However, our results indicate that population-specific founder mutations are quite common. Consequently, targeted genetic testing has become feasible if ethnic ancestry is considered. These results will facilitate clinical and molecular genetic testing of Cbl malabsorption. Early diagnosis

  5. Inherited cobalamin malabsorption. Mutations in three genes reveal functional and ethnic patterns

    PubMed Central

    2012-01-01

    Background Inherited malabsorption of cobalamin (Cbl) causes hematological and neurological abnormalities that can be fatal. Three genes have been implicated in Cbl malabsorption; yet, only about 10% of ~400-500 reported cases have been molecularly studied to date. Recessive mutations in CUBN or AMN cause Imerslund-Gräsbeck Syndrome (IGS), while recessive mutations in GIF cause Intrinsic Factor Deficiency (IFD). IGS and IFD differ in that IGS usually presents with proteinuria, which is not observed in IFD. The genetic heterogeneity and numerous differential diagnoses make clinical assessment difficult. Methods We present a large genetic screening study of 154 families or patients with suspected hereditary Cbl malabsorption. Patients and their families have been accrued over a period spanning >12 years. Systematic genetic testing of the three genes CUBN, AMN, and GIF was accomplished using a combination of single strand conformation polymorphism and DNA and RNA sequencing. In addition, six genes that were contenders for a role in inherited Cbl malabsorption were studied in a subset of these patients. Results Our results revealed population-specific mutations, mutational hotspots, and functionally distinct regions in the three causal genes. We identified mutations in 126/154 unrelated cases (82%). Fifty-three of 126 cases (42%) were mutated in CUBN, 45/126 (36%) were mutated in AMN, and 28/126 (22%) had mutations in GIF. We found 26 undescribed mutations in CUBN, 19 in AMN, and 7 in GIF for a total of 52 novel defects described herein. We excluded six other candidate genes as culprits and concluded that additional genes might be involved. Conclusions Cbl malabsorption is found worldwide and genetically complex. However, our results indicate that population-specific founder mutations are quite common. Consequently, targeted genetic testing has become feasible if ethnic ancestry is considered. These results will facilitate clinical and molecular genetic testing of

  6. Hereditary Hypohidrotic Ectodermal Dysplasia: Report of a Rare Case

    PubMed Central

    Paramkusam, Geetha; Meduri, Venkateswarlu; Nadendla, Lakshmi Kavitha; Shetty, Namratha

    2013-01-01

    Hereditary Hypohidrotic Ectodermal Dysplasia (HHED), an X-linked, recessive, Mendelian character, is seen usually in males and it is inherited through female carriers. It is characterised by congenital dysplasia of one or more ectodermal structures and it is manifested by hypohidrosis, hypotrichosis and hypodontia. It results from abnormal morphogenesis of cutaneous and oral embryonic ectoderm. Here, we are presenting a rare case of HHED in a 19 year female with classic features of this condition. PMID:24179947

  7. Fractional populations in sex-linked inheritance

    NASA Astrophysics Data System (ADS)

    Pyo Lee, Seung; Chung, Myung-Hoon; Koo Kim, Chul; Nahm, Kyun

    2001-03-01

    We study the fractional populations in chromosome inherited diseases. The governing equations for the fractional populations are found and solved in the presence of mutation and selection. The physical fixed points obtained are used to discuss the cases of color blindness and hemophilia.

  8. Straight thinking about groundwater recession

    NASA Astrophysics Data System (ADS)

    Cuthbert, M. O.

    2014-03-01

    While in catchment and hillslope hydrology a more nuanced approach is now taken to streamflow recession analysis, in the context of major aquifers it is commonly still assumed that the groundwater head recession rate will take exponential form, an idea originally proposed in the 19th Century. However it is shown here that, in early times, the groundwater head recession in a major aquifer should take an almost straight line form with a rate approximately equal to the long-term recharge rate divided by the aquifer storage coefficient. The length of this phase can be estimated from an analytical expression derived in the paper which depends on the aquifer diffusivity, length scale, and the position of the monitoring point. A transitional phase then leads to an exponential phase after some critical time which is independent of the position of the monitoring point. Major aquifers in a state of periodic quasi-steady state are expected to have rates of groundwater flux recession which deviate little from the average rate of groundwater recharge. Where quasi-exponential groundwater declines are observed in nature, their form may be diagnostic of particular types of aquifer properties and/or boundary effects, such as proximity to drainage boundaries, variations in transmissivity with hydraulic head, storage changes due to pumping, nonequilibrium flow at a range of spatial and temporal scales, and variations in specific yield with depth. Recession analysis has applicability to a range of groundwater problems and is powerful way of gaining insight into the hydrologic functioning of an aquifer.

  9. Inherited epidermolysis bullosa: clinical and therapeutic aspects*

    PubMed Central

    Boeira, Vanessa Lys Simas Yamakawa; Souza, Erica Sales; Rocha, Bruno de Oliveira; Oliveira, Pedro Dantas; de Oliveira, Maria de Fátima Santos Paim; Rêgo, Vitória Regina Pedreira de Almeida; Follador, Ivonise

    2013-01-01

    Inherited epidermolysis bullosa (EB) is a heterogeneous group of genetic disorders that present with skin and, in some cases, mucosal fragility, predisposing patients to the development of blisters and/or erosions after minimal trauma or friction. Children with a recurrent history of these kinds of lesions or neonates that present them in the absence of another reasonable explanation should be investigated. Diagnosis must be based on clinical and histopathological findings. To date, management of inherited EB basically consists in avoiding traumas that trigger lesions, as well as preventing infection and facilitating healing of the wounds with the systematic use of bandages. PMID:23739692

  10. [Inheritance analysis of resistant starch content in kernels of wheat].

    PubMed

    Pang, Huan; Li, Wei-Hua; Zhang, Hong-Bin; Wang, Lin; Yin, Yong-An; Yuan, Hui-Gong; Wang, Zi-Bu

    2010-02-01

    In this study, three wheat (Triticum aestivum L.) cultivars with high and low levels of resistant starch contents each were selected to obtain 15 F1 combinations from a diallel cross without reciprocals to be used to study the inheritance of resistant starch content. The results of this study are useful to select new wheat cultivar with high level of resistant starch content. Annong 90202 and D68-20 were the best among the wheat cultivars tested for general combining ability of resistant starch content, which significantly increased the resistant starch content in its progenies. The specific combining ability of Annong 90202 x 04 Dan 28 and 06-5 x D68-20 were the best among the F1 combinations, and the values of specific combining ability effects were significantly higher than other combinations. The inheritance of resistant starch content fitted the additive-dominance model, and the degree of dominance was super dominance. The alleles for increasing resistant starch content were recessive. The distribution of alleles for increasing and reducing resistant starch contents in the parental lines was not even. The number of recessive alleles for resistant starch content was greater than the dominant alleles. Annong 90202 and 04 Dan 28 had more recessive genes controlling resistant starch content, while Ningchun 18 and Xinchun 5 had more dominant genes. The narrow sense heritability of resistant starch content was 36.49%.

  11. [Genetic diagnostic testing in inherited retinal dystrophies].

    PubMed

    Kohl, S; Biskup, S

    2013-03-01

    Inherited retinal dystrophies are clinically and genetically highly heterogeneous. They can be divided according to the clinical phenotype and course of the disease, as well as the underlying mode of inheritance. Isolated retinal dystrophies (i.e., retinitis pigmentosa, Leber's congenital amaurosis, cone and cone-rod dystrophy, macular dystrophy, achromatopsia, congenital stationary nightblindness) and syndromal forms (i.e., Usher syndrome, Bardet-Biedl syndrome) can be differentiated. To date almost 180 genes and thousands of distinct mutations have been identified that are responsible for the different forms of these blinding illnesses. Until recently, there was no adequate diagnostic genetic testing available. With the development of the next generation sequencing technologies, a comprehensive genetic screening analysis for all known genes for inherited retinal dystrophies has been established at reasonable costs and in appropriate turn-around times. Depending on the primary clinical diagnosis and the presumed mode of inheritance, different diagnostic panels can be chosen for genetic testing. Statistics show that in 55-80 % of the cases the genetic defect of the inherited retinal dystrophy can be identified with this approach, depending on the initial clinical diagnosis. The aim of any genetic diagnostics is to define the genetic cause of a given illness within the affected patient and family and thereby i) confirm the clinical diagnosis, ii) provide targeted genetic testing in family members, iii) enable therapeutic intervention, iv) give a prognosis on disease course and progression and v) in the long run provide the basis for novel therapeutic approaches and personalised medicine.

  12. A bird's eye view of a deleterious recessive allele.

    PubMed

    Ekblom, Robert

    2016-07-01

    In the endangered Scottish chough (Pyrrhocorax pyrrhocorax) population, a lethal blindness syndrome is found to be caused by a deleterious recessive allele. Photo: Gordon Yates. In Focus: Trask, A.E., Bignal, E.M., McCracken, D.I., Monaghan, P., Piertney, S.B. & Reid, J.M. (2016) Evidence of the phenotypic expression of a lethal recessive allele under inbreeding in a wild population of conservation concern. Journal of Animal Ecology, 85, 879-891. In this issue of Journal of Animal Ecology, Trask et al. () report on a strange, lethal, blindness that regularly affects chicks of an endangered bird population. The authors show that the inheritance mode of this blindness disease precisely matches the expectations of a recessive deleterious mutation. Intriguingly, there is also an indication that the disease-causing variant might be maintained in the population by balancing selection, due to a selective advantage for heterozygotes. Could this finding have consequences for conservation actions implemented for the population?

  13. Gene Therapy of Inherited Retinopathies: A Long and Successful Road from Viral Vectors to Patients

    PubMed Central

    Colella, Pasqualina

    2012-01-01

    Abstract Inherited retinopathies (IRs) are common and untreatable blinding conditions inherited mostly as monogenic due to mutations in genes expressed in retinal photoreceptors (PRs) and in retinal pigment epithelium (RPE). Over the last two decades, the retina has emerged as one of the most favorable target tissues for gene therapy given its small size and its enclosed and immune-privileged environment. Different types of viral vectors have been developed, especially those based on the adeno-associated virus (AAV), which efficiently deliver therapeutic genes to PRs or RPE upon subretinal injections. Dozens of successful proofs of concept of the efficacy of gene therapy for recessive and dominant IRs have been generated in small and large models that have paved the way to the first clinical trials using AAV in patients with Leber congenital amaurosis, a severe form of childhood blindness. The results from these initial trials suggest that retinal gene therapy with AAV is safe in humans, that vision can be improved in patients that have suffered from severe impairment of visual function, in some cases for decades, and that readministration of AAV to the subretinal space is feasible, effective, and safe. However, none of the trials could match the levels of efficacy of gene therapy observed in a dog model of the disease, suggesting that there is room for improvement. In conclusion, these results bode well for further testing of AAV-mediated retinal gene therapy in patients with other monogenic and complex forms of blindness. PMID:22734691

  14. Gene therapy of inherited retinopathies: a long and successful road from viral vectors to patients.

    PubMed

    Colella, Pasqualina; Auricchio, Alberto

    2012-08-01

    Inherited retinopathies (IRs) are common and untreatable blinding conditions inherited mostly as monogenic due to mutations in genes expressed in retinal photoreceptors (PRs) and in retinal pigment epithelium (RPE). Over the last two decades, the retina has emerged as one of the most favorable target tissues for gene therapy given its small size and its enclosed and immune-privileged environment. Different types of viral vectors have been developed, especially those based on the adeno-associated virus (AAV), which efficiently deliver therapeutic genes to PRs or RPE upon subretinal injections. Dozens of successful proofs of concept of the efficacy of gene therapy for recessive and dominant IRs have been generated in small and large models that have paved the way to the first clinical trials using AAV in patients with Leber congenital amaurosis, a severe form of childhood blindness. The results from these initial trials suggest that retinal gene therapy with AAV is safe in humans, that vision can be improved in patients that have suffered from severe impairment of visual function, in some cases for decades, and that readministration of AAV to the subretinal space is feasible, effective, and safe. However, none of the trials could match the levels of efficacy of gene therapy observed in a dog model of the disease, suggesting that there is room for improvement. In conclusion, these results bode well for further testing of AAV-mediated retinal gene therapy in patients with other monogenic and complex forms of blindness.

  15. [Anesthesia for cesarean section in a patient with recessive dystrophic epidermolysis bullosa].

    PubMed

    García, I; Manrique, S; Muñoz, C; López-Gil, M V; Munar, F; Montferrer, N

    2009-11-01

    Recessive dystrophic epidermolysis bullosa is inherited as a rare autosomal disorder which causes blisters to form in the skin. We describe the treatment of a 39-year-old parturient with this condition. She was scheduled for elective cesarean section at 37 weeks' gestation. The patient had widespread skin lesions, had lost fingers, and had esophageal stenosis. The cesarean was performed under spinal anesthesia without complications. Recessive dystrophic epidermolysis bullosa requires adaptation of anesthetic technique that includes control over posture and careful handling of the skin. Material for attaching monitoring devices and inserting venous lines must be adapted to the particular deformities and skin lesions present.

  16. Exercise and Inherited Arrhythmias.

    PubMed

    Cheung, Christopher C; Laksman, Zachary W M; Mellor, Gregory; Sanatani, Shubhayan; Krahn, Andrew D

    2016-04-01

    Sudden cardiac death (SCD) in an apparently healthy individual is a tragedy that prompts a series of investigations to identify the cause of death and to prevent SCD in potentially at-risk family members. Several inherited channelopathies and cardiomyopathies, including long QT syndrome (LQTS), catecholaminergic polymorphic ventricular cardiomyopathy (CPVT), hypertrophic cardiomyopathy (HCM), and arrhythmogenic right ventricular cardiomyopathy (ARVC) are associated with exercise-related SCD. Exercise restriction has been a historical mainstay of therapy for these conditions. Syncope and cardiac arrest occur during exercise in LQTS and CPVT because of ventricular arrhythmias, which are managed with β-blockade and exercise restriction. Exercise may provoke hemodynamic or ischemic changes in HCM, leading to ventricular arrhythmias. ARVC is a disease of the desmosome, whose underlying disease process is accelerated by exercise. On this basis, expert consensus has erred on the side of caution, recommending rigorous exercise restriction for all inherited arrhythmias. With time, as familiarity with inherited arrhythmia conditions has increased and patients with milder forms of disease are diagnosed, practitioners have questioned the historical rigorous restrictions advocated for all. This change has been driven by the fact that these are often children and young adults who wish to lead active lives. Recent evidence suggests a lower risk of exercise-related arrhythmias in treated patients than was previously assumed, including those with previous symptoms managed with an implantable cardioverter-defibrillator. In this review, we emphasize shared decision making, monitored medical therapy, individual and team awareness of precautions and emergency response measures, and a more permissive approach to recreational and competitive exercise.

  17. Ventricular arrhythmias in Rhodesian Ridgebacks with a family history of sudden death and results of a pedigree analysis for potential inheritance patterns.

    PubMed

    Meurs, Kathryn M; Weidman, Jess A; Rosenthal, Steven L; Lahmers, Kevin K; Friedenberg, Steven G

    2016-05-15

    OBJECTIVE To evaluate a group of related Rhodesian Ridgebacks with a family history of sudden death for the presence of arrhythmia and to identify possible patterns of disease inheritance among these dogs. DESIGN Prospective case series and pedigree investigation. ANIMALS 25 Rhodesian Ridgebacks with shared bloodlines. PROCEDURES Pedigrees of 4 young dogs (1 female and 3 males; age, 7 to 12 months) that died suddenly were evaluated, and owners of closely related dogs were asked to participate in the study. Dogs were evaluated by 24-hour Holter monitoring, standard ECG, echocardiography, or some combination of these to assess cardiac status. Necropsy reports, if available, were reviewed. RESULTS 31 close relatives of the 4 deceased dogs were identified. Of 21 dogs available for examination, 8 (2 males and 6 females) had ventricular tachyarrhythmias (90 to 8,700 ventricular premature complexes [VPCs]/24 h). No dogs had clinical signs of cardiac disease reported. Echocardiographic or necropsy evaluation for 7 of 12 dogs deemed affected (ie, with frequent or complex VPCs or sudden death) did not identify structural lesions. Five of 6 screened parents of affected dogs had 0 to 5 VPCs/24 h (all singlets), consistent with a normal reading. Pedigree evaluation suggested an autosomal recessive pattern of inheritance, but autosomal dominant inheritance with incomplete penetrance could not be ruled out. CONCLUSIONS AND CLINICAL RELEVANCE Holter monitoring of Rhodesian Ridgebacks with a family history of an arrhythmia or sudden death is recommended for early diagnosis of disease. An autosomal recessive pattern of inheritance in the studied dogs was likely, and inbreeding should be strongly discouraged.

  18. Advances in the treatment of inherited coagulation disorders.

    PubMed

    Escobar, M A

    2013-09-01

    Inherited coagulation disorders constitute a broad spectrum of coagulation factor deficiencies that include X-linked factor (F)VIII or FIX deficiency that causes haemophilia, and autosomal recessive disorders producing heterogeneous deficiencies in fibrinogen (FI), prothrombin (FII), FV, FVII, FX, FXI, FXIII and combined FV+FVIII. Significant advances in treatments for patients with congenital haemophilia A (FVIII deficiency) and B (FIX deficiency) over the last two decades have resulted from improvements in the production, availability and patient access to factor replacement products. Translation of advances in biotechnology, namely recombinant protein technology, targeted protein modifications to improve function and potentially reduce immunogenicity, and advanced formulations to optimize bioavailability and sustain activity offer promisingly new treatments for haemophilia as well as recessively inherited bleeding disorders in patients who otherwise have few therapeutic options. Though a theoretical risk remains for blood-borne viral infections with pooled plasma-derived products, this concern has diminished with breakthroughs in purification and viral inactivation methods. Development of inhibitory antibodies is still the most daunting problem for patients with inherited bleeding disorders, complicating treatment approaches to control and prevent bleeding, and posing risks for allergic and anaphylactic reactions in susceptible patients. The objectives of this review are to (i) highlight emerging advances in hemostatic therapies that are bioengineered to improve pharmacokinetic properties and bioavailability, sustain functional activity, and possibly eliminate immunogenicity of recombinant factor proteins; and (ii) present an overview of key clinical trials of novel factor products currently in the development pipeline.

  19. The inherited ataxias: genetic heterogeneity, mutation databases, and future directions in research and clinical diagnostics.

    PubMed

    Hersheson, Joshua; Haworth, Andrea; Houlden, Henry

    2012-09-01

    The inherited cerebellar ataxias are a diverse group of clinically and genetically heterogeneous neurodegenerative disorders. Inheritance patterns of these disorders can be complex with autosomal dominant, autosomal recessive, X-linked, and mitochondrial inheritance demonstrated by one or more ataxic syndromes. The broad range of mutation types found in inherited ataxia contributes to the complex genetic etiology of these disorders. The majority of inherited ataxias are caused by repeat expansions; however, conventional mutations are important causes of the rarer dominant and recessive ataxias. Advances in sequencing technology have allowed for much broader testing of these rare ataxia genes. This is relevant to the aims of the Human Variome Project, which aims to collate and store gene variation data through mutation databases. Variant data is currently located in a range of public and commercial resources. Few locus-specific databases have been created to catalogue variation in the dominant ataxia genes although there are several databases for some recessive genes. Developing these resources will facilitate a better understanding of the complex genotype-phenotype relationships in these disorders and assist interpretation of gene variants as testing for rarer ataxia genes becomes commonplace.

  20. Differences in Physical Activity during School Recess

    ERIC Educational Resources Information Center

    Ridgers, Nicola D.; Saint-Maurice, Pedro F.; Welk, Gregory J.; Siahpush, Mohammad; Huberty, Jennifer

    2011-01-01

    Background: School recess provides a daily opportunity for physical activity engagement. The purpose of this study was to examine physical activity levels during recess by gender, ethnicity, and grade, and establish the contribution of recess to daily school physical activity levels. Methods: Two hundred and ten children (45% boys) from grades 3…

  1. Hepatitic inherited metabolic disorders.

    PubMed

    Arroyo, May; Crawford, James M

    2006-01-01

    Primary metabolic disorders are a disparate group of diseases that may or may not be accompanied by hepatic manifestations. Those with liver involvement may show a range of histopathologic changes. Proper histologic diagnosis requires correlation with clinical and laboratory data, including evaluation for mutations either via serum protein electrophoresis or through formal genetic analysis. This article is a review of the three most common inherited metabolic disorders which may present with a hepatitic pattern. In alpha1-antitrypsin disorder, there is a broad range of clinical presentations, age at presentation, and histological features ranging from "neonatal hepatitis" to a chronic progressive hepatitis in later childhood and adulthood. Hence, this disorder must be in the differential diagnosis of liver disease of the very young, and in older children and adults, with or without coexistent overt pulmonary symptoms. In Wilson disease, presentation tends to be in older childhood or the adult, with a progressive chronic hepatitis. Cystic fibrosis may feature a characteristic obstructive biliary syndrome, coexisting with the many extrahepatic manifestations of this debilitating disease. Lastly, the progressive familial intrahepatic cholestasis (PFIC) syndromes are given as examples of inherited metabolic conditions in which relentlessly progressive cholestatic liver disease eventuates over years in end-stage cholestatic liver disease with cirrhosis. Distinguishing features include absence of elevated serum gamma-glutamyl transpeptidase (GGT) in PFIC-1 and PFIC-2, and elevated GGT in PFIC-3. However, molecular studies are required for a confident diagnosis of the rare PFIC syndromes.

  2. Inherited mitochondrial disorders.

    PubMed

    Finsterer, Josef

    2012-01-01

    Though inherited mitochondrial disorders (MIDs) are most well known for their syndromic forms, for which widely known acronyms (MELAS, MERRF, NARP, LHON etc.) have been coined, the vast majority of inherited MIDs presents in a non-syndromic form. Since MIDs are most frequently multisystem disorders already at onset or during the disease course, a MID should be suspected if there is a combination of neurological and non-neurological abnormalities. Neurological abnormalities occurring as a part of a MID include stroke-like episodes, epilepsy, migraine-like headache, movement disorders, cerebellar ataxia, visual impairment, encephalopathy, cognitive impairment, dementia, psychosis, hypopituitarism, aneurysms, or peripheral nervous system disease, such as myopathy, neuropathy, or neuronopathy. Non-neurological manifestations concern the ears, the endocrine organs, the heart, the gastrointestinal tract, the kidneys, the bone marrow, and the skin. Whenever there is an unexplained combination of neurological and non-neurological disease in a patient or kindred, a MID should be suspected and appropriate diagnostic measures initiated. Genetic testing should be guided by the phenotype, the biopsy findings, and the biochemical results.

  3. Inherited predisposition to myeloproliferative neoplasms

    PubMed Central

    Jones, Amy V.

    2013-01-01

    Myeloproliferative neoplasms (MPNs) are haematological disorders characterized by an overproduction of mature myeloid cells with a tendency to transform to acute myeloid leukaemia. Clonal proliferation of myeloid progenitor cells is driven by somatically acquired mutations, most notably JAK2 V617F, but there are important features relating to pathogenesis and phenotypic diversity that cannot be explained by acquired mutations alone. In this review we consider what is currently known about the role that inherited factors play in the development and biology of both sporadic and familial forms of MPN. Although most MPN cases appear to be sporadic, familial predisposition has been recognized for many years in a subset of cases and epidemiological studies have indicated the presence of common susceptibility alleles. Currently the JAK2 46/1 haplotype (also referred to as ‘GGCC’) is the strongest known predisposition factor for sporadic MPNs carrying a JAK2 V617F mutation, explaining a large proportion of the heritability of this disorder. Less is known about what genetic variants predispose to MPNs that lack JAK2 V617F, but there have been recent reports of interesting associations in biologically plausible candidates, and more loci are set to emerge with the application of systematic genome-wide association methodologies. Several highly penetrant predisposition variants that affect erythropoietin signalling, thrombopoietin signalling or oxygen sensing have been characterized in families with nonclonal hereditary erythrocytosis or thrombocytosis, but much less is known about familial predisposition to true clonal MPN. The heterogeneous pattern of inheritance and presumed genetic heterogeneity in these families makes analysis difficult, but whole exome or genome sequencing should provide novel insights into these elusive disorders. PMID:23926457

  4. Gingival recession in postmenopausal women with and without osteoporosis

    PubMed Central

    DUNCEA, IOANA; POP, DAN; GEORGESCU, CARMEN

    2013-01-01

    Background The periodontal disease is a complex chronic progressive inflammatory and destructive process of the tooth attachment apparatus: gingiva, alveolar bone, desmodontium, cementum. Systemic osteoporosis has a potential influence on both the periodontal and gingival inflammation indices, on the gingival recession (GR) and teeth mobility. The aim of this study was to investigate the possible relationship between the menopause osteoporosis and gingival recession, by studying the correlations between osteoporosis and gingival recession, and between the bone mineral density (BMD) at the level of L1–L4, femur, hip, mandible and gum recession. Materials and methods The present study included a total of 97 postmenopausal patients. The diagnosis of osteoporosis was made based on the WHO definition. The results were expressed as absolute BMD values in g/cm2 and as T score form. We used dual x-ray absortiometry (DXA) measurements in assessing the lumbar column, proximal femur and mandible and we calculated the T scores. The gingival recession, which is an indicator of ligament tissue lysis and apical migration of the periodontal tissue, was measured as the distance between the anatomical tooth neck and the gumline. For the statistical analysis the Medcalc program version 12.3 was used. Results We found statistically significant differences between the two groups of women, with and without osteoporosis, in terms of the distribution of the cases of GR (p=0.003). The only parameter with statistical significance of the differences between the three categories of gingival recessions (absent, moderate, major), was p=0.034 for the femoral neck BMD. There were significant differences between the mean values of lumbar column L1–L4 BMD according to the presence or absence of recession signs. Conclusions 1) The prevalence of moderate and major gingival recession was statistically significantly higher in the group of postmenopausal women with osteoporosis. 2) In postmenopausal

  5. Inherited factor V deficient neonate with galactosaemia.

    PubMed

    Mansouritorghabeh, Hassan; Sharifi-Hoseini, Mohamad Reza; Shahroudian, Masoud

    2012-03-01

    Reporting a case of inherited factor V deficiency and galactosemia. A neonate was admitted with hematoma, jaundice, splenomegaly, diarrhea, anemia, abdominal ascites and bilateral cataracts that diagnosis of galactosaemia and factor V deficiency was established. Coinheritance of both coagulation disorder and metabolic disorder is very rare episode that was identified in a neonate. Our case indicates that in mild bleeding episodes of neonates that imitate of coagulation disorders should be considered promptly by pediatricians. Copyright © 2012. Published by Elsevier Inc.

  6. Are streamflow recession characteristics really characteristic?

    NASA Astrophysics Data System (ADS)

    Stoelzle, M.; Stahl, K.; Weiler, M.

    2013-02-01

    Streamflow recession has been investigated by a variety of methods, often involving the fit of a model to empirical recession plots to parameterize a non-linear storage-outflow relationship based on the dQ/dt-Q method. Such recession analysis methods (RAMs) are used to estimate hydraulic conductivity, storage capacity, or aquifer thickness and to model streamflow recession curves for regionalization and prediction at the catchment scale. Numerous RAMs have been published, but little is known about how comparably the resulting recession models distinguish characteristic catchment behavior. In this study we combined three established recession extraction methods with three different parameter-fitting methods to the power-law storage-outflow model to compare the range of recession characteristics that result from the application of these different RAMs. Resulting recession characteristics including recession time and corresponding storage depletion were evaluated for 20 meso-scale catchments in Germany. We found plausible ranges for model parameterization; however, calculated recession characteristics varied over two orders of magnitude. While recession characteristics of the 20 catchments derived with the different methods correlate strongly, particularly for the RAMs that use the same extraction method, not all rank the catchments consistently, and the differences among some of the methods are larger than among the catchments. To elucidate this variability we discuss the ambiguous roles of recession extraction procedures and the parameterization of the storage-outflow model and the limitations of the presented recession plots. The results suggest strong limitations to the comparability of recession characteristics derived with different methods, not only in the model parameters but also in the relative characterization of different catchments. A multiple-methods approach to investigating streamflow recession characteristics should be considered for applications

  7. Are streamflow recession characteristics really characteristic?

    NASA Astrophysics Data System (ADS)

    Stoelzle, M.; Stahl, K.; Weiler, M.

    2012-09-01

    Streamflow recession has been investigated by a variety of methods, often involving the fit of a model to empirical recession plots to parameterize a non-linear storage-outflow relationship. Such recession analysis methods (RAMs) are used to estimate hydraulic conductivity, storage capacity, or aquifer thickness and to model streamflow recession curves for regionalization and prediction at the catchment scale. Numerous RAMs have been published, but little is known about how characteristic the resulting recession models are to distinguish characteristic catchment behavior. In this study we combined three established recession extraction methods with three different parameter-fitting methods to the power-law storage-outflow model to compare the range of recession characteristics that result from the application of these different RAMs. Resulting recession characteristics including recession time and corresponding storage depletion were evaluated for 20 meso-scale catchments in Germany. We found plausible ranges for model parameterization, however, calculated recession characteristics varied over two orders of magnitude. While recession characteristics of the 20 catchments derived with the different methods correlate strongly, particularly for the RAMs that use the same extraction method and while they rank the catchments relatively consistent, there are still considerable differences among the methods. To elucidate this variability we discuss the ambiguous roles of recession extraction procedures and the parameterization of storage-outflow model and the limitations of the presented recession plots. The results suggest strong limitations to the comparability of recession characteristics derived with different methods, not only in the model parameters but also in the relative characterization of different catchments. A multiple methods approach to investigate streamflow recession characteristics should be considered for applications whenever possible.

  8. Obstruction of adaptation in diploids by recessive, strongly deleterious alleles

    PubMed Central

    Assaf, Zoe June; Petrov, Dmitri A.; Blundell, Jamie R.

    2015-01-01

    Recessive deleterious mutations are common, causing many genetic disorders in humans and producing inbreeding depression in the majority of sexually reproducing diploids. The abundance of recessive deleterious mutations in natural populations suggests they are likely to be present on a chromosome when a new adaptive mutation occurs, yet the dynamics of recessive deleterious hitchhikers and their impact on adaptation remains poorly understood. Here we model how a recessive deleterious mutation impacts the fate of a genetically linked dominant beneficial mutation. The frequency trajectory of the adaptive mutation in this case is dramatically altered and results in what we have termed a “staggered sweep.” It is named for its three-phased trajectory: (i) Initially, the two linked mutations have a selective advantage while rare and will increase in frequency together, then (ii), at higher frequencies, the recessive hitchhiker is exposed to selection and can cause a balanced state via heterozygote advantage (the staggered phase), and (iii) finally, if recombination unlinks the two mutations, then the beneficial mutation can complete the sweep to fixation. Using both analytics and simulations, we show that strongly deleterious recessive mutations can substantially decrease the probability of fixation for nearby beneficial mutations, thus creating zones in the genome where adaptation is suppressed. These mutations can also significantly prolong the number of generations a beneficial mutation takes to sweep to fixation, and cause the genomic signature of selection to resemble that of soft or partial sweeps. We show that recessive deleterious variation could impact adaptation in humans and Drosophila. PMID:25941393

  9. Fine genetic mapping of Cp, a recessive gene for compact (dwarf) plant architecture in cucumber, cucumis sativus L

    USDA-ARS?s Scientific Manuscript database

    The compact or dwarf plant architecture is an important trait in cucumber breeding. Compact cucumber has the potential to be used in once-over mechanical harvest of pickling cucumber production. Compact growth habit is controlled by a simply inherited recessive gene. To facilitate markers assisted s...

  10. Dominantly-inherited lop ears.

    PubMed

    Leung, Alexander K C; Kong, Albert Y F; Robson, W Lane M; McLeod, D Ross

    2007-10-01

    We describe a four-generation Chinese family that included five members who had an isolated bilateral lop ear anomaly. The presentation suggested a dominant mode of inheritance. The absence of male-to-male transmission does not exclude an X-linked dominant mode of inheritance. Since the phenotypic anomaly of the male proband was no more severe than the affected female members, an autosomal dominant mode of inheritance is most likely. 2007 Wiley-Liss, Inc

  11. HDR: a statistical two-step approach successfully identifies disease genes in autosomal recessive families.

    PubMed

    Imai, Atsuko; Kohda, Masakazu; Nakaya, Akihiro; Sakata, Yasushi; Murayama, Kei; Ohtake, Akira; Lathrop, Mark; Okazaki, Yasushi; Ott, Jurg

    2016-11-01

    In the search for sequence variants underlying disease, commonly applied filtering steps usually result in a number of candidate variants that cannot further be narrowed down. In autosomal recessive families, disease usually occurs only in one generation so that genetic linkage analysis is unlikely to help. Because homozygous recessive mutations tend to be inherited together with flanking homozygous variants, we developed a statistical method to detect pathogenic variants in autosomal recessive families: We look for differences in patterns of homozygosity around candidate variants between patients and control individuals and expect that such differences are greater for pathogenic variants than random candidate variants. In six autosomal recessive mitochondrial disease families, in which pathogenic homozygous variants have already been identified, our approach succeeded in prioritizing pathogenic mutations. Our method is applicable to single patients from recessive families with at least a few dozen control individuals from the same population; it is easy to use and is highly effective for detecting causative mutations in autosomal recessive families.

  12. Autozygosity reveals recessive mutations and novel mechanisms in dominant genes: implications in variant interpretation.

    PubMed

    Monies, Dorota; Maddirevula, Sateesh; Kurdi, Wesam; Alanazy, Mohammed H; Alkhalidi, Hisham; Al-Owain, Mohammed; Sulaiman, Raashda A; Faqeih, Eissa; Goljan, Ewa; Ibrahim, Niema; Abdulwahab, Firdous; Hashem, Mais; Abouelhoda, Mohamed; Shaheen, Ranad; Arold, Stefan T; Alkuraya, Fowzan S

    2017-10-01

    The purpose of this study is to describe recessive alleles in strictly dominant genes. Identifying recessive mutations in genes for which only dominant disease or risk alleles have been reported can expand our understanding of the medical relevance of these genes both phenotypically and mechanistically. The Saudi population is enriched for autozygosity, which enhances the homozygous occurrence of alleles, including pathogenic alleles in genes that have been associated only with a dominant inheritance pattern. Exome sequencing of patients from consanguineous families with likely recessive phenotypes was performed. In one family, the genotype of the deceased children was inferred from their parents due to lack of available samples. We describe the identification of 11 recessive variants (5 of which are reported here for the first time) in 11 genes for which only dominant disease or risk alleles have been reported. The observed phenotypes for these recessive variants were novel (e.g., FBN2-related myopathy and CSF1R-related brain malformation and osteopetrosis), typical (e.g., ACTG2-related visceral myopathy), or an apparently healthy state (e.g., PDE11A), consistent with the corresponding mouse knockout phenotypes. Our results show that, in the era of genomic sequencing and "reverse phenotyping," recessive variants in dominant genes should not be dismissed based on perceived "incompatibility" with the patient's phenotype before careful consideration.Genet Med advance online publication 06 April 2017.

  13. Mutations in SCAPER cause autosomal recessive retinitis pigmentosa with intellectual disability.

    PubMed

    Tatour, Yasmin; Sanchez-Navarro, Iker; Chervinsky, Elana; Hakonarson, Hakon; Gawi, Haithum; Tahsin-Swafiri, Saoud; Leibu, Rina; Lopez-Molina, Maria Isabel; Fernandez-Sanz, Guillermo; Ayuso, Carmen; Ben-Yosef, Tamar

    2017-08-09

    Retinitis pigmentosa (RP) is the most common form of inherited retinal dystrophy, with a worldwide prevalence of 1 in 4000 persons. While in most cases of RP, the disease is limited to the eye (non-syndromic), over 40 forms of syndromic RP have been described. To identify the genetic basis for syndromic RP in three unrelated families from Israel and Spain. Whole exome sequencing was conducted in one Israeli and two Spanish families segregating autosomal recessive RP with intellectual disability. Complete ophthalmic examination included best-corrected visual acuity, funduscopy, optical coherence tomography, fluorescein angiography, flash visual evoked potentials, and electroretinography. Reverse transcription (RT)-PCR and immunostaining were used to examine the spatial and temporal expression pattern of SCAPER. In all patients, biallelic SCAPER mutations were observed. Clinically, patients with SCAPER mutations show signs of typical RP. In addition, they have mild to moderate intellectual disability and attention-deficit/hyperactivity disorder. SCAPER was found to be ubiquitously expressed in a wide range of human tissues, including retina and brain. Furthermore, RT-PCR analysis revealed that in both mouse eye and brain, Scaper is expressed as early as embryonic day 14. In the mouse retina, SCAPER is located in multiple layers, including the retinal pigment epithelium, photoreceptor outer and inner segments, the inner plexiform layer and the ganglion cell layer. Deleterious SCAPER mutations were identified in four patients from three unrelated families of different ethnic backgrounds, thereby confirming the involvement of this gene in the aetiology of autosomal recessive syndromic RP. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  14. The efficacy of microarray screening for autosomal recessive retinitis pigmentosa in routine clinical practice

    PubMed Central

    van Huet, Ramon A. C.; Pierrache, Laurence H.M.; Meester-Smoor, Magda A.; Klaver, Caroline C.W.; van den Born, L. Ingeborgh; Hoyng, Carel B.; de Wijs, Ilse J.; Collin, Rob W. J.; Hoefsloot, Lies H.

    2015-01-01

    Purpose To determine the efficacy of multiple versions of a commercially available arrayed primer extension (APEX) microarray chip for autosomal recessive retinitis pigmentosa (arRP). Methods We included 250 probands suspected of arRP who were genetically analyzed with the APEX microarray between January 2008 and November 2013. The mode of inheritance had to be autosomal recessive according to the pedigree (including isolated cases). If the microarray identified a heterozygous mutation, we performed Sanger sequencing of exons and exon–intron boundaries of that specific gene. The efficacy of this microarray chip with the additional Sanger sequencing approach was determined by the percentage of patients that received a molecular diagnosis. We also collected data from genetic tests other than the APEX analysis for arRP to provide a detailed description of the molecular diagnoses in our study cohort. Results The APEX microarray chip for arRP identified the molecular diagnosis in 21 (8.5%) of the patients in our cohort. Additional Sanger sequencing yielded a second mutation in 17 patients (6.8%), thereby establishing the molecular diagnosis. In total, 38 patients (15.2%) received a molecular diagnosis after analysis using the microarray and additional Sanger sequencing approach. Further genetic analyses after a negative result of the arRP microarray (n = 107) resulted in a molecular diagnosis of arRP (n = 23), autosomal dominant RP (n = 5), X-linked RP (n = 2), and choroideremia (n = 1). Conclusions The efficacy of the commercially available APEX microarray chips for arRP appears to be low, most likely caused by the limitations of this technique and the genetic and allelic heterogeneity of RP. Diagnostic yields up to 40% have been reported for next-generation sequencing (NGS) techniques that, as expected, thereby outperform targeted APEX analysis. PMID:25999674

  15. The efficacy of microarray screening for autosomal recessive retinitis pigmentosa in routine clinical practice.

    PubMed

    van Huet, Ramon A C; Pierrache, Laurence H M; Meester-Smoor, Magda A; Klaver, Caroline C W; van den Born, L Ingeborgh; Hoyng, Carel B; de Wijs, Ilse J; Collin, Rob W J; Hoefsloot, Lies H; Klevering, B Jeroen

    2015-01-01

    To determine the efficacy of multiple versions of a commercially available arrayed primer extension (APEX) microarray chip for autosomal recessive retinitis pigmentosa (arRP). We included 250 probands suspected of arRP who were genetically analyzed with the APEX microarray between January 2008 and November 2013. The mode of inheritance had to be autosomal recessive according to the pedigree (including isolated cases). If the microarray identified a heterozygous mutation, we performed Sanger sequencing of exons and exon-intron boundaries of that specific gene. The efficacy of this microarray chip with the additional Sanger sequencing approach was determined by the percentage of patients that received a molecular diagnosis. We also collected data from genetic tests other than the APEX analysis for arRP to provide a detailed description of the molecular diagnoses in our study cohort. The APEX microarray chip for arRP identified the molecular diagnosis in 21 (8.5%) of the patients in our cohort. Additional Sanger sequencing yielded a second mutation in 17 patients (6.8%), thereby establishing the molecular diagnosis. In total, 38 patients (15.2%) received a molecular diagnosis after analysis using the microarray and additional Sanger sequencing approach. Further genetic analyses after a negative result of the arRP microarray (n = 107) resulted in a molecular diagnosis of arRP (n = 23), autosomal dominant RP (n = 5), X-linked RP (n = 2), and choroideremia (n = 1). The efficacy of the commercially available APEX microarray chips for arRP appears to be low, most likely caused by the limitations of this technique and the genetic and allelic heterogeneity of RP. Diagnostic yields up to 40% have been reported for next-generation sequencing (NGS) techniques that, as expected, thereby outperform targeted APEX analysis.

  16. Mitochondrial inheritance in yeast.

    PubMed

    Westermann, Benedikt

    2014-07-01

    Mitochondria are the site of oxidative phosphorylation, play a key role in cellular energy metabolism, and are critical for cell survival and proliferation. The propagation of mitochondria during cell division depends on replication and partitioning of mitochondrial DNA, cytoskeleton-dependent mitochondrial transport, intracellular positioning of the organelle, and activities coordinating these processes. Budding yeast Saccharomyces cerevisiae has proven to be a valuable model organism to study the mechanisms that drive segregation of the mitochondrial genome and determine mitochondrial partitioning and behavior in an asymmetrically dividing cell. Here, I review past and recent advances that identified key components and cellular pathways contributing to mitochondrial inheritance in yeast. This article is part of a Special Issue entitled: 18th European Bioenergetic Conference. Guest Editors: Manuela Pereira and Miguel Teixeira.

  17. Autosomal recessive nonsyndromic deafness genes: a review

    PubMed Central

    Duman, Duygu; Tekin, Mustafa

    2013-01-01

    More than 50 percent of prelingual hearing loss is genetic in origin, and of these up to 93 percent are monogenic autosomal recessive traits. Some forms of genetic deafness can be recognized by their associated syndromic features, but in most cases, hearing loss is the only finding and is referred to as nonsyndromic deafness. To date, more than 700 different mutations have been identified in one of 42 genes in individuals with autosomal recessive nonsyndromic hearing loss (ARNSHL). Reported mutations in GJB2, encoding connexin 26, makes this gene the most common cause of hearing loss in many populations. Other relatively common deafness genes include SLC26A4, MYO15A, OTOF, TMC1, CDH23, and TMPRSS3. In this report we summarize genes and mutations reported in families with ARNSHL. Founder effects were demonstrated for some recurrent mutations but the most significant findings are the extreme locus and allelic heterogeneity and different spectrum of genes and mutations in each population. PMID:22652773

  18. Autosomal recessive and dominant polycystic kidney diseases.

    PubMed

    Sessa, A; Righetti, M; Battini, G

    2004-12-01

    It is possible to identify renal cysts in several subjects by ultrasonography imaging techniques. Among the inherited polycystic kidney diseases we include autosomal recessive polycystic kidney disease (ARPKD) and autosomal dominant polycystic diseases such as von Hippel-Lindau disease, tuberous sclerosis complex (TSC1 and TSC2), and autosomal dominant polycystic kidney disease (ADPKD). ARPKD is a rare disease, related to PKHD1 gene, located on chromosome 6p21, that encodes a protein named polyductin/fibrocystin. Pathoanatomical features are bilateral kidney involvement with multiple microcysts, and invariably liver involvement with portal and interlobular fibrosis. A single genetic defect leads to different degrees of renal and hepatic involvement with very different phenotypes and different clinical outcome, in the same family too. ARPKD clinically may show 4 different forms: perinatal, neonatal, infantile, and juvenile. ADPKD is much more frequent (1: 400-1000 live births), and can arise from mutations in 2 different genes, named PKD1 located on chromosome 16p13.3, and PKD2 located on chromosome 4q21-23. The proteins encoded by the PKD1 and PKD2 genes are named polycystins which play crucial roles in several biologic processes. To explain the focal lesions that affected different organs and tissues the "double hit" theory has been proposed (germinal mutation plus somatic mutation on PKD1 or PKD2). Recently, biologic evidence documented the crucial role of the renal primary cilia on the formation of polycystins to induce cystogenesis. ADPKD may be clinically characterized by abdominal pain, hypertension, episodes of gross hematuria, headache, renal stones, aortic and cerebral aneurysms, mitral valve prolapse, and polycystic liver disease. ADPKD is slowly progressive disease responsible for up 10% of end stage renal failure (ESRF) in every country of the world. Male sex, PKD1 gene, episodes of gross hematuria, and the precocity and severity of hypertension play an

  19. Recessive multiple epiphyseal dysplasia (rMED) with homozygosity for C653S mutation in the DTDST gene - Phenotype, molecular diagnosis and surgical treatment of habitual dislocation of multilayered patella: Case report

    PubMed Central

    2010-01-01

    Background Multiple epiphyseal dysplasia (MED) is one of the more common generalised skeletal dysplasias. Due to its clinical heterogeneity diagnosis may be difficult. Mutations of at least six separate genes can cause MED. Joint deformities, joint pain and gait disorders are common symptoms. Case Presentation We report on a 27-year-old male patient suffering from clinical symptoms of autosomal recessive MED with habitual dislocation of a multilayered patella on both sides, on the surgical treatment and on short-term clinical outcome. Clinical findings were: bilateral hip and knee pain, instability of femorotibial and patellofemoral joints with habitual patella dislocation on both sides, contractures of hip, elbow and second metacarpophalangeal joints. Main radiographic findings were: bilateral dislocated multilayered patella, dysplastic medial tibial plateaus, deformity of both femoral heads and osteoarthritis of the hip joints, and deformity of both radial heads. In the molecular genetic analysis, the DTDST mutation g.1984T > A (p.C653S) was found at the homozygote state. Carrier status was confirmed in the DNA of the patient's parents. The mutation could be considered to be the reason for the patient's disease. Surgical treatment of habitual patella dislocation with medialisation of the tibial tuberosity led to an excellent clinical outcome. Conclusions The knowledge of different phenotypes of skeletal dysplasias helps to select genes for genetic analysis. Compared to other DTDST mutations, this is a rather mild phenotype. Molecular diagnosis is important for genetic counselling and for an accurate prognosis. Even in case of a multilayered patella in MED, habitual patella dislocation could be managed successfully by medialisation of the tibial tuberosity. PMID:20525296

  20. Deep Dermatophytosis and Inherited CARD9 Deficiency

    PubMed Central

    Vincent, Quentin B.; Liu, Luyan; Cypowyj, Sophie; Prando, Carolina; Migaud, Mélanie; Taibi, Lynda; Ammar-Khodja, Aomar; Stambouli, Omar Boudghene; Guellil, Boumediene; Jacobs, Frederique; Goffard, Jean-Christophe; Schepers, Kinda; del Marmol, Véronique; Boussofara, Lobna; Denguezli, Mohamed; Larif, Molka; Bachelez, Hervé; Michel, Laurence; Lefranc, Gérard; Hay, Rod; Jouvion, Gregory; Chretien, Fabrice; Fraitag, Sylvie; Bougnoux, Marie-Elisabeth; Boudia, Merad

    2014-01-01

    BACKGROUND Deep dermatophytosis is a severe and sometimes life-threatening fungal infection caused by dermatophytes. It is characterized by extensive dermal and subcutaneous tissue invasion and by frequent dissemination to the lymph nodes and, occasionally, the central nervous system. The condition is different from common superficial dermatophyte infection and has been reported in patients with no known immunodeficiency. Patients are mostly from North African, consanguineous, multiplex families, which strongly suggests a mendelian genetic cause. METHODS We studied the clinical features of deep dermatophytosis in 17 patients with no known immunodeficiency from eight unrelated Tunisian, Algerian, and Moroccan families. Because CARD9 (caspase recruitment domain–containing protein 9) deficiency has been reported in an Iranian family with invasive fungal infections, we also sequenced CARD9 in the patients. RESULTS Four patients died, at 28, 29, 37, and 39 years of age, with clinically active deep dermatophytosis. No other severe infections, fungal or otherwise, were reported in the surviving patients, who ranged in age from 37 to 75 years. The 15 Algerian and Tunisian patients, from seven unrelated families, had a homozygous Q289X CARD9 allele, due to a founder effect. The 2 Moroccan siblings were homozygous for the R101C CARD9 allele. Both alleles are rare deleterious variants. The familial segregation of these alleles was consistent with autosomal recessive inheritance and complete clinical penetrance. CONCLUSIONS All the patients with deep dermatophytosis had autosomal recessive CARD9 deficiency. Deep dermatophytosis appears to be an important clinical manifestation of CARD9 deficiency. (Funded by Agence Nationale pour la Recherche and others.) PMID:24131138

  1. Deep dermatophytosis and inherited CARD9 deficiency.

    PubMed

    Lanternier, Fanny; Pathan, Saad; Vincent, Quentin B; Liu, Luyan; Cypowyj, Sophie; Prando, Carolina; Migaud, Mélanie; Taibi, Lynda; Ammar-Khodja, Aomar; Stambouli, Omar Boudghene; Guellil, Boumediene; Jacobs, Frederique; Goffard, Jean-Christophe; Schepers, Kinda; Del Marmol, Véronique; Boussofara, Lobna; Denguezli, Mohamed; Larif, Molka; Bachelez, Hervé; Michel, Laurence; Lefranc, Gérard; Hay, Rod; Jouvion, Gregory; Chretien, Fabrice; Fraitag, Sylvie; Bougnoux, Marie-Elisabeth; Boudia, Merad; Abel, Laurent; Lortholary, Olivier; Casanova, Jean-Laurent; Picard, Capucine; Grimbacher, Bodo; Puel, Anne

    2013-10-31

    Deep dermatophytosis is a severe and sometimes life-threatening fungal infection caused by dermatophytes. It is characterized by extensive dermal and subcutaneous tissue invasion and by frequent dissemination to the lymph nodes and, occasionally, the central nervous system. The condition is different from common superficial dermatophyte infection and has been reported in patients with no known immunodeficiency. Patients are mostly from North African, consanguineous, multiplex families, which strongly suggests a mendelian genetic cause. We studied the clinical features of deep dermatophytosis in 17 patients with no known immunodeficiency from eight unrelated Tunisian, Algerian, and Moroccan families. Because CARD9 (caspase recruitment domain-containing protein 9) deficiency has been reported in an Iranian family with invasive fungal infections, we also sequenced CARD9 in the patients. Four patients died, at 28, 29, 37, and 39 years of age, with clinically active deep dermatophytosis. No other severe infections, fungal or otherwise, were reported in the surviving patients, who ranged in age from 37 to 75 years. The 15 Algerian and Tunisian patients, from seven unrelated families, had a homozygous Q289X CARD9 allele, due to a founder effect. The 2 Moroccan siblings were homozygous for the R101C CARD9 allele. Both alleles are rare deleterious variants. The familial segregation of these alleles was consistent with autosomal recessive inheritance and complete clinical penetrance. All the patients with deep dermatophytosis had autosomal recessive CARD9 deficiency. Deep dermatophytosis appears to be an important clinical manifestation of CARD9 deficiency. (Funded by Agence Nationale pour la Recherche and others.).

  2. Epigenetic inheritance of proteostasis and ageing

    PubMed Central

    Li, Cheryl; Casanueva, Olivia

    2016-01-01

    Abundant evidence shows that the genome is not as static as once thought and that gene expression can be reversibly modulated by the environment. In some cases, these changes can be transmitted to the next generation even if the environment has reverted. Such transgenerational epigenetic inheritance requires that information be stored in the germline in response to exogenous stressors. One of the most elusive questions in the field of epigenetic inheritance is the identity of such inherited factor(s). Answering this question would allow us to understand how the environment can shape human populations for multiple generations and may help to explain the rapid rise in obesity and neurodegenerative diseases in modern society. It will also provide clues on how we might be able to reprogramme the epigenome to prevent transmission of detrimental phenotypes and identify individuals who might be at increased risk of disease. In this article, we aim to review recent developments in this field, focusing on research conducted mostly in the nematode Caenorhabditis elegans and mice, that link environmental modulators with the transgenerational inheritance of phenotypes that affect protein-folding homoeostasis and ageing. PMID:27744335

  3. Exome sequencing and directed clinical phenotyping diagnose cholesterol ester storage disease presenting as autosomal recessive hypercholesterolemia.

    PubMed

    Stitziel, Nathan O; Fouchier, Sigrid W; Sjouke, Barbara; Peloso, Gina M; Moscoso, Alessa M; Auer, Paul L; Goel, Anuj; Gigante, Bruna; Barnes, Timothy A; Melander, Olle; Orho-Melander, Marju; Duga, Stefano; Sivapalaratnam, Suthesh; Nikpay, Majid; Martinelli, Nicola; Girelli, Domenico; Jackson, Rebecca D; Kooperberg, Charles; Lange, Leslie A; Ardissino, Diego; McPherson, Ruth; Farrall, Martin; Watkins, Hugh; Reilly, Muredach P; Rader, Daniel J; de Faire, Ulf; Schunkert, Heribert; Erdmann, Jeanette; Samani, Nilesh J; Charnas, Lawrence; Altshuler, David; Gabriel, Stacey; Kastelein, John J P; Defesche, Joep C; Nederveen, Aart J; Kathiresan, Sekar; Hovingh, G Kees

    2013-12-01

    Autosomal recessive hypercholesterolemia is a rare inherited disorder, characterized by extremely high total and low-density lipoprotein cholesterol levels, that has been previously linked to mutations in LDLRAP1. We identified a family with autosomal recessive hypercholesterolemia not explained by mutations in LDLRAP1 or other genes known to cause monogenic hypercholesterolemia. The aim of this study was to identify the molecular pathogenesis of autosomal recessive hypercholesterolemia in this family. We used exome sequencing to assess all protein-coding regions of the genome in 3 family members and identified a homozygous exon 8 splice junction mutation (c.894G>A, also known as E8SJM) in LIPA that segregated with the diagnosis of hypercholesterolemia. Because homozygosity for mutations in LIPA is known to cause cholesterol ester storage disease, we performed directed follow-up phenotyping by noninvasively measuring hepatic cholesterol content. We observed abnormal hepatic accumulation of cholesterol in the homozygote individuals, supporting the diagnosis of cholesterol ester storage disease. Given previous suggestions of cardiovascular disease risk in heterozygous LIPA mutation carriers, we genotyped E8SJM in >27 000 individuals and found no association with plasma lipid levels or risk of myocardial infarction, confirming a true recessive mode of inheritance. By integrating observations from Mendelian and population genetics along with directed clinical phenotyping, we diagnosed clinically unapparent cholesterol ester storage disease in the affected individuals from this kindred and addressed an outstanding question about risk of cardiovascular disease in LIPA E8SJM heterozygous carriers.

  4. Dominant inheritance of field-evolved resistance to Bt corn in Busseolafusca.

    PubMed

    Campagne, Pascal; Kruger, Marlene; Pasquet, Rémy; Le Ru, Bruno; Van den Berg, Johnnie

    2013-01-01

    Transgenic crops expressing Bacillus thuringiensis (Bt) toxins have been adopted worldwide, notably in developing countries. In spite of their success in controlling target pests while allowing a substantial reduction of insecticide use, the sustainable control of these pest populations is threatened by the evolution of resistance. The implementation of the "high dose/refuge" strategy for managing insect resistance in transgenic crops aims at delaying the evolution of resistance to Bt crops in pest populations by promoting survival of susceptible insects. However, a crucial condition for the "high dose/refuge" strategy to be efficient is that the inheritance of resistance should be functionally recessive. Busseolafusca developed high levels of resistance to the Bt toxin Cry 1Ab expressed in Bt corn in South Africa. To test whether the inheritance of B. fusca resistance to the Bt toxin could be considered recessive we performed controlled crosses with this pest and evaluated its survival on Bt and non-Bt corn. Results show that resistance of B. fusca to Bt corn is dominant, which refutes the hypothesis of recessive inheritance. Survival on Bt corn was not lower than on non-Bt corn for both resistant larvae and the F1 progeny from resistant × susceptible parents. Hence, resistance management strategies of B. fusca to Bt corn must address non-recessive resistance.

  5. Comparison of the clinical applicability of Miller's classification system to Kumar and Masamatti's classification system of gingival recession

    PubMed Central

    Kumar, Ashish; Gupta, Geeti; Puri, Komal; Bansal, Mansi; Jain, Deept; Khatri, Manish; Masamatti, Sujata Surendra

    2015-01-01

    Background: The aims of the present study were to (i) Find the percentage of recession cases that could be classified by application of Miller's and/or Kumar and Masamatti's classification of gingival recession, and (ii) compare the percentage of clinical applicability of Miller's criteria and Kumar and Masamatti's criteria to the total recessions present. Materials and Methods: A total of 104 patients (1089 recession cases) were included in the study wherein they were classified using both Miller's and Kumar and Masamatti's classification systems of gingival recession. Percentage comparison of the application of both classification systems was done. Results: Data analysis showed that though all the cases of the recession were classified by Kumar and Masamatti's classification, only 34.61% cases were classified by Miller's classification. 19.10% cases were completely (having only labial/buccal recession) classified. In 15.51% (out of 34.61%) cases, only buccal recession was classified according to Miller's criteria and included in this category, although these cases had both buccal and lingual/palatal recessions. Furthermore, 29.75% cases of recession with interdental loss and marginal tissue loss coronal to mucogingival junction (MGJ) remained uncategorized by Miller's classification; categorization of palatal/lingual recession was possible with Kumar and Masamatti's classification. Conclusion: The elaborative evaluation of both buccal and palatal/lingual recession by the Kumar and Masamatti's classification system can be used to overcome the limitations of Miller's classification system, especially the cases with interdental loss and having marginal tissue loss coronal to MGJ. PMID:26644724

  6. Thrombosis in Inherited Fibrinogen Disorders

    PubMed Central

    Korte, Wolfgang; Poon, Man-Chiu; Iorio, Alfonso; Makris, Michael

    2017-01-01

    Although inherited fibrinogen disorders (IFD) are primarily considered to be bleeding disorders, they are associated with a higher thrombotic complication risk than defects in other clotting factors. Managing IFD patients with thrombosis is challenging as anticoagulant treatment may exacerbate the underlying bleeding risk which can be life-threatening. Due to the low prevalence of IFD, there is little information on pathophysiology or optimal treatment of thrombosis in these patients. We searched the literature for cases of thrombosis among IFD patients and identified a total of 128 patient reports. In approximately half of the cases, thromboses were spontaneous, while in the others trauma, surgery, and parturition contributed to the risk. The true mechanism(s) of thrombosis in IFD patients remain to be elucidated. A variety of anticoagulant treatments have been used in the treatment or prevention of thrombosis, sometimes with concurrent fibrinogen replacement therapy. There is no definite evidence that fibrinogen supplementation increases the risk of thrombosis, and it may potentially be effective in the treatment and prevention of both thrombosis and hemorrhage in IFD patients. PMID:28503122

  7. The foundation of extranuclear inheritance: plastid and mitochondrial genetics.

    PubMed

    Hagemann, Rudolf

    2010-03-01

    In 1909 two papers by Correns and by Baur published in volume 1 of Zeitschrift für induktive Abstammungs- und Vererbungslehre (now Molecular Genetics and Genomics) reported on the non-Mendelian inheritance of chlorophyll deficiencies. These papers, reporting the very first cases of extranuclear inheritance, laid the foundation for a new field: non-Mendelian or extranuclear genetics. Correns observed a purely maternal inheritance (in Mirabilis), whereas Baur found a biparental inheritance (in Pelargonium). Correns suspected the non-Mendelian factors in the cytoplasm, while Baur believed that the plastids carry these extranuclear factors. In the following years, Baur's hypothesis was proved to be correct. Baur subsequently developed the theory of plastid inheritance. In many genera the plastids are transmitted only uniparentally by the mother, while in a few genera there is a biparental plastid inheritance. Commonly there is random sorting of plastids during ontogenetic development. Renner and Schwemmle as well as geneticists in other countries added additional details to this theory. Pioneering studies on mitochondrial inheritance in yeast started in 1949 in the group of Ephrussi and Slonimski; respiration-deficient cells (petites in yeast, poky in Neurospora) were demonstrated to be due to mitochondrial mutations. Electron microscopical and biochemical studies (1962-1964) showed that plastids and mitochondria contain organelle-specific DNA molecules. These findings laid the molecular basis for the two branches of extranuclear inheritance: plastid and mitochondrial genetics.

  8. Does gingival recession require surgical treatment?

    PubMed Central

    Chan, Hsun-Liang; Chun, Yong-Hee Patricia; MacEachern, Mark

    2016-01-01

    Gingival recession represents a clinical condition in adults frequently encountered in the general dental practice. It is estimated that 23% of adults in the US have one or more tooth surfaces with ≥ 3 mm gingival recession. Clinicians often time face dilemmas of whether or not to treat such a condition surgically. Therefore, we were charged by the editorial board to answer this critical question: “Does gingival recession require surgical treatment?” An initial condensed literature search was performed using a combination of gingival recession and surgery controlled terms and keywords. An analysis of the search results highlights our limited understanding of the factors that often guide the treatment of gingival recession. Understanding the etiology, prognosis and treatment of gingival recession continues to offer many unanswered questions and challenges in the field of periodontics as we strive to provide the best care possible for our patients. PMID:26427577

  9. Control of the inherited glacial morphology of the post-glacial slope destabilization. The western Romanche valley case study (French western Alps)

    NASA Astrophysics Data System (ADS)

    Schwartz, Stéphane; Zerathe, Swann; Jongmans, Denis; Audin, Laurence; Dumont, Thierry; Carcaillet, Julien

    2017-04-01

    In the main Alpine valleys, the chronological constraints about the onset of the slope movements following glacial retreat are scarse. The western part of the Romanche valley (French western Alps), carved in the micaschists of the Belledonne Massif, is affected by numerous slope destabilizations. A detailed geomorphological study using a high resolution LIDAR digital model elevation coupled with cosmogenic 10Be dating provide a regional view of the dynamics of slope destabilization in this area. Our data show the presence of two contiguous gravitational movements with two distinct kinematics. The Faulaurent landslide, located to the east of the valley, corresponds to a massive slope collapse (volume > 400 hm3) following the total downwastage of the Romanche glacier near 16 ka. In contrast, the Séchilienne landslide (60 hm3), located to the west, shows a progressive and continuous slope destabilization activity since 8 ka. Our dataset coupled with recent sub-surface geophysical investigations allow to propose a new scenario of the post-glacial slope destabilization of valley involving a major control of the inherited glacial morphology.

  10. A novel recessive GUCY2D mutation causing cone-rod dystrophy and not Leber's congenital amaurosis.

    PubMed

    Ugur Iseri, Sibel A; Durlu, Yusuf K; Tolun, Aslihan

    2010-10-01

    Cone-rod dystrophies are inherited retinal dystrophies that are characterized by progressive degeneration of cones and rods, causing an early decrease in central visual acuity and colour vision defects, followed by loss of peripheral vision in adolescence or early adult life. Both genetic and clinical heterogeneity are well known. In a family with autosomal recessive cone-rod dystrophy, genetic analyses comprising genome scan with microsatellite markers, fine mapping and candidate gene approach resulted in the identification of a homozygous missense GUCY2D mutation. This is the first GUCY2D mutation associated with autosomal recessive cone-rod dystrophy rather than Leber's congenital amaurosis (LCA), a severe disease leading to childhood blindness. This study hence establishes GUCY2D, which is a common cause for both recessive LCA and dominant cone-rod dystrophy, as a good candidate for autosomal recessive cone-rod dystrophy.

  11. Telomerase reverse-transcriptase homozygous mutations in autosomal recessive dyskeratosis congenita and Hoyeraal-Hreidarsson syndrome

    PubMed Central

    Marrone, Anna; Walne, Amanda; Tamary, Hannah; Masunari, Yuka; Kirwan, Michael; Beswick, Richard; Vulliamy, Tom; Dokal, Inderjeet

    2010-01-01

    Dyskeratosis congenita (DC) is a multisystem bone marrow failure syndrome characterized by a triad of mucocutaneous abnormalities and an increased predisposition to malignancy. X-linked DC is due to mutations in DKC1, while heterozygous mutations in TERC (telomerase RNA component) and TERT (telomerase reverse transcriptase) have been found in autosomal dominant DC. Many patients with DC remain uncharacterized, particularly families displaying autosomal recessive (AR) inheritance. We have now identified novel homozygous TERT mutations in 2 unrelated consanguineous families, where the index cases presented with classical DC or the more severe variant, Hoyeraal-Hreidarsson (HH) syndrome. These TERT mutations resulted in reduced telomerase activity and extremely short telomeres. As these mutations are homozygous, these patients are predicted to have significantly reduced telomerase activity in vivo. Interestingly, in contrast to patients with heterozygous TERT mutations or hemizygous DKC1 mutations, these 2 homozygous TERT patients were observed to have higher-than-expected TERC levels compared with controls. Collectively, the findings from this study demonstrate that homozygous TERT mutations, resulting in a pure but severe telomerase deficiency, produce a phenotype of classical AR-DC and its severe variant, the HH syndrome. PMID:17785587

  12. Germline recessive mutations in PI4KA are associated with perisylvian polymicrogyria, cerebellar hypoplasia and arthrogryposis.

    PubMed

    Pagnamenta, Alistair T; Howard, Malcolm F; Wisniewski, Eva; Popitsch, Niko; Knight, Samantha J L; Keays, David A; Quaghebeur, Gerardine; Cox, Helen; Cox, Phillip; Balla, Tamas; Taylor, Jenny C; Kini, Usha

    2015-07-01

    Polymicrogyria (PMG) is a structural brain abnormality involving the cerebral cortex that results from impaired neuronal migration and although several genes have been implicated, many cases remain unsolved. In this study, exome sequencing in a family where three fetuses had all been diagnosed with PMG and cerebellar hypoplasia allowed us to identify regions of the genome for which both chromosomes were shared identical-by-descent, reducing the search space for causative variants to 8.6% of the genome. In these regions, the only plausibly pathogenic mutations were compound heterozygous variants in PI4KA, which Sanger sequencing confirmed segregated consistent with autosomal recessive inheritance. The paternally transmitted variant predicted a premature stop mutation (c.2386C>T; p.R796X), whereas the maternally transmitted variant predicted a missense substitution (c.5560G>A; p.D1854N) at a conserved residue within the catalytic domain. Functional studies using expressed wild-type or mutant PI4KA enzyme confirmed the importance of p.D1854 for kinase activity. Our results emphasize the importance of phosphoinositide signalling in early brain development. © The Author 2015. Published by Oxford University Press.

  13. Mitochondrial inheritance in Aspergillus nidulans.

    PubMed

    Coenen, A; Croft, J H; Slakhorst, M; Debets, F; Hoekstra, R

    1996-04-01

    Mitochondrial chloramphenicol and oligomycin resistance mutations were used to investigate mitochondrial inheritance in A. nidulans. Mitochondrial RFLPs could not be used to distinguish between paternal and maternal mitochondria because none were detected in the 54 isolates investigated. Several thousand ascospores from each of 111 hybrid cleistothecia from 21 different crosses between 7 heterokaryon incompatible isolates were tested for biparental inheritance. All mitochondrial inheritance was strictly uniparental. Not one instance of paternal inheritance of mitochondria was observed. The implications of our results for the theory that uniparental inheritance evolved to avoid cytoplasmic conflict are discussed. Possible explanations for the maintenance of strict uniparental inheritance of mitochondria in an inbreeding homothallic organism are suggested. The chloramphenicol resistance marker was inherited preferentially to the oligomycin resistance marker probably due to the inhibited energy production of mitochondria with the oligomycin resistance mutation. The maternal parent was determined for 93 hybrid cleistothecia from 17 crosses between 7 different strains. Contrary to previous reports A. nidulans strains functioned as both maternal and paternal parent in most crosses.

  14. Inherited CARD9 deficiency in 2 unrelated patients with invasive Exophiala infection.

    PubMed

    Lanternier, Fanny; Barbati, Elisa; Meinzer, Ulrich; Liu, Luyan; Pedergnana, Vincent; Migaud, Mélanie; Héritier, Sébastien; Chomton, Maryline; Frémond, Marie-Louise; Gonzales, Emmanuel; Galeotti, Caroline; Romana, Serge; Jacquemin, Emmanuel; Angoulvant, Adela; Bidault, Valeska; Canioni, Danielle; Lachenaud, Julie; Mansouri, Davood; Mahdaviani, Seyed Alireza; Adimi, Parvaneh; Mansouri, Nahal; Jamshidi, Mahin; Bougnoux, Marie-Elisabeth; Abel, Laurent; Lortholary, Olivier; Blanche, Stéphane; Casanova, Jean-Laurent; Picard, Capucine; Puel, Anne

    2015-04-15

    Exophiala species are mostly responsible for skin infections. Invasive Exophiala dermatitidis disease is a rare and frequently fatal infection, with 42 cases reported. About half of these cases had no known risk factors. Similarly, invasive Exophiala spinifera disease is extremely rare, with only 3 cases reported, all in patients with no known immunodeficiency. Autosomal recessive CARD9 deficiency has recently been reported in otherwise healthy patients with severe fungal diseases caused by Candida species, dermatophytes, or Phialophora verrucosa. We investigated an 8-year-old girl from a nonconsanguineous Angolan kindred, who was born in France and developed disseminated E. dermatitidis disease and a 26 year-old woman from an Iranian consaguineous kindred, who was living in Iran and developed disseminated E. spinifera disease. Both patients were otherwise healthy. We sequenced CARD9 and found both patients to be homozygous for loss-of-function mutations (R18W and E323del). The first patient had segmental uniparental disomy of chromosome 9, carrying 2 copies of the maternal CARD9 mutated allele. These are the first 2 patients with inherited CARD9 deficiency and invasive Exophiala disease to be described. CARD9 deficiency should thus be considered in patients with unexplained invasive Exophiala species disease, even in the absence of other infections. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. Inherited CARD9 Deficiency in 2 Unrelated Patients With Invasive Exophiala Infection

    PubMed Central

    Lanternier, Fanny; Barbati, Elisa; Meinzer, Ulrich; Liu, Luyan; Pedergnana, Vincent; Migaud, Mélanie; Héritier, Sébastien; Chomton, Maryline; Frémond, Marie-Louise; Gonzales, Emmanuel; Galeotti, Caroline; Romana, Serge; Jacquemin, Emmanuel; Angoulvant, Adela; Bidault, Valeska; Canioni, Danielle; Lachenaud, Julie; Mansouri, Davood; Mahdaviani, Seyed Alireza; Adimi, Parvaneh; Mansouri, Nahal; Jamshidi, Mahin; Bougnoux, Marie-Elisabeth; Abel, Laurent; Lortholary, Olivier; Blanche, Stéphane; Casanova, Jean-Laurent; Picard, Capucine; Puel, Anne

    2015-01-01

    Background. Exophiala species are mostly responsible for skin infections. Invasive Exophiala dermatitidis disease is a rare and frequently fatal infection, with 42 cases reported. About half of these cases had no known risk factors. Similarly, invasive Exophiala spinifera disease is extremely rare, with only 3 cases reported, all in patients with no known immunodeficiency. Autosomal recessive CARD9 deficiency has recently been reported in otherwise healthy patients with severe fungal diseases caused by Candida species, dermatophytes, or Phialophora verrucosa. Methods. We investigated an 8-year-old girl from a nonconsanguineous Angolan kindred, who was born in France and developed disseminated E. dermatitidis disease and a 26 year-old woman from an Iranian consaguineous kindred, who was living in Iran and developed disseminated E. spinifera disease. Both patients were otherwise healthy. Results. We sequenced CARD9 and found both patients to be homozygous for loss-of-function mutations (R18W and E323del). The first patient had segmental uniparental disomy of chromosome 9, carrying 2 copies of the maternal CARD9 mutated allele. Conclusions. These are the first 2 patients with inherited CARD9 deficiency and invasive Exophiala disease to be described. CARD9 deficiency should thus be considered in patients with unexplained invasive Exophiala species disease, even in the absence of other infections. PMID:25057046

  16. Biochemical characterization of a pedigree with mitochondrially inherited deafness.

    PubMed

    Prezant, R T; Shohat, M; Jaber, L; Pressman, S; Fischel-Ghodsian, N

    1992-11-01

    A large kindred with a predicted 2-locus inheritance of sensorineural deafness, caused by the combination of a mitochondrial and an autosomal recessive mutation, was examined at the biochemical level. Because of the mitochondrial inheritance of this disease, we looked for defects in the oxidative phosphorylation Complexes I, III, IV, and V, the 4 enzymes that include all of the 13 mitochondrially encoded polypeptides. Biosynthetic labelling of lymphoblastoid cells from deaf patients, unaffected siblings, and an unrelated control showed no difference in size, abundance, rate of synthesis, or chloramphenicol-sensitivity of the mitochondrially encoded subunits. Since overall mitochondrial protein synthesis appears normal, these results suggest that the mitochondrial mutation is unlikely to be in a tRNA or rRNA gene. No change in enzymatic levels was seen in lymphoblastoid mitochondria of the deaf patients, compared to unaffected sibs and controls, for Complexes I and IV. Both affected and unaffected family members showed an increase in Complex III activity compared to controls, which may reflect the mitochondrial DNA shared by maternal relatives, or be due to other genetic differences. Complex V activity was increased in deaf individuals compared to their unaffected sibs. Since the family members share the presumptive mitochondrial mutation, differences between deaf and unaffected individuals likely reflect the nuclear background and suggest that the autosomal recessive mutation may be related to the increase in Complex V activity. These biochemical studies provide a guide for sequence analysis of the patients' mitochondrial DNA and for linkage studies in this kindred.

  17. Non-additive phenotypic and transcriptomic inheritance in a citrus allotetraploid somatic hybrid between C. reticulata and C. limon: the case of pulp carotenoid biosynthesis pathway.

    PubMed

    Bassene, Jean Baptiste; Froelicher, Yann; Dhuique-Mayer, Claudie; Mouhaya, Waffa; Ferrer, Rosa Mar; Ancillo, Gema; Morillon, Raphael; Navarro, Luis; Ollitrault, Patrick

    2009-11-01

    Allopolyploidy is known to induce novel patterns of gene expression and often gives rise to new phenotypes. Here we report on the first attempt to relate phenotypic inheritance in an allotetraploid somatic hybrid with gene expression. Carotenoid compounds in the fruit pulp of the two parental species and the hybrid were evaluated quantitatively by HPLC. Only very low levels of beta-carotene and beta-cryptoxanthin were observed in Citrus limon, while beta-cryptoxanthin was a major component of C. reticulata, which also displayed high levels of phytoene, phytofluene, beta-carotene, lutein, zeaxantin and violaxanthin. Total carotenoid content in mandarin juice sacs was 60 times greater than that in lemon. The allotetraploid hybrid produced all the same compounds as mandarin but at very low levels. Transgressive concentration of abscisic acid (ABA) was observed in the somatic hybrid. Real-time RT-PCR of total RNA from juice sacs was used to study expression of seven genes (CitDxs, CitPsy, CitPds, CitZds, CitLcy-b, CitChx-b, and CitZep) of the carotenoid biosynthetic pathway and two genes (CitNced1 and CitNced2) involved in abscisic acid synthesis from carotenoid. Gene expression was significantly higher for mandarin than lemon for seven of the nine genes analyzed. Lemon under expression was partially dominant in the somatic hybrid for three upstream steps of the biosynthetic pathway, particularly for CitDxs. Transgressive over expression was observed for the two CitNced genes. A limitation of the upstream steps of the pathway and a downstream higher consumption of carotenoids may explain the phenotype of the somatic hybrid.

  18. Inheritance of Jurassic rifted margin architecture into the Apennines Neogene mountain building: a case history from the Lucretili Mts. (Latium, Central Italy)

    NASA Astrophysics Data System (ADS)

    Bollati, Andrea; Corrado, Sveva; Marino, Maurizio

    2012-06-01

    The western Lucretili Mts. in the central Apennines (Latium, Italy) have been recently re-mapped in great detail and are the subject of combined stratigraphic, sedimentological and structural investigations. In this paper, we present a new stratigraphic interpretation of the Jurassic paleogeography of western Lucretili Mts., where a rift-derived intrabasinal paleo-high of the Alpine Tethys has been identified for the first time by means of facies analysis and biostratigraphic dating. Recognised facies associations, combined with dated stratigraphic sections, allow to define the morphology of the structural paleo-high and to identify the associated gravity-driven deposits (olistoliths) accumulated in the surrounding basin. Furthermore, we investigated the modes of interaction between Jurassic extensional structures and the subsequent contractional patterns developed during the Tertiary mountain building. In detail, the role played during Apennines tectonics by the paleo-escarpments bounding the paleo-high and by the surrounding olistoliths has been analysed. The paleo-escarpments either acted as focussing features for ENE-directed frontal thrust ramp localisation and were offset with small shortening amounts or reactivated as NNE striking high angle transpressional faults or preserved the original geometries as a result of variable orientation of paleo-escarpments with respect to the Neogene compressive stress field (with ENE oriented sigma1). Newly formed ENE striking tear faults connect these either inherited or neo-formed discontinuities. This complex stratigraphic and structural pattern is substantially different from the previous interpretations of this portion of the central Apennines based on a hypothesised layer-cake stratigraphy deformed by neo-formed Neogene thrusts. This contribution strengthens the importance of integrating facies analyses and structural investigations to detect the influence of pre-orogenic structures on compressive structural patterns

  19. A test of the hypothesis that age at onset in Huntington disease is controlled by an X-linked recessive modifier.

    PubMed Central

    Ridley, R M; Farrer, L A; Frith, C D; Conneally, P M

    1992-01-01

    Data from the Research Roster for Huntington Disease Patients and Families were used to assess the hypothesis that juvenile onset in Huntington disease is determined by an X-linked recessive modifying gene in the affected parent. The observed proportion of affected fathers to affected mothers who had such offspring was not compatible with this hypothesis. Furthermore, neither the excess of affected grandfathers nor the existence of juvenile-onset and adult-onset cases within a sibship would be predicted by this model. We also rejected a more general hypothesis that a major change in gene expression across generations, measured by the presence of juvenile onset and/or major anticipation, is determined by an X-linked modifier. However, the inheritance of a propensity toward juvenile onset via the affected male line could be due to an abnormal pattern of paternal genomic imprinting. PMID:1531730

  20. Internet resources cataloguing inherited disorders in dogs.

    PubMed

    Nicholas, Frank W; Crook, Alice; Sargan, David R

    2011-08-01

    Up-to-date annotated catalogues of known inherited disorders in dogs are freely available on the Internet, providing vital information to existing and prospective dog owners, dog breeders, veterinarians, geneticists and others interested in the occurrence and control of inherited disorders. These resources are the Canine Inherited Disorders Database (CIDD), Inherited Diseases in Dogs (IDID) and Online Mendelian Inheritance in Animals (OMIA) the latter associated with Listing of Inherited Disorders in Animals (LIDA). The history and features of these resources are summarised.

  1. Coalgebraic structure of genetic inheritance.

    PubMed

    Tian, Jianjun; Li, Bai-Lian

    2004-09-01

    Although in the broadly defined genetic algebra, multiplication suggests a forward direction of from parents to progeny, when looking from the reverse direction, it also suggests to us a new algebraic structure-coalge- braic structure, which we call genetic coalgebras. It is not the dual coalgebraic structure and can be used in the construction of phylogenetic trees. Math- ematically, to construct phylogenetic trees means we need to solve equations x([n]) = a, or x([n]) = b. It is generally impossible to solve these equations inalgebras. However, we can solve them in coalgebras in the sense of tracing back for their ancestors. A thorough exploration of coalgebraic structure in genetics is apparently necessary. Here, we develop a theoretical framework of the coalgebraic structure of genetics. From biological viewpoint, we defined various fundamental concepts and examined their elementary properties that contain genetic significance. Mathematically, by genetic coalgebra, we mean any coalgebra that occurs in genetics. They are generally noncoassociative and without counit; and in the case of non-sex-linked inheritance, they are cocommutative. Each coalgebra with genetic realization has a baric property. We have also discussed the methods to construct new genetic coalgebras, including cocommutative duplication, the tensor product, linear combinations and the skew linear map, which allow us to describe complex genetic traits. We also put forward certain theorems that state the relationship between gametic coalgebra and gametic algebra. By Brower's theorem in topology, we prove the existence of equilibrium state for the in-evolution operator.

  2. Recessive mutations in the INS gene result in neonatal diabetes through reduced insulin biosynthesis

    PubMed Central

    Garin, Intza; Edghill, Emma L.; Akerman, Ildem; Rubio-Cabezas, Oscar; Rica, Itxaso; Locke, Jonathan M.; Maestro, Miguel Angel; Alshaikh, Adnan; Bundak, Ruveyde; del Castillo, Gabriel; Deeb, Asma; Deiss, Dorothee; Fernandez, Juan M.; Godbole, Koumudi; Hussain, Khalid; O’Connell, Michele; Klupa, Thomasz; Kolouskova, Stanislava; Mohsin, Fauzia; Perlman, Kusiel; Sumnik, Zdenek; Rial, Jose M.; Ugarte, Estibaliz; Vasanthi, Thiruvengadam; Johnstone, Karen; Flanagan, Sarah E.; Martínez, Rosa; Castaño, Carlos; Patch, Ann-Marie; Fernández-Rebollo, Eduardo; Raile, Klemens; Morgan, Noel; Harries, Lorna W.; Castaño, Luis; Ellard, Sian; Ferrer, Jorge; de Nanclares, Guiomar Perez; Hattersley, Andrew T.

    2010-01-01

    Heterozygous coding mutations in the INS gene that encodes preproinsulin were recently shown to be an important cause of permanent neonatal diabetes. These dominantly acting mutations prevent normal folding of proinsulin, which leads to beta-cell death through endoplasmic reticulum stress and apoptosis. We now report 10 different recessive INS mutations in 15 probands with neonatal diabetes. Functional studies showed that recessive mutations resulted in diabetes because of decreased insulin biosynthesis through distinct mechanisms, including gene deletion, lack of the translation initiation signal, and altered mRNA stability because of the disruption of a polyadenylation signal. A subset of recessive mutations caused abnormal INS transcription, including the deletion of the C1 and E1 cis regulatory elements, or three different single base-pair substitutions in a CC dinucleotide sequence located between E1 and A1 elements. In keeping with an earlier and more severe beta-cell defect, patients with recessive INS mutations had a lower birth weight (−3.2 SD score vs. −2.0 SD score) and were diagnosed earlier (median 1 week vs. 10 weeks) compared to those with dominant INS mutations. Mutations in the insulin gene can therefore result in neonatal diabetes as a result of two contrasting pathogenic mechanisms. Moreover, the recessively inherited mutations provide a genetic demonstration of the essential role of multiple sequence elements that regulate the biosynthesis of insulin in man. PMID:20133622

  3. Characterisation of a large complex intragenic re-arrangement in the FVII gene (F7) avoiding misdiagnosis in inherited factor VII deficiency.

    PubMed

    Giansily-Blaizot, Muriel; Thorel, Delphine; Khau Van Kien, Philippe; Behar, Catherine; Romey, Marie-Catherine; Mugneret, Francine; Schved, Jean-François; Claustres, Mireille

    2007-08-01

    Inherited factor VII (FVII) deficiency is a rare autosomal recessive bleeding disorder mostly caused by point mutations. Large genomic re-arrangements at F7 locus could account for a fraction of mutant alleles that remain unidentified after DNA sequencing, because they escape conventional polymerase chain reaction (PCR)-based techniques. We report the first systematic screening of F7 for large re-arrangements, by semi-quantitative multiplex PCR of fluorescent fragments targeting the 9 exons and the promoter region. A well-characterised cohort of 43 unrelated patients either apparently homozygous for a F7 point mutation or carrying at least one unidentified F7 mutant allele participated in this study. Two large F7 re-arrangements were identified in two FVII-deficient pedigrees, including a discontinuous deletion involving two distinct portions of F7 whose proximal and distal end junctions were characterised. A simple and efficient method for the routine detection of gross alterations of F7, which accounted for 2.3% of mutant alleles in our sample, is now available in inherited FVII deficiency. This test should complement conventional PCR-based techniques not only in unsolved cases, but also where inheritance pattern analysis is not achievable.

  4. “United Pedicle Flap” for management of multiple gingival recessions

    PubMed Central

    Chopra, Aditi; Sivaraman, Karthik; Bhat, Subraya Giliyar

    2016-01-01

    Numerous surgical procedures have evolved and are being modified with time to treat gingival recession by manipulating gingival or mucosal tissues in various ways. However, the decision to choose the most appropriate technique for a given recession site still remains a challenging task for clinicians. Mucogingival deformities such as shallow vestibule, frenal pull, or inadequate attached gingiva complicate the decision and limit the treatment options to an invasive procedure involving soft tissue grafts. The situation is further comprised if there is a nonavailability of adequate donor tissue and patients' unwillingness for procedures involving a second surgical site. In such situations, the recession either remains untreated or has poor treatment outcomes. This case report presents a modified pedicle graft technique for treatment of multiple gingival recessions with shallow vestibule and inadequate attached gingiva. The technique is a promising therapeutic alternative to invasive surgical procedures such as soft tissue grafts for treatment of multiple gingival recessions. PMID:27563212

  5. Nuclear inheritance of erythromycin resistance in human cells: New class of mitochondrial protein synthesis mutants

    SciTech Connect

    Doersen, C.J.; Stanbridge, E.J.

    1982-06-01

    The characterization of two new erythromycin-resistant mutants of HeLa cells is described. The strains ERY2305 and ERY2309 both exhibited resistance to erythromycin in growth assays and cell-free mitochondrial protein synthesis assays. The erythromycin resistance phenotype could not be transferred by cybridization. The mutation appeared to be encoded in the nucleus and inherited as a recessive trait. These two mutants, therefore, represent a new class of erythromycin-resistant mutants in human cells that is distinct from the cytoplasmically inherited mutation in strain ERY2301 described previously.

  6. Genotype-phenotype correlations in recessive RYR1-related myopathies

    PubMed Central

    2013-01-01

    Background RYR1 mutations are typically associated with core myopathies and are the most common overall cause of congenital myopathy. Dominant mutations are most often associated with central core disease and malignant hyperthermia, and genotype-phenotype patterns have emerged from the study of these mutations that have contributed to the understanding of disease pathogenesis. The recent availability of genetic testing for the entire RYR1 coding sequence has led to a dramatic expansion in the identification of recessive mutations in core myopathies and other congenital myopathies. To date, no clear patterns have been identified in these recessive mutations, though no systematic examination has yet been performed. Methods In this study, we investigated genotype-phenotype correlations in a large combined cohort of unpublished (n = 14) and previously reported (n = 92) recessive RYR1 cases. Results Overall examination of this cohort revealed nearly 50% of cases to be non-core myopathy related. Our most significant finding was that hypomorphic mutations (mutations expected to diminish RyR1 expression) were enriched in patients with severe clinical phenotypes. We also determined that hypomorphic mutations were more likely to be encountered in non-central core myopathies. With analysis of the location of non-hypomorphic mutations, we found that missense mutations were generally enriched in the MH/CCD hotspots and specifically enriched in the selectivity filter of the channel pore. Conclusions These results support a hypothesis that loss of protein function is a key predictive disease parameter. In addition, they suggest that decreased RyR1 expression may dictate non-core related pathology though, data on protein expression was limited and should be confirmed in a larger cohort. Lastly, the results implicate abnormal ion conductance through the channel pore in the pathogenesis in recessive core myopathies. Overall, our findings represent a comprehensive analysis of

  7. Strategies for Supporting Recess in Elementary Schools

    ERIC Educational Resources Information Center

    Centers for Disease Control and Prevention, 2014

    2014-01-01

    Recess provides students with a needed break from their structured school day. It can improve children's physical, social, and emotional well-being, and enhance learning. Recess helps children meet the goal of 60 minutes of physical activity (PA) each day, as recommended by the US Department of Health and Human Services. National…

  8. Students with Juvenile Arthritis Participating in Recess

    ERIC Educational Resources Information Center

    Lucas, Matthew D.

    2009-01-01

    The participation of a student with juvenile arthritis in recess can often be both challenging and rewarding for the student and general education teacher. This paper will address common characteristics of students with juvenile arthritis and present basic solutions to improve the education of these students in the recess setting. Initially the…

  9. The Crucial Role of Recess in Schools

    ERIC Educational Resources Information Center

    Ramstetter, Catherine L.; Murray, Robert; Garner, Andrew S.

    2010-01-01

    Background: Recess is at the heart of a vigorous debate over the role of schools in promoting optimal child development and well-being. Reallocating time to accentuate academic concerns is a growing trend and has put recess at risk. Conversely, pressure to increase activity in school has come from efforts to combat childhood obesity. The purpose…

  10. Recess for Elementary School Students. Position Statement

    ERIC Educational Resources Information Center

    National Association for Sport and Physical Education, 2006

    2006-01-01

    It is the position of the National Association for Sport and Physical Education (NASPE) that all elementary school children should be provided with at least one daily period of recess of at least 20 minutes in length. Recess is an essential component of a comprehensive school physical activity program and of the total education experience for…

  11. The Crucial Role of Recess in Schools

    ERIC Educational Resources Information Center

    Ramstetter, Catherine L.; Murray, Robert; Garner, Andrew S.

    2010-01-01

    Background: Recess is at the heart of a vigorous debate over the role of schools in promoting optimal child development and well-being. Reallocating time to accentuate academic concerns is a growing trend and has put recess at risk. Conversely, pressure to increase activity in school has come from efforts to combat childhood obesity. The purpose…

  12. Students with Speech Impairments Participating in Recess

    ERIC Educational Resources Information Center

    Lucas, Matthew D.; Watson, Carolyn R.

    2013-01-01

    The participation of students with speech impairments in recess can often be both challenging and rewarding for the students and teachers. This paper will address common characteristics of students with speech impairments and present basic solutions to improve the experience of these students in the recess setting. Initially the definition,…

  13. Students with Multiple Sclerosis Participating in Recess

    ERIC Educational Resources Information Center

    Lucas, Matthew D.; Brentlinger, Jamie

    2012-01-01

    The participation of a student with Multiple Sclerosis (MS) in recess can often be both challenging and rewarding for the student and teacher. This paper will address common characteristics of students with MS and present basic solutions to improve the experience of these students in the recess setting. Initially, the definition and prevalence of…

  14. Autosomal Recessive Cardiomyopathy Presenting as Acute Myocarditis.

    PubMed

    Belkaya, Serkan; Kontorovich, Amy R; Byun, Minji; Mulero-Navarro, Sonia; Bajolle, Fanny; Cobat, Aurelie; Josowitz, Rebecca; Itan, Yuval; Quint, Raphaelle; Lorenzo, Lazaro; Boucherit, Soraya; Stoven, Cecile; Di Filippo, Sylvie; Abel, Laurent; Zhang, Shen-Ying; Bonnet, Damien; Gelb, Bruce D; Casanova, Jean-Laurent

    2017-04-04

    Myocarditis is inflammation of the heart muscle that can follow various viral infections. Why children only rarely develop life-threatening acute viral myocarditis (AVM), given that the causal viral infections are common, is unknown. Genetic lesions might underlie such susceptibilities. Mouse genetic studies demonstrated that interferon (IFN)-α/β immunity defects increased susceptibility to virus-induced myocarditis. Moreover, variations in human TLR3, a potent inducer of IFNs, were proposed to underlie AVM. This study sought to evaluate the hypothesis that human genetic factors may underlie AVM in previously healthy children. We tested the role of TLR3-IFN immunity using human induced pluripotent stem cell-derived cardiomyocytes. We then performed whole-exome sequencing of 42 unrelated children with acute myocarditis (AM), some with proven viral causes. We found that TLR3- and STAT1-deficient cardiomyocytes were not more susceptible to Coxsackie virus B3 (CVB3) infection than control cells. Moreover, CVB3 did not induce IFN-α/β and IFN-α/β-stimulated genes in control cardiomyocytes. Finally, exogenous IFN-α did not substantially protect cardiomyocytes against CVB3. We did not observe a significant enrichment of rare variations in TLR3- or IFN-α/β-related genes. Surprisingly, we found that homozygous but not heterozygous rare variants in genes associated with inherited cardiomyopathies were significantly enriched in AM-AVM patients compared with healthy individuals (p = 2.22E-03) or patients with other diseases (p = 1.08E-04). Seven of 42 patients (16.7%) carried rare biallelic (homozygous or compound heterozygous) nonsynonymous or splice-site variations in 6 cardiomyopathy-associated genes (BAG3, DSP, PKP2, RYR2, SCN5A, or TNNI3). Previously silent recessive defects of the myocardium may predispose to acute heart failure presenting as AM, notably after common viral infections in children. Copyright © 2017 American College of Cardiology Foundation

  15. The crucial role of recess in school.

    PubMed

    Murray, Robert; Ramstetter, Catherine

    2013-01-01

    Recess is at the heart of a vigorous debate over the role of schools in promoting the optimal development of the whole child. A growing trend toward reallocating time in school to accentuate the more academic subjects has put this important facet of a child's school day at risk. Recess serves as a necessary break from the rigors of concentrated, academic challenges in the classroom. But equally important is the fact that safe and well-supervised recess offers cognitive, social, emotional, and physical benefits that may not be fully appreciated when a decision is made to diminish it. Recess is unique from, and a complement to, physical education--not a substitute for it. The American Academy of Pediatrics believes that recess is a crucial and necessary component of a child's development and, as such, it should not be withheld for punitive or academic reasons.

  16. Reduced bone mineral density and hyaloid vasculature remnants in a consanguineous recessive FEVR family with a mutation in LRP5.

    PubMed

    Downey, L M; Bottomley, H M; Sheridan, E; Ahmed, M; Gilmour, D F; Inglehearn, C F; Reddy, A; Agrawal, A; Bradbury, J; Toomes, C

    2006-09-01

    Familial exudative vitreoretinopathy (FEVR) is an inherited blinding condition characterised by abnormal development of the retinal vasculature. FEVR has multiple modes of inheritance, and homozygous mutations in LRP5 have recently been reported as underlying the recessive form of this disease. The aim of this study was to examine LRP5 in a consanguineous recessive FEVR family and to clarify the eye and bone phenotype associated with recessive FEVR. All family members were examined by slit lamp biomicroscopy and indirect ophthalmoscopy. Linkage to LRP5 was determined by genotyping microsatellite markers, constructing haplotypes and calculating lod scores. Mutation screening of LRP5 was performed by polymerase chain reaction amplification of genomic DNA followed by direct sequencing. Bone mineral density (BMD) was evaluated in all family members using dual energy x ray absorptiometry (DEXA). The clinical features observed in this family were consistent with a diagnosis of recessive FEVR. A homozygous LRP5 missense mutation, G550R, was identified in all affected individuals and all unaffected family members screened were heterozygous carriers of this mutation. Reduced BMD, hyaloid vasculature remnants, and nystagmus were features of the phenotype. Recessive mutations in LRP5 can cause FEVR with reduced BMD and hyaloid vasculature remnants. Assessment of a patient with a provisional diagnosis of FEVR should therefore include investigation of BMD, with reduced levels suggestive of an underlying LRP5 mutation.

  17. Reduced bone mineral density and hyaloid vasculature remnants in a consanguineous recessive FEVR family with a mutation in LRP5

    PubMed Central

    Downey, L M; Bottomley, H M; Sheridan, E; Ahmed, M; Gilmour, D F; Inglehearn, C F; Reddy, A; Agrawal, A; Bradbury, J; Toomes, C

    2006-01-01

    Background/aims Familial exudative vitreoretinopathy (FEVR) is an inherited blinding condition characterised by abnormal development of the retinal vasculature. FEVR has multiple modes of inheritance, and homozygous mutations in LRP5 have recently been reported as underlying the recessive form of this disease. The aim of this study was to examine LRP5 in a consanguineous recessive FEVR family and to clarify the eye and bone phenotype associated with recessive FEVR. Methods All family members were examined by slit lamp biomicroscopy and indirect ophthalmoscopy. Linkage to LRP5 was determined by genotyping microsatellite markers, constructing haplotypes and calculating lod scores. Mutation screening of LRP5 was performed by polymerase chain reaction amplification of genomic DNA followed by direct sequencing. Bone mineral density (BMD) was evaluated in all family members using dual energy x ray absorptiometry (DEXA). Results The clinical features observed in this family were consistent with a diagnosis of recessive FEVR. A homozygous LRP5 missense mutation, G550R, was identified in all affected individuals and all unaffected family members screened were heterozygous carriers of this mutation. Reduced BMD, hyaloid vasculature remnants, and nystagmus were features of the phenotype. Conclusion Recessive mutations in LRP5 can cause FEVR with reduced BMD and hyaloid vasculature remnants. Assessment of a patient with a provisional diagnosis of FEVR should therefore include investigation of BMD, with reduced levels suggestive of an underlying LRP5 mutation. PMID:16929062

  18. Two specific mutations are prevalent causes of recessive retinitis pigmentosa in North American patients of Jewish ancestry.

    PubMed

    Venturini, Giulia; Koskiniemi-Kuendig, Hanna; Harper, Shyana; Berson, Eliot L; Rivolta, Carlo

    2015-04-01

    Retinitis pigmentosa is a Mendelian disease with a very elevated genetic heterogeneity. Most mutations are responsible for less than 1% of cases, making molecular diagnosis a multigene screening procedure. In this study, we assessed whether direct testing of specific alleles could be a valuable screening approach in cases characterized by prevalent founder mutations. We screened 275 North American patients with recessive/isolate retinitis pigmentosa for two mutations: an Alu insertion in the MAK gene and the p.Lys42Glu missense in the DHDDS gene. All patients were unrelated; 35 reported Jewish ancestry and the remainder reported mixed ethnicity. We identified the MAK and DHDDS mutations homozygously in only 2.1% and 0.8%, respectively, of patients of mixed ethnicity, but in 25.7% and 8.6%, respectively, of cases reporting Jewish ancestry. Haplotype analyses revealed that inheritance of the MAK mutation was attributable to a founder effect. In contrast to most mutations associated with retinitis pigmentosa-which are, in general, extremely rare-the two alleles investigated here cause disease in approximately one-third of North American patients reporting Jewish ancestry. Therefore, their screening constitutes an alternative procedure to large-scale tests for patients belonging to this ethnic group, especially in time-sensitive situations.

  19. Inheritance of resistance to yellow mosaic virus in blackgram (Vigna mungo (L.) Hepper).

    PubMed

    Singh, D P

    1980-09-01

    The inheritance of resistance to mungbean yellow mosaic virus (MYMV) was studied in blackgram (Vigna mungo (L.) Hepper). The highly resistant donors Pant U-84 and UPU-2 and a highly susceptible line, UL-2, their F1's, F2's and backcrosses were grown with spreader located every 5 to 6 rows. The resistance was found to be digenic and recessive in all the crosses and free from cytoplasmic effect.

  20. Economic recession and fertility in the developed world.

    PubMed

    Sobotka, Tomáš; Skirbekk, Vegard; Philipov, Dimiter

    2011-01-01

    This article reviews research on the effects of economic recessions on fertility in the developed world. We study how economic downturns, as measured by various indicators, especially by declining GDP levels, falling consumer confidence, and rising unemployment, were found to affect fertility. We also discuss particular mechanisms through which the recession may have influenced fertility behavior, including the effects of economic uncertainty, falling income, changes in the housing market, and rising enrollment in higher education, and also factors that influence fertility indirectly such as declining marriage rates. Most studies find that fertility tends to be pro-cyclical and often rises and declines with the ups and downs of the business cycle. Usually, these aggregate effects are relatively small (typically, a few percentage points) and of short durations; in addition they often influence especially the timing of childbearing and in most cases do not leave an imprint on cohort fertility levels. Therefore, major long-term fertility shifts often continue seemingly uninterrupted during the recession—including the fertility declines before and during the Great Depression of the 1930s and before and during the oil shock crises of the 1970s. Changes in the opportunity costs of childbearing and fertility behavior during economic downturn vary by sex, age, social status, and number of children; childless young adults are usually most affected. Furthermore, various policies and institutions may modify or even reverse the relationship between recessions and fertility. The first evidence pertaining to the recent recession falls in line with these findings. In most countries, the recession has brought a decline in the number of births and fertility rates, often marking a sharp halt to the previous decade of rising fertility rates.

  1. Genetics Home Reference: autosomal recessive axonal neuropathy with neuromyotonia

    MedlinePlus

    ... recessive axonal neuropathy with neuromyotonia autosomal recessive axonal neuropathy with neuromyotonia Enable Javascript to view the expand/ ... Open All Close All Description Autosomal recessive axonal neuropathy with neuromyotonia is a disorder that affects the ...

  2. Inherited peripheral neuropathies due to mitochondrial disorders.

    PubMed

    Cassereau, J; Codron, P; Funalot, B

    2014-05-01

    Mitochondrial disorders (MIDs) are frequently responsible for neuropathies with variable severity. Mitochondrial diseases causing peripheral neuropathies (PNP) may be due to mutations of mitochondrial DNA (mtDNA), as is the case in MERRF and MELAS syndromes, or to mutations of nuclear genes. Secondary abnormalities of mtDNA (such as multiple deletions of muscle mtDNA) may result from mitochondrial disorders due to mutations in nuclear genes involved in mtDNA maintenance. This is the case in several syndromes caused by impaired mtDNA maintenance, such as Sensory Ataxic Neuropathy, Dysarthria and Ophthalmoplegia (SANDO) due to recessive mutations in the POLG gene, which encodes the catalytic subunit of mtDNA polymerase (DNA polymerase gamma), or Mitochondrial Neuro-Gastro-Intestinal Encephalomyopathy (MNGIE), due to recessive mutations in the TYMP gene, which encodes thymidine phosphorylase. The last years have seen a growing list of evidence demonstrating that mitochondrial bioenergetics and dynamics might be dysfunctional in axonal Charcot-Marie-Tooth disease (CMT2), and these mechanisms might present a common link between dissimilar CMT2-causing genes. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  3. Inherited pancreatic cancer syndromes.

    PubMed

    Solomon, Sheila; Das, Siddhartha; Brand, Randall; Whitcomb, David C

    2012-01-01

    Pancreatic cancer remains one of the most challenging of all cancers. Genetic risk factors are believed to play a major role, but other than genes coding for blood group, genetic risks for sporadic cases remain elusive. However, several germline mutations have been identified that lead to hereditary pancreatic cancer, familial pancreatic cancer, and increased risk for pancreatic cancer as part of a familial cancer syndrome. The most important genes with variants increasing risk for pancreatic cancer include BRCA1, BRCA2, PALB2, ATM, CDKN2A, APC, MLH1, MSH2, MSH6, PMS2, PRSS1, and STK11. Recognition of members of high-risk families is important for understanding pancreatic cancer biology, for recommending risk reduction strategies and, in some cases, initiating cancer surveillance programs. Because the best methods for surveillance have not been established, the recommendation to refer at-risk patients to centers with ongoing research programs in pancreatic cancer surveillance is supported.

  4. Interdisciplinary psychosocial care for families with inherited cardiovascular diseases.

    PubMed

    Caleshu, Colleen; Kasparian, Nadine A; Edwards, Katharine S; Yeates, Laura; Semsarian, Christopher; Perez, Marco; Ashley, Euan; Turner, Christian J; Knowles, Joshua W; Ingles, Jodie

    2016-10-01

    Inherited cardiovascular diseases pose unique and complex psychosocial challenges for families, including coming to terms with life-long cardiac disease, risk of sudden death, grief related to the sudden death of a loved one, activity restrictions, and inheritance risk to other family members. Psychosocial factors impact not only mental health but also physical health and cooperation with clinical recommendations. We describe an interdisciplinary approach to the care of families with inherited cardiovascular disease, in which psychological care provided by specialized cardiac genetic counselors, nurses, and psychologists is embedded within the cardiovascular care team. We report illustrative cases and the supporting literature to demonstrate common scenarios, as well as practical guidance for clinicians working in the inherited cardiovascular disease setting.

  5. Compositional inheritance: comparison of self-assembly and catalysis.

    PubMed

    Wu, Meng; Higgs, Paul G

    2008-10-01

    Genetic inheritance in modern cells is due to template-directed replication of nucleic acids. However, the difficulty of prebiotic synthesis of long information-carrying polymers like RNA raises the question of whether some other form of heredity is possible without polymers. As an alternative, the lipid world theory has been proposed, which considers non-covalent assemblies of lipids, such as micelles and vesicles. Assemblies store information in the form of a non-random molecular composition, and this information is passed on when the assemblies divide, i.e. the assemblies show compositional inheritance. Here, we vary several important assumptions of previous lipid world models and show that compositional inheritance is relevant more generally than the context in which it was originally proposed. Our models assume that interaction occurs between nearest neighbour molecules only, and account for spatial segregation of molecules of different types within the assembly. We also draw a distinction between a self-assembly model, in which the composition is determined by mutually favourable interaction energies between the molecules, and a catalytic model, in which the composition is determined by mutually favourable catalysis. We show that compositional inheritance occurs in both models, although the self-assembly case seems more relevant if the molecules are simple lipids. In the case where the assemblies are composed of just two types of molecules, there is a strong analogy with the classic two-allele Moran model from population genetics. This highlights the parallel between compositional inheritance and genetic inheritance.

  6. Compositional Inheritance: Comparison of Self-assembly and Catalysis

    NASA Astrophysics Data System (ADS)

    Wu, Meng; Higgs, Paul G.

    2008-10-01

    Genetic inheritance in modern cells is due to template-directed replication of nucleic acids. However, the difficulty of prebiotic synthesis of long information-carrying polymers like RNA raises the question of whether some other form of heredity is possible without polymers. As an alternative, the lipid world theory has been proposed, which considers non-covalent assemblies of lipids, such as micelles and vesicles. Assemblies store information in the form of a non-random molecular composition, and this information is passed on when the assemblies divide, i.e . the assemblies show compositional inheritance. Here, we vary several important assumptions of previous lipid world models and show that compositional inheritance is relevant more generally than the context in which it was originally proposed. Our models assume that interaction occurs between nearest neighbour molecules only, and account for spatial segregation of molecules of different types within the assembly. We also draw a distinction between a self-assembly model, in which the composition is determined by mutually favourable interaction energies between the molecules, and a catalytic model, in which the composition is determined by mutually favourable catalysis. We show that compositional inheritance occurs in both models, although the self-assembly case seems more relevant if the molecules are simple lipids. In the case where the assemblies are composed of just two types of molecules, there is a strong analogy with the classic two-allele Moran model from population genetics. This highlights the parallel between compositional inheritance and genetic inheritance.

  7. Homozygous/Compound Heterozygous Triadin Mutations Associated With Autosomal-Recessive Long-QT Syndrome and Pediatric Sudden Cardiac Arrest: Elucidation of the Triadin Knockout Syndrome.

    PubMed

    Altmann, Helene M; Tester, David J; Will, Melissa L; Middha, Sumit; Evans, Jared M; Eckloff, Bruce W; Ackerman, Michael J

    2015-06-09

    Long-QT syndrome (LQTS) may result in syncope, seizures, or sudden cardiac arrest. Although 16 LQTS-susceptibility genes have been discovered, 20% to 25% of LQTS remains genetically elusive. We performed whole-exome sequencing child-parent trio analysis followed by recessive and sporadic inheritance modeling and disease-network candidate analysis gene ranking to identify a novel underlying genetic mechanism for LQTS. Subsequent mutational analysis of the candidate gene was performed with polymerase chain reaction, denaturing high-performance liquid chromatography, and DNA sequencing on a cohort of 33 additional unrelated patients with genetically elusive LQTS. After whole-exome sequencing and variant filtration, a homozygous p.D18fs*13 TRDN-encoded triadin frameshift mutation was discovered in a 10-year-old female patient with LQTS with a QTc of 500 milliseconds who experienced recurrent exertion-induced syncope/cardiac arrest beginning at 1 year of age. Subsequent mutational analysis of TRDN revealed either homozygous or compound heterozygous frameshift mutations in 4 of 33 unrelated cases of LQTS (12%). All 5 TRDN-null patients displayed extensive T-wave inversions in precordial leads V1 through V4, with either persistent or transient QT prolongation and severe disease expression of exercise-induced cardiac arrest in early childhood (≤3 years of age) and required aggressive therapy. The overall yield of TRDN mutations was significantly greater in patients ≤10 years of age (5 of 10, 50%) compared with older patients (0 of 24, 0%; P=0.0009). We identified TRDN as a novel underlying genetic basis for recessively inherited LQTS. All TRDN-null patients had strikingly similar phenotypes. Given the recurrent nature of potential lethal arrhythmias, patients fitting this phenotypic profile should undergo cardiac TRDN genetic testing. © 2015 American Heart Association, Inc.

  8. Kin selection under blending inheritance.

    PubMed

    Gardner, Andy

    2011-09-07

    Why did Darwin fail to develop his insights on kin selection into a proper theory of social adaptation? One suggestion has been that his inadequate understanding of heredity kept the problem out of focus. Here, I determine whether it is possible to develop a quantitative theory of kin selection upon the assumption of blending inheritance. I find that, whilst Hamilton's rule of kin selection can be readily derived under the assumption of blending inheritance, this mechanism complicates the computation of relatedness coefficients, and can even cause them to fluctuate over generations. Nevertheless, I show that the ultimate criterion for selection to favour any social trait - i.e. a time-average of Hamilton's rule - remains the same as under particulate inheritance. By eliminating the gene from the theory of kin selection, I clarify the role that it plays in the theory of social adaptation.

  9. Imitation as an inheritance system

    PubMed Central

    Shea, Nicholas

    2009-01-01

    What is the evolutionary significance of the various mechanisms of imitation, emulation and social learning found in humans and other animals? This paper presents an advance in the theoretical resources for addressing that question, in the light of which standard approaches from the cultural evolution literature should be refocused. The central question is whether humans have an imitation-based inheritance system—a mechanism that has the evolutionary function of transmitting behavioural phenotypes reliably down the generations. To have the evolutionary power of an inheritance system, an imitiation-based mechanism must meet a range of demanding requirements. The paper goes on to review the evidence for and against the hypothesis that there is indeed an imitation-based inheritance system in humans. PMID:19620113

  10. PGD for inherited cardiac diseases.

    PubMed

    Kuliev, Anver; Pomerantseva, Ekaterina; Polling, Dana; Verlinsky, Oleg; Rechitsky, Svetlana

    2012-04-01

    Preimplantation genetic diagnosis (PGD) has been applied for more than 200 different inherited conditions, with expanding application to common disorders with genetic predisposition. One of the recent indications for PGD has been inherited cardiac disease, for which no preclinical diagnosis and preventive management may exist and which may lead to premature or sudden death. This paper presents the first, as far as is known, cumulative experience of PGD for inherited cardiac diseases, including familial hypertrophic and dilated cardiomyopathy, cardioencephalomyopathy and Emery-Dreifuss muscular dystrophy. A total of 18 PGD cycles were performed, resulting in transfer in 15 of them, which yielded nine unaffected pregnancies and the births of seven disease- or disease predisposition-free children. The data open the prospect of PGD for inherited cardiac diseases, allowing couples carrying cardiac disease predisposing genes to reproduce without much fear of having offspring with these genes, which are at risk for premature or sudden death. Preimplantation genetic diagnosis (PGD) is currently an established clinical procedure in assisted reproduction and genetic practices. Its application has been expanding beyond traditional indications of prenatal diagnosis and currently includes common disorders with genetic predisposition, such as inherited forms of cancer. This applies also to the diseases with no current prospect of treatment, which may manifest despite presymptomatic diagnosis and follow up, when PGD may provide the only relief for the at-risk couples to reproduce. One of the recent indications for PGD has been inherited cardiac disease, for which no preclinical diagnosis and preventive management may exist and which may lead to premature or sudden death. We present here our first cumulative experience of PGD for inherited cardiac diseases, including familial hypertrophic and dilated cardiomyopathy, cardioencephalomyopathy and Emery-Dreifuss muscular dystrophy. A

  11. Characterization of an Early-Onset, Autosomal Recessive, Progressive Retinal Degeneration in Bengal Cats

    PubMed Central

    Ofri, Ron; Reilly, Christopher M.; Maggs, David J.; Fitzgerald, Paul G.; Shilo-Benjamini, Yael; Good, Kathryn L.; Grahn, Robert A.; Splawski, Danielle D.; Lyons, Leslie A.

    2015-01-01

    Purpose A form of retinal degeneration suspected to be hereditary was discovered in a family of Bengal cats. A breeding colony was established to characterize disease progression clinically, electrophysiologically, and morphologically, and to investigate the mode of inheritance. Methods Affected and related cats were donated by owners for breeding trials and pedigree analysis. Kittens from test and complementation breedings underwent ophthalmic and neuro-ophthalmic examinations and ERG, and globes were evaluated using light microscopy. Results Pedigree analysis, along with test and complementation breedings, indicated autosomal recessive inheritance and suggested that this disease is nonallelic to a retinal degeneration found in Persian cats. Mutation analysis confirmed the disease is not caused by CEP290 or CRX variants found predominantly in Abyssinian and Siamese cats. Ophthalmoscopic signs of retinal degeneration were noted at 9 weeks of age and became more noticeable over the next 4 months. Visual deficits were behaviorally evident by 1 year of age. Electroretinogram demonstrated reduced rod and cone function at 7 and 9 weeks of age, respectively. Rod responses were mostly extinguished at 14 weeks of age; cone responses were minimal by 26 weeks. Histologic degeneration was first observed at 8 weeks, evidenced by reduced photoreceptor numbers, then rapid deterioration of the photoreceptor layer and, subsequently, severe outer retinal degeneration. Conclusions A recessively inherited primary photoreceptor degeneration was characterized in the Bengal cat. The disease is characterized by early onset, with histologic, ophthalmoscopic, and electrophysiological signs evident by 2 months of age, and rapid progression to blindness. PMID:26258614

  12. A heterozygous 21-bp deletion in CAPN3 causes dominantly inherited limb girdle muscular dystrophy.

    PubMed

    Vissing, John; Barresi, Rita; Witting, Nanna; Van Ghelue, Marijke; Gammelgaard, Lise; Bindoff, Laurence A; Straub, Volker; Lochmüller, Hanns; Hudson, Judith; Wahl, Christoph M; Arnardottir, Snjolaug; Dahlbom, Kathe; Jonsrud, Christoffer; Duno, Morten

    2016-08-01

    Limb girdle muscular dystrophy type 2A is the most common limb girdle muscular dystrophy form worldwide. Although strict recessive inheritance is assumed, patients carrying a single mutation in the calpain 3 gene (CAPN3) are reported. Such findings are commonly attributed to incomplete mutation screening. In this investigation, we report 37 individuals (age range: 21-85 years, 21 females and 16 males) from 10 families in whom only one mutation in CAPN3 could be identified; a 21-bp, in-frame deletion (c.643_663del21). This mutation co-segregated with evidence of muscle disease and autosomal dominant transmission in several generations. Evidence of muscle disease was indicated by muscle pain, muscle weakness and wasting, significant fat replacement of muscles on imaging, myopathic changes on muscle biopsy and loss of calpain 3 protein on western blotting. Thirty-one of 34 patients had elevated creatine kinase or myoglobin. Muscle weakness was generally milder than observed in limb girdle muscular dystrophy type 2A, but affected the same muscle groups (proximal leg, lumbar paraspinal and medial gastrocnemius muscles). In some cases, the weakness was severely disabling. The 21-bp deletion did not affect mRNA maturation. Calpain 3 expression in muscle, assessed by western blot, was below 15% of normal levels in the nine mutation carriers in whom this could be tested. Haplotype analysis in four families from three different countries suggests that the 21-bp deletion is a founder mutation. This study provides strong evidence that heterozygosity for the c.643_663del21 deletion in CAPN3 results in a dominantly inherited muscle disease. The normal expression of mutated mRNA and the severe loss of calpain 3 on western blotting, suggest a dominant negative effect with a loss-of-function mechanism affecting the calpain 3 homodimer. This renders patients deficient in calpain 3 as in limb girdle muscular dystrophy type 2A, albeit in a milder form in most cases. Based on findings

  13. Prominent Optic Disc Featured in Inherited Retinopathy.

    PubMed

    Todorova, M G; Bojinova, R I; Valmaggia, C; Schorderet, D F

    2017-02-01

    Background We investigated the relationship between prominent optic disc (POD) and inherited retinal dystrophy (IRD). Patients and Methods A cross-sectional consecutive study was performed in 10 children and 11 adults of 7 non-related families. We performed clinical phenotyping, including a detailed examination, fundus autofluorescence, and colour fundus and OCT imaging. Genetic testing was subsequently performed for all family members presenting retinal pathology. Results In 4 members of a 3-generation family, hyperfluorescent deposits on the surface of POD were related to a p.(L224M) heterozygous mutation in BEST1. In the second family, one member presented deposits located on the surface on hyperaemic OD and a compound p.(R141H);(A195V) mutation in BEST1. In the third family, POD was observed in father and child with early onset cone-rod dystrophy and a novel autosomal recessive p.(W31*) homozygous mutation in ABCA4. In the fourth family, POD with "mulberry-like" deposits and attenuated vessels were observed in a 7-year old girl, with a mutation in USH1A, and with early onset rod-cone dystrophy, associated with hearing loss. In the fifth family, blurry OD with tortuous vessels was observed in 4 consanguineous female carriers and a hemizygous boy with a p.(R200H) mutation in the X-linked retinoschisis RS1. In the sixth family, a mother and her son were both affected with POD and attenuated peripapillary vessels, and presented with a p.(Y836C) heterozygous mutation in TOPORS, thus confirming autosomal dominant RP. In the seventh family, in 3 family members with POD, compound p.(L541P;A1038 V);(G1961E) mutations in ABCA4 confirmed the diagnosis of Stargardt disease. Conclusions A variety of OD findings are found in a genetically heterogeneous group of IRDs. In the presence of POD, an inherited progressive photoreceptor disease should be ruled out.

  14. [Contribution to the inheritance of schizophrenic psychosis].

    PubMed

    Feyler, K P

    2000-05-01

    This case presentation involves a family study looking at the inheritance of schizophrenic psychosis. It refers to the increasing risk of disease in correlation to the closeness of the relationship. The study includes both affected parents, their three children and one grandchild, all of whom had multiple hospital admissions and received psychiatric treatment. The clinical features were typical of schizophrenia. The severity of illness increased within the later generation. This study indicates a high risk correlation in this family and is in keeping with other current field studies.

  15. Have Employment Patterns in Recessions Changed?.

    ERIC Educational Resources Information Center

    Bowers, Norman

    1981-01-01

    A survey of postwar recessions shows that the increasing proportion of service sector jobs has moderated overall employment declines and that women in nontraditional jobs, Blacks, and youths bear a disproportionate share of job losses. (LRA)

  16. Genetics Home Reference: autosomal recessive congenital methemoglobinemia

    MedlinePlus

    ... it alters a molecule within these cells called hemoglobin . Hemoglobin carries oxygen to cells and tissues throughout the ... autosomal recessive congenital methemoglobinemia , some of the normal hemoglobin is replaced by an abnormal form called methemoglobin, ...

  17. Graduated recession of the superior oblique muscle.

    PubMed Central

    Caldeira, J A

    1975-01-01

    Recession of the superior oblique was performed bilaterally in 12 patients with the A phenomenon and unilaterally in four patients with vertical imbalance. The results are discussed. Images PMID:1191613

  18. Systematic review of suicide in economic recession

    PubMed Central

    Oyesanya, Mayowa; Lopez-Morinigo, Javier; Dutta, Rina

    2015-01-01

    AIM: To provide a systematic update of the evidence concerning the relationship between economic recession and suicide. METHODS: A keyword search of Ovid Medline, Embase, Embase Classic, PsycINFO and PsycARTICLES was performed to identify studies that had investigated the association between economic recession and suicide. RESULTS: Thirty-eight studies met predetermined selection criteria and 31 of them found a positive association between economic recession and increased suicide rates. Two studies reported a negative association, two articles failed to find such an association, and three studies were inconclusive. CONCLUSION: Economic recession periods appear to increase overall suicide rates, although further research is warranted in this area, particularly in low income countries. PMID:26110126

  19. Genetics Home Reference: autosomal recessive hypotrichosis

    MedlinePlus

    ... erythema), itchiness (pruritus), or missing patches of skin (erosions) on the scalp. In areas of poor hair ... recessive hypotrichosis with monilethrix hairs and congenital scalp erosions. J Invest Dermatol. 2006 Jun;126(6):1286- ...

  20. Have Employment Patterns in Recessions Changed?.

    ERIC Educational Resources Information Center

    Bowers, Norman

    1981-01-01

    A survey of postwar recessions shows that the increasing proportion of service sector jobs has moderated overall employment declines and that women in nontraditional jobs, Blacks, and youths bear a disproportionate share of job losses. (LRA)

  1. Hospital Capital Investment During the Great Recession.

    PubMed

    Choi, Sung

    2017-01-01

    Hospital capital investment is important for acquiring and maintaining technology and equipment needed to provide health care. Reduction in capital investment by a hospital has negative implications for patient outcomes. Most hospitals rely on debt and internal cash flow to fund capital investment. The great recession may have made it difficult for hospitals to borrow, thus reducing their capital investment. I investigated the impact of the great recession on capital investment made by California hospitals. Modeling how hospital capital investment may have been liquidity constrained during the recession is a novel contribution to the literature. I estimated the model with California Office of Statewide Health Planning and Development data and system generalized method of moments. Findings suggest that not-for-profit and public hospitals were liquidity constrained during the recession. Comparing the changes in hospital capital investment between 2006 and 2009 showed that hospitals used cash flow to increase capital investment by $2.45 million, other things equal.

  2. Hyaline Fibromatosis Syndrome: A Rare Inherited Disorder

    PubMed Central

    Mantri, Meeta Dipak; Pradeep, Mahajan M; Kalpesh, Patil O; Pranavsinh, Raj J

    2016-01-01

    Hyaline fibromatosis syndrome (HFS) is rare autosomal recessive disease characterized by the deposition of amorphous hyaline material in skin and visceral organs. It represents a disease spectrum with infantile systemic hyalinosis (ISH) being the severe form and juvenile hyaline fibromatosis (JHF) being the mild form. Dermatologic manifestations include thickened skin, perianal nodules, and facial papules, gingival hyperplasia, large subcutaneous tumors on the scalp, hyperpigmented plaques over the metacarpophalangeal joints and malleoli, and joint contractures. ISH shows a severe visceral involvement, recurrent infections, and early death. We report a case of 2.5-year-old female patient who presented with HFS who had overlapping features of both ISH and JHF. To the best of our knowledge, very few cases of HFS have been reported in Indian literature till date. PMID:27688461

  3. [Asphyxiating thoracic dysplasia (Jeune syndrome): about two cases].

    PubMed

    Harou, K; L'Hermite, M

    2010-04-01

    Asphyxiating thoracic dysplasia (Jeune syndrome) is an osteochondrodysplasia with autosomal recessive inheritance, characterised by a nanism with rhizomelic predominance, associated with a narrow thorax. It induces an alteration of the respiratory function that conditions the prognosis, which is worsened in case of associated visceral lesions (probably related to mutations of genes implicated in ciliary development, as recently described). We report the observation of two severe cases of Jeune syndrome to emphasize the advancement of imaging, especially echography, and molecular biology in establishing prenatal diagnosis as well as prognosis of this syndrome. (c) 2009 Elsevier Masson SAS. All rights reserved.

  4. Serous retinal detachment after trabeculectomy in angle recession glaucoma.

    PubMed

    Roy, Avik Kumar; Padhy, Debananda

    2015-01-01

    An 18-year-old male with 360 degree angle recession after blunt trauma in his right eye developed uncontrolled intraocular pressure (IOP) despite four antiglaucoma medications (AGM) with advancing disc damage. He underwent trabeculectomy with intraoperative mitomycin-c (MMC) application. There was an intraoperative vitreous prolapse which was managed accordingly. On post-surgery day 1, he had shallow choroidal detachment superiorly with non-recordable IOP. This was deteriorated 1 week postoperatively as choroidal detachment proceeded to serous retinal detachment. He was started with systemic steroid in addition to topical route. The serous effusions subsided within 2 weeks time. At the last follow up at 3 months, he was enjoying good visual acuity, deep anterior chamber, diffuse bleb, an IOP in low teens off any AGM and attached retina. This case highlights the rare occurrence of serous retinal detachment after surgical management of angle recession glaucoma.

  5. Whole exome sequencing using Ion Proton system enables reliable genetic diagnosis of inherited retinal dystrophies.

    PubMed

    Riera, Marina; Navarro, Rafael; Ruiz-Nogales, Sheila; Méndez, Pilar; Burés-Jelstrup, Anniken; Corcóstegui, Borja; Pomares, Esther

    2017-02-09

    Inherited retinal dystrophies (IRD) comprise a wide group of clinically and genetically complex diseases that progressively affect the retina. Over recent years, the development of next-generation sequencing (NGS) methods has transformed our ability to diagnose heterogeneous diseases. In this work, we have evaluated the implementation of whole exome sequencing (WES) for the molecular diagnosis of IRD. Using Ion Proton(TM) system, we simultaneously analyzed 212 genes that are responsible for more than 25 syndromic and non-syndromic IRD. This approach was used to evaluate 59 unrelated families, with the pathogenic variant(s) successfully identified in 71.18% of cases. Interestingly, the mutation detection rate varied substantially depending on the IRD subtype. Overall, we found 63 different mutations (21 novel) in 29 distinct genes, and performed in vivo functional studies to determine the deleterious impact of variants identified in MERTK, CDH23, and RPGRIP1. In addition, we provide evidences that support CDHR1 as a gene responsible for autosomal recessive retinitis pigmentosa with early macular affectation, and present data regarding the disease mechanism of this gene. Altogether, these results demonstrate that targeted WES of all IRD genes is a reliable, hypothesis-free approach, and a cost- and time-effective strategy for the routine genetic diagnosis of retinal dystrophies.

  6. Whole exome sequencing using Ion Proton system enables reliable genetic diagnosis of inherited retinal dystrophies

    PubMed Central

    Riera, Marina; Navarro, Rafael; Ruiz-Nogales, Sheila; Méndez, Pilar; Burés-Jelstrup, Anniken; Corcóstegui, Borja; Pomares, Esther

    2017-01-01

    Inherited retinal dystrophies (IRD) comprise a wide group of clinically and genetically complex diseases that progressively affect the retina. Over recent years, the development of next-generation sequencing (NGS) methods has transformed our ability to diagnose heterogeneous diseases. In this work, we have evaluated the implementation of whole exome sequencing (WES) for the molecular diagnosis of IRD. Using Ion ProtonTM system, we simultaneously analyzed 212 genes that are responsible for more than 25 syndromic and non-syndromic IRD. This approach was used to evaluate 59 unrelated families, with the pathogenic variant(s) successfully identified in 71.18% of cases. Interestingly, the mutation detection rate varied substantially depending on the IRD subtype. Overall, we found 63 different mutations (21 novel) in 29 distinct genes, and performed in vivo functional studies to determine the deleterious impact of variants identified in MERTK, CDH23, and RPGRIP1. In addition, we provide evidences that support CDHR1 as a gene responsible for autosomal recessive retinitis pigmentosa with early macular affectation, and present data regarding the disease mechanism of this gene. Altogether, these results demonstrate that targeted WES of all IRD genes is a reliable, hypothesis-free approach, and a cost- and time-effective strategy for the routine genetic diagnosis of retinal dystrophies. PMID:28181551

  7. HYDRORECESSION: A toolbox for streamflow recession analysis

    NASA Astrophysics Data System (ADS)

    Arciniega, S.

    2015-12-01

    Streamflow recession curves are hydrological signatures allowing to study the relationship between groundwater storage and baseflow and/or low flows at the catchment scale. Recent studies have showed that streamflow recession analysis can be quite sensitive to the combination of different models, extraction techniques and parameter estimation methods. In order to better characterize streamflow recession curves, new methodologies combining multiple approaches have been recommended. The HYDRORECESSION toolbox, presented here, is a Matlab graphical user interface developed to analyse streamflow recession time series with the support of different tools allowing to parameterize linear and nonlinear storage-outflow relationships through four of the most useful recession models (Maillet, Boussinesq, Coutagne and Wittenberg). The toolbox includes four parameter-fitting techniques (linear regression, lower envelope, data binning and mean squared error) and three different methods to extract hydrograph recessions segments (Vogel, Brutsaert and Aksoy). In addition, the toolbox has a module that separates the baseflow component from the observed hydrograph using the inverse reservoir algorithm. Potential applications provided by HYDRORECESSION include model parameter analysis, hydrological regionalization and classification, baseflow index estimates, catchment-scale recharge and low-flows modelling, among others. HYDRORECESSION is freely available for non-commercial and academic purposes.

  8. Genetics of inherited cardiomyopathy.

    PubMed

    Jacoby, Daniel; McKenna, William J

    2012-02-01

    During the past two decades, numerous disease-causing genes for different cardiomyopathies have been identified. These discoveries have led to better understanding of disease pathogenesis and initial steps in the application of mutation analysis in the evaluation of affected individuals and their family members. As knowledge of the genetic abnormalities, and insight into cellular and organ biology has grown, so has appreciation of the level of complexity of interaction between genotype and phenotype across disease states. What were initially thought to be one-to-one gene-disease correlates have turned out to display important relational plasticity dependent in large part on the genetic and environmental backgrounds into which the genes of interest express. The current state of knowledge with regard to genetics of cardiomyopathy represents a starting point to address the biology of disease, but is not yet developed sufficiently to supplant clinically based classification systems or, in most cases, to guide therapy to any significant extent. Future work will of necessity be directed towards elucidation of the biological mechanisms of both rare and common gene variants and environmental determinants of plasticity in the genotype-phenotype relationship with the ultimate goal of furthering our ability to identify, diagnose, risk stratify, and treat this group of disorders which cause heart failure and sudden death in the young.

  9. Genetics of inherited cardiomyopathy

    PubMed Central

    Jacoby, Daniel; McKenna, William J.

    2012-01-01

    During the past two decades, numerous disease-causing genes for different cardiomyopathies have been identified. These discoveries have led to better understanding of disease pathogenesis and initial steps in the application of mutation analysis in the evaluation of affected individuals and their family members. As knowledge of the genetic abnormalities, and insight into cellular and organ biology has grown, so has appreciation of the level of complexity of interaction between genotype and phenotype across disease states. What were initially thought to be one-to-one gene-disease correlates have turned out to display important relational plasticity dependent in large part on the genetic and environmental backgrounds into which the genes of interest express. The current state of knowledge with regard to genetics of cardiomyopathy represents a starting point to address the biology of disease, but is not yet developed sufficiently to supplant clinically based classification systems or, in most cases, to guide therapy to any significant extent. Future work will of necessity be directed towards elucidation of the biological mechanisms of both rare and common gene variants and environmental determinants of plasticity in the genotype–phenotype relationship with the ultimate goal of furthering our ability to identify, diagnose, risk stratify, and treat this group of disorders which cause heart failure and sudden death in the young. PMID:21810862

  10. Transgenerational inheritance of metabolic disease.

    PubMed

    Stegemann, Rachel; Buchner, David A

    2015-07-01

    Metabolic disease encompasses several disorders including obesity, type 2 diabetes, and dyslipidemia. Recently, the incidence of metabolic disease has drastically increased, driven primarily by a worldwide obesity epidemic. Transgenerational inheritance remains controversial, but has been proposed to contribute to human metabolic disease risk based on a growing number of proof-of-principle studies in model organisms ranging from Caenorhabditis elegans to Mus musculus to Sus scrofa. Collectively, these studies demonstrate that heritable risk is epigenetically transmitted from parent to offspring over multiple generations in the absence of a continued exposure to the triggering stimuli. A diverse assortment of initial triggers can induce transgenerational inheritance including high-fat or high-sugar diets, low-protein diets, various toxins, and ancestral genetic variants. Although the mechanistic basis underlying the transgenerational inheritance of disease risk remains largely unknown, putative molecules mediating transmission include small RNAs, histone modifications, and DNA methylation. Due to the considerable impact of metabolic disease on human health, it is critical to better understand the role of transgenerational inheritance of metabolic disease risk to open new avenues for therapeutic intervention and improve upon the current methods for clinical diagnoses and treatment.

  11. Transgenerational epigenetic inheritance in plants.

    PubMed

    Hauser, Marie-Theres; Aufsatz, Werner; Jonak, Claudia; Luschnig, Christian

    2011-08-01

    Interest in transgenerational epigenetic inheritance has intensified with the boosting of knowledge on epigenetic mechanisms regulating gene expression during development and in response to internal and external signals such as biotic and abiotic stresses. Starting with an historical background of scantily documented anecdotes and their consequences, we recapitulate the information gathered during the last 60 years on naturally occurring and induced epialleles and paramutations in plants. We present the major players of epigenetic regulation and their importance in controlling stress responses. The effect of diverse stressors on the epigenetic status and its transgenerational inheritance is summarized from a mechanistic viewpoint. The consequences of transgenerational epigenetic inheritance are presented, focusing on the knowledge about its stability, and in relation to genetically fixed mutations, recombination, and genomic rearrangement. We conclude with an outlook on the importance of transgenerational inheritance for adaptation to changing environments and for practical applications. This article is part of a Special Issue entitled "Epigenetic control of cellular and developmental processes in plants".

  12. Transgenerational Inheritance of Metabolic Disease

    PubMed Central

    Stegemann, Rachel; Buchner, David A.

    2015-01-01

    Metabolic disease encompasses several disorders including obesity, type 2 diabetes, and dyslipidemia. Recently, the incidence of metabolic disease has drastically increased, driven primarily by a worldwide obesity epidemic. Transgenerational inheritance remains controversial, but has been proposed to contribute to human metabolic disease risk based on a growing number of proof-of-principle studies in model organisms ranging from C. elegans to M. musculus to S. scrofa. Collectively, these studies demonstrate that heritable risk is epigenetically transmitted from parent to offspring over multiple generations in the absence of a continued exposure to the triggering stimuli. A diverse assortment of initial triggers can induce transgenerational inheritance including high-fat or high-sugar diets, low-protein diets, various toxins, and ancestral genetic variants. Although the mechanistic basis underlying the transgenerational inheritance of disease risk remains largely unknown, putative molecules mediating transmission include small RNAs, histone modifications, and DNA methylation. Due to the considerable impact of metabolic disease on human health, it is critical to better understand the role of transgenerational inheritance of metabolic disease risk to open new avenues for therapeutic intervention and improve upon the current methods for clinical diagnoses and treatment. PMID:25937492

  13. Transgenerational epigenetic inheritance in plants☆

    PubMed Central

    Hauser, Marie-Theres; Aufsatz, Werner; Jonak, Claudia; Luschnig, Christian

    2015-01-01

    Interest in transgenerational epigenetic inheritance has intensified with the boosting of knowledge on epigenetic mechanisms regulating gene expression during development and in response to internal and external signals such as biotic and abiotic stresses. Starting with an historical background of scantily documented anecdotes and their consequences, we recapitulate the information gathered during the last 60 years on naturally occurring and induced epialleles and paramutations in plants. We present the major players of epigenetic regulation and their importance in controlling stress responses. The effect of diverse stressors on the epigenetic status and its transgenerational inheritance is summarized from a mechanistic viewpoint. The consequences of transgenerational epigenetic inheritance are presented, focusing on the knowledge about its stability, and in relation to genetically fixed mutations, recombination, and genomic rearrangement. We conclude with an outlook on the importance of transgenerational inheritance for adaptation to changing environments and for practical applications. This article is part of a Special Issue entitled “Epigenetic control of cellular and developmental processes in plants”. PMID:21515434

  14. Inherited or acquired metabolic disorders.

    PubMed

    Eichler, Florian; Ratai, Eva; Carroll, Jason J; Masdeu, Joseph C

    2016-01-01

    This chapter starts with a description of imaging of inherited metabolic disorders, followed by a discussion on imaging of acquired toxic-metabolic disorders of the adult brain. Neuroimaging is crucial for the diagnosis and management of a number of inherited metabolic disorders. Among these, inherited white-matter disorders commonly affect both the nervous system and endocrine organs. Magnetic resonance imaging (MRI) has enabled new classifications of these disorders that have greatly enhanced both our diagnostic ability and our understanding of these complex disorders. Beyond the classic leukodystrophies, we are increasingly recognizing new hereditary leukoencephalopathies such as the hypomyelinating disorders. Conventional imaging can be unrevealing in some metabolic disorders, but proton magnetic resonance spectroscopy (MRS) may be able to directly visualize the metabolic abnormality in certain disorders. Hence, neuroimaging can enhance our understanding of pathogenesis, even in the absence of a pathologic specimen. This review aims to present pathognomonic brain MRI lesion patterns, the diagnostic capacity of proton MRS, and information from clinical and laboratory testing that can aid diagnosis. We demonstrate that applying an advanced neuroimaging approach enhances current diagnostics and management. Additional information on inherited and metabolic disorders of the brain can be found in Chapter 63 in the second volume of this series.

  15. Improved streamflow recession parameter estimation with attention to calculation of - dQ/dt

    NASA Astrophysics Data System (ADS)

    Roques, Clément; Rupp, David E.; Selker, John S.

    2017-10-01

    The rate of streamflow recession can be used to assess storage-outflow properties of source aquifers. A common method of analyzing streamflow recession is to plot the time rate of change in streamflow Q as a function of Q in a log-log space. Theory predicts, for diagnostic recession regimes, a power law relationship - dQ/dt = aQb, where recession coefficients a and b are functions of the hydraulic and geometric properties of the aquifer and of boundary and initial conditions. Observational error reduces the accuracy of estimates of a and b with errors in estimating the time derivative of the late-time recession (-dQ/dt) being particularly sensitive to observational error. Here we propose a method to improve estimation of a and b with particular focus on the estimation of -dQ/dt. Compared to previously published methods we find greater robustness in estimates of -dQ/dt and recession parameters and less sensitivity to the methodological parameters employed. Previous methods result in up to 50 to 100% error when estimating the recession parameter b, while the proposed methodology produces errors below 5% in the cases analyzed.

  16. Recessive hereditary deafness, assortative mating, and persistence of a sign language.

    PubMed

    Aoki, K; Feldman, M W

    1991-06-01

    We model the cultural transmission of sign language when there is one-locus genetic variation for deafness and hearing. Our premises are that the deaf are more motivated to learn sign language than the hearing, and that a vertically transmitted sign language, unlike recessive hereditary deafness, cannot "jump a generation." Conditions are obtained for persistence (i.e. protection from loss) of signers. These conditions are more easily satisfied the greater the fraction of the hearing who also learn sign language and as the frequency of the recessive gene for deafness increases. Persistence is also facilitated by assortative mating for deafness, but not by assortment for signing. With vertical transmission only, it is necessary that one signer parent be able to transmit sign language with greater than one-half the efficiency of two. Under the assumption that the hearing do not learn sign language, the following additional results are obtained. Persistence is more likely with dominant as opposed to recessive inheritance. When recessive hereditary and acquired deafness co-occur, increasing the frequency of the latter has opposite effects depending on the degree of assortment. Opportunities for the deaf to learn sign language outside the family seem not to affect the conditions for persistence.

  17. Confirmation of ADAMTSL4 mutations for autosomal recessive isolated bilateral ectopia lentis.

    PubMed

    Greene, V Bennouna; Stoetzel, C; Pelletier, V; Perdomo-Trujillo, Y; Liebermann, L; Marion, V; De Korvin, H; Boileau, C; Dufier, J L; Dollfus, H

    2010-03-01

    Ectopia lentis (EL) is a zonular disease where alteration of the zonular fibers leads progressively to lens dislocation. It is most often associated with systemic diseases such as Marfan syndrome, Weill-Marchesani syndrome or homocystinuria. Isolated non syndromic ectopia lentis (IEL) is reported in families with autosomal inheritance, with dominant forms being more common than recessive. LTBP2 truncating mutations have been described as a cause of autosomal recessive ectopia lentis as a primary or secondary feature in patients showing ocular (eg, glaucoma) or extraocular manifestations (eg, Marfanoid habitus). Recently, ADAMTSL4 has been shown to be responsible for isolated autosomal recessive ectopia lentis in an inbred family. Herein we show a consanguineous family that carries a novel homozygous splice mutation IVS4-1G>A/IVS4-1G>A in ADAMTSL4 responsible for isolated autosomal recessive EL, thus confirming the involvement of this gene in this condition and underlining the major role of ADAMTS proteases in zonular fibers homeostasis.

  18. A study of the inheritance of a bleeding disorder in Simmental cattle.

    PubMed Central

    Mapletoft, R J; Schmutz, S M; Searcy, G P

    2000-01-01

    A study was designed to determine the inheritance pattern of a blood platelet aggregation disorder in Simmental cattle utilizing embryo transfer technology. A Simmental donor cow that had previously produced a calf with the platelet aggregation disorder was superovulated and mated to a bull that had also produced affected offspring. Twenty-seven calves were produced from the 63 (42.9%) embryos transferred. This somewhat lower than expected pregnancy rate is suggestive of an increased rate of embryo loss. Twenty-three of 25 (92%) calves had normal platelet aggregation patterns and 2 failed to show any evidence of platelet aggregation. Data are suggestive that inheritance is not simple Mendelian recessive. A more likely scenario is that the defect is the result of the inheritance of at least 2 genes, which is also consistent with the sporadic incidence reported in the population at large. PMID:11062837

  19. Diagnosis and management of inherited cardiomyopathies.

    PubMed

    Millar, Lynne; Sharma, Sanjay

    2014-10-01

    Inherited heart conditions are the most common cause of sudden cardiac death in those under the age of 35 and the leading cause of non-traumatic death in young athletes. Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease affecting 1 in 500 of the population. Some patients may exhibit severe left ventricular hypertrophy, others may show nothing more than an abnormal ECG. Left ventricular hypertrophy most commonly manifests in the second decade of life. Sudden death is rare and usually affects patients in the first three decades whereas older patients present with heart failure, atrial fibrillation and stroke. Arrhythmogenic right ventricular cardiomyopathy is a rare, autosomal dominant heart muscle disorder which affects between 1 in 1,000 and 1 in 5,000 of the population. Dilated cardiomyopathy (DCM) is characterised by a dilated left ventricle with impaired function that cannot be explained by ischaemic heart disease, hypertension or valvular heart disease. At least 25% of cases of DCM are familial. DCM may be associated with multisystem conditions such as muscular dystrophy. Chemotherapy and certain other drugs, alcohol abuse and myocarditis may also lead to a dilated and poorly contracting left ventricle. In many cases the first manifestation of an inherited cardiomyopathy can be a sudden cardiac arrest. Other presentations include chest pain or breathlessness during exertion, palpitations and syncope. In many of the cardiomyopathies, the diagnosis can be made with a standard ECG and echocardiogram. However if the diagnosis is not certain or the cardiologist wishes to look at the heart structure in greater detail, a cardiac MRI may be performed.

  20. Highly effective SNP-based association mapping and management of recessive defects in livestock.

    PubMed

    Charlier, Carole; Coppieters, Wouter; Rollin, Frédéric; Desmecht, Daniel; Agerholm, Jorgen S; Cambisano, Nadine; Carta, Eloisa; Dardano, Sabrina; Dive, Marc; Fasquelle, Corinne; Frennet, Jean-Claude; Hanset, Roger; Hubin, Xavier; Jorgensen, Claus; Karim, Latifa; Kent, Matthew; Harvey, Kirsten; Pearce, Brian R; Simon, Patricia; Tama, Nico; Nie, Haisheng; Vandeputte, Sébastien; Lien, Sigbjorn; Longeri, Maria; Fredholm, Merete; Harvey, Robert J; Georges, Michel

    2008-04-01

    The widespread use of elite sires by means of artificial insemination in livestock breeding leads to the frequent emergence of recessive genetic defects, which cause significant economic and animal welfare concerns. Here we show that the availability of genome-wide, high-density SNP panels, combined with the typical structure of livestock populations, markedly accelerates the positional identification of genes and mutations that cause inherited defects. We report the fine-scale mapping of five recessive disorders in cattle and the molecular basis for three of these: congenital muscular dystony (CMD) types 1 and 2 in Belgian Blue cattle and ichthyosis fetalis in Italian Chianina cattle. Identification of these causative mutations has an immediate translation into breeding practice, allowing marker assisted selection against the defects through avoidance of at-risk matings.

  1. Recessive mutations in EPG5 cause Vici syndrome, a multisystem disorder with defective autophagy

    PubMed Central

    Cullup, Thomas; Kho, Ay L.; Dionisi-Vici, Carlo; Brandmeier, Birgit; Smith, Frances; Urry, Zoe; Simpson, Michael A.; Yau, Shu; Bertini, Enrico; McClelland, Verity; Al-Owain, Mohammed; Koelker, Stefan; Koerner, Christian; Hoffmann, Georg F.; Wijburg, Frits A.; Hoedt, Amber E. ten; Rogers, Curtis; Manchester, David; Miyata, Rie; Hayashi, Masaharu; Said, Elizabeth; Soler, Doriette; Kroisel, Peter M.; Windpassinger, Christian; Filloux, Francis M.; Al-Kaabi, Salwa; Hertecant, Jozef; Del Campo, Miguel; Buk, Stefan; Bodi, Istvan; Goebel, Hans-Hilmar; Sewry, Caroline A.; Abbs, Stephen; Mohammed, Shehla; Josifova, Dragana; Gautel, Mathias; Jungbluth, Heinz

    2012-01-01

    Vici syndrome is a recessively inherited multisystem disorder characterized by callosal agenesis, cataracts, cardiomyopathy, combined immunodeficiency and hypopigmentation. To investigate the molecular basis of Vici syndrome, we carried out exome and Sanger sequence analysis in a cohort of 18 patients. We identified recessive mutations in EPG5 (previously KIAA1632), indicating a causative role in Vici syndrome. EPG5 is the human homologue of the metazoan-specific autophagy gene epg-5, encoding a key autophagy regulator (ectopic P-granules autophagy protein 5) implicated in the formation of autolysosomes. Further studies demonstrated a severe block of autophagosomal clearance in muscle and fibroblasts from EPG5 mutant patients, resulting in autophagic cargo accumulation in autophagosomes. These findings indicate Vici syndrome as a paradigm of a human multisystem disorder associated with defective autophagy, and suggest a fundamental role of the autophagy pathway in the anatomical and functional formation of organs such as the brain, the heart and the immune system. PMID:23222957

  2. Using lod-score differences to determine mode of inheritance: A simple, robust method even in the presence of heterogeneity and reduced penetrance

    SciTech Connect

    Greenberg, D.A.; Berger, B.

    1994-10-01

    Determining the mode of inheritance is often difficult under the best of circumstances, but when segregation analysis is used, the problems of ambiguous ascertainment procedures, reduced penetrance, heterogeneity, and misdiagnosis make mode-of-inheritance determinations even more unreliable. The mode of inheritance can also be determined using a linkage-based method and association-based methods, which can overcome many of these problems. In this work, we determined how much information is necessary to reliably determine the mode of inheritance from linkage data when heterogeneity and reduced penetrance are present in the data set. We generated data sets under both dominant and recessive inheritance with reduced penetrance and with varying fractions of linked and unlinked families. We then analyzed those data sets, assuming reduced penetrance, both dominant and recessive inheritance, and no heterogeneity. We investigated the reliability of two methods for determining the mode of inheritance from the linkage data. The first method examined the difference ({Delta}) between the maximum lod scores calculated under the two mode-of-inheritance assumptions. We found that if {Delta} was >1.5, then the higher of the two maximum lod scores reflected the correct mode of inheritance with high reliability and that a {Delta} of 2.5 appeared to practically guarantee a correct mode-of-inheritance inference. Furthermore, this reliability appeared to be virtually independent of {alpha}, the fraction of linked families in the data set. The second method we tested was based on choosing the higher of the two maximum lod scores calculated under the different mode-of-inheritance assumptions. This method became unreliable as {alpha} decreased. These results suggest that the mode of inheritance can be inferred from linkage data with high reliability, even in the presence of heterogeneity and reduced penetrance. 12 refs., 3 figs., 2 tabs.

  3. Co-occurrence of non-mosaic trisomy 22 and inherited balanced t(4;6)(q33;q23.3) in a liveborn female: case report and review of the literature.

    PubMed

    Kehinde, Folasade I; Anderson, Carol E; McGowan, Jane E; Jethva, Reena N; Wahab, Mohammed A; Glick, Adina R; Sterner, Mark R; Pascasio, Judy M; Punnett, Hope H; Liu, Jinglan

    2014-12-01

    Trisomy 22 is the third most common autosomal trisomy occurring in about 0.4% of all clinically recognized pregnancies. Complete non-mosaic trisomy 22 is extremely rare in live births. Most affected children die before one year of age. To date, only 29 liveborn cases have been reported and none has carried an additional genetic lesion. In this report, we describe the clinical presentation, cytogenetic, and cytogenomic findings in a liveborn female with complete non-mosaic trisomy 22 as well as a paternally inherited, balanced reciprocal chromosomal rearrangement t(4;6)(q33;q23.3). The proband manifested features commonly seen in individuals with non-mosaic trisomy 22 such as intrauterine growth retardation (IUGR), single umbilical artery, cranial abnormalities, short neck, cleft lip and palate, dysmorphic ears, hypoplastic nipples, digital malformation, congenital heart defects, dysplastic kidneys, and genital anomalies. In addition, she had lobar holoprosencephaly, aqueductal stenosis, and limb and eye problems that have not been associated with complete trisomy 22 in previous reports. She died at 35 days of age of complex heart disease and renal failure. We are hereby expanding the cytogenetic and clinical spectrum of this rare chromosome disorder. Clinical features of liveborn children with non-mosaic trisomy 22 are reviewed and compared to those in our proband. The impact of genomic content in relation to the survival of trisomies in humans is also discussed.

  4. 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.

  5. 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

  6. Nonsense mutation in TMEM126A causing autosomal recessive optic atrophy and auditory neuropathy

    PubMed Central

    Meyer, Esther; Michaelides, Michel; Tee, Louise J.; Robson, Anthony G.; Rahman, Fatimah; Pasha, Shanaz; Luxon, Linda M.; Moore, Anthony T.

    2010-01-01

    Purpose To define the phenotype and elucidate the molecular basis for an autosomal recessively inherited optic atrophy and auditory neuropathy in a consanguineous family with two affected children. Methods Family members underwent detailed ophthalmologic, electrophysiological, and audiological assessments. An autozygosity mapping strategy using high-density single nucleotide polymorphism microarrays and microsatellite markers was used to detect regions of genome homozygosity that might contain the disease gene. Candidate genes were then screened for mutations by direct sequencing. Results Both affected subjects had poor vision from birth and complained of progressive visual loss over time. Current visual acuity ranged from 6/60 to 6/120. Fundus examination revealed bilateral temporal optic nerve pallor in both patients with otherwise normal retinal findings. International-standard full-field electroretinograms were normal in both individuals, with no evidence of generalized retinal dysfunction. Pattern cortical visual evoked potentials were grossly abnormal bilaterally in both cases. The pattern electroretinogram N95:P50 ratio was subnormal, and the P50 was of shortened peak time bilaterally in both patients. The electrophysiological findings were consistent with bilateral retinal ganglion cell/optic nerve dysfunction. Audiological investigation in both siblings revealed abnormalities falling within the auditory neuropathy/dysynchrony spectrum. There were no auditory symptoms and good outer hair cell function (as demonstrated by transient evoked otoacoustic emissions) but impaired inner hair cell/neural function with abnormal stapedial reflex thresholds and abnormal or absent auditory brainstem-evoked responses. The single nucleotide polymorphism microarray data demonstrated a 24.17 Mb region of homozygosity at 11q14.1–11q22.3, which was confirmed by microsatellite marker analysis. The candidate target region contained the transmembrane protein 126A (TMEM126A

  7. [Progresses in inheritance of genes for avian eggshell color].

    PubMed

    Yuan, Qing-Yan; Lu, Li-Zhi

    2007-03-01

    Eggshell has three colors: white, blue and brown. Chicken and duck eggs with blue eggshell have superior market for its better appearance, delicious taste, abundant nutrition and higher eggshell thickness and strength compared to those with white eggshell. However, error was often made when breeding blue-eggshell chicken or duck lines based on phenotypes. Studies on the forming and controlling mechanism of eggshell color had important theoretic and practical value. This review mainly discussed the types of eggshell color, its pigment composition and synthesis. Inheritance and heritability, genetic model, the number of genes, and the dominant-recessive relationship between genes for eggshell color were also reviewed. Information described in this review is useful for understanding the forming mechanism of eggshell color.

  8. GDAP1 mutations differ in their effects on mitochondrial dynamics and apoptosis depending on the mode of inheritance.

    PubMed

    Niemann, Axel; Wagner, Konstanze Marion; Ruegg, Marcel; Suter, Ueli

    2009-12-01

    Mutations in the GDAP1 gene lead to recessively or dominantly inherited peripheral neuropathies (Charcot-Marie-Tooth disease; CMT). Here, we demonstrate that GDAP1 is a mitochondrial fission factor whose activity is dependent on the fission factors Drp1 and Fis1. Unlike other mitochondrial fission factors, GDAP1 overexpression or knockdown does not influence the susceptibility of cells to apoptotic stimuli. Recessively inherited CMT-associated forms of GDAP1 (rmGDAP1s) have reduced fission activity, whereas dominantly inherited forms (dmGDAP1s) interfere with mitochondrial fusion. Only the expression of dmGDAP1s increases the production of ROS, leads to uneven mitochondrial transmembrane potentials, and enhances the susceptibility to apoptotic stimuli. Taken together, our results indicate that wild-type GDAP1 promotes fission without increasing the risk of apoptosis. In CMT, recessive GDAP1 mutations are associated with reduced fission activity, while dominant mutations impair mitochondrial fusion and cause mitochondrial damage. Thus, different cellular mechanisms that disturb mitochondrial dynamics underlie the similar clinical manifestations caused by GDAP1 mutations, depending on the mode of inheritance.

  9. Autosomal recessive micrencephaly with simplified gyral pattern, abnormal myelination and arthrogryposis.

    PubMed

    Sztriha, L; Al-Gazali, L I; Várady, E; Goebel, H H; Nork, M

    1999-06-01

    The clinical courses, neuroimaging and muscle biopsy findings of two infants born to an inbred Arab family are described. They had a syndrome of micrencephaly with simplified gyral pattern, abnormal myelin formation and arthrogryposis. Increased variation of fiber size was seen in the muscle biopsy, creatine kinase, however was normal. Large areas of muscle were replaced by adipofibrous tissue. The infants had dysmorphic features consistent with the fetal akinesia/hypokinesia sequence. The abnormalities were suggestive of microlissencephaly probably associated with a dysgenetic process in the muscles. The syndrome showed an autosomal recessive inheritance.

  10. Arthrogryposis, perthes disease, and upward gaze palsy: a novel autosomal recessive syndromic form of arthrogryposis.

    PubMed

    Alkuraya, Fowzan S

    2011-02-01

    In this article, the unusual combination of arthrogryposis, upward gaze palsy, and Perthes disease in two sisters and their cousin who are all part of an extended consanguineous Saudi family is reported. All patients had difficult to control bronchial asthma and subtle facial dysmorphism. Two of the three had pyloric stenosis, two were intellectually normal, and one had academic problems but had a history of birth hypoxia. Pedigree is consistent with an autosomal recessive mode of inheritance. Lack of previous reports suggests this represents a novel syndromic form of arthrogryposis. Copyright © 2010 Wiley-Liss, Inc.

  11. Epigenetic inheritance in rice plants.

    PubMed

    Akimoto, Keiko; Katakami, Hatsue; Kim, Hyun-Jung; Ogawa, Emiko; Sano, Cecile M; Wada, Yuko; Sano, Hiroshi

    2007-08-01

    Epigenetics is defined as mechanisms that regulate gene expression without base sequence alteration. One molecular basis is considered to be DNA cytosine methylation, which reversibly modifies DNA or chromatin structures. Although its correlation with epigenetic inheritance over generations has been circumstantially shown, evidence at the gene level has been limited. The present study aims to find genes whose methylation status directly correlates with inheritance of phenotypic changes. DNA methylation in vivo was artificially reduced by treating rice (Oryza sativa ssp. japonica) seeds with 5-azadeoxycytidine, and the progeny were cultivated in the field for > 10 years. Genomic regions with changed methylation status were screened by the methylation-sensitive amplified polymorphysm (MSAP) method, and cytosine methylation was directly scanned by the bisulfite mapping method. Pathogen infection with Xanthomonas oryzae pv. oryzae, race PR2 was performed by the scissors-dip method on mature leaf blades. The majority of seedlings were lethal, but some survived to maturity. One line designated as Line-2 showed a clear marker phenotype of dwarfism, which was stably inherited by the progeny over nine generations. MSAP screening identified six fragments, among which two were further characterized by DNA blot hybridization and direct methylation mapping. One clone encoding a retrotransposon gag-pol polyprotein showed a complete erasure of 5-methylcytosines in Line-2, but neither translocation nor expression of this region was detectable. The other clone encoded an Xa21-like protein, Xa21G. In wild-type plants, all cytosines were methylated within the promoter region, whereas in Line-2, corresponding methylation was completely erased throughout generations. Expression of Xa21G was not detectable in wild type but was constitutive in Line-2. When infected with X. oryzae pv. oryzae, against which Xa21 confers resistance in a gene-for-gene manner, the progeny of Line-2 were

  12. Coexistence of preeclampsia and inherited thrombophilia in Turkish pregnant women.

    PubMed

    Polat, Mehtap; Biberoğlu, Ebru Hacer; Güler, İsmail; Biberoğlu, Ömer Kutay

    2016-06-23

    To examine the relationship of inherited thrombophilia and other thrombotic risk factors with preeclampsia (PE) in a population of pregnant Turkish women. This was a case cross-sectional study in which 70 women with PE and 60 normal pregnant women were studied to find out the frequency of women with risk factors including inherited thrombophilia among preeclamptic cases. Hemoglobin, platelet count, uric acid, vitamin B12, folic acid, copper, homocysteine, plasminogen activator inhibitor-1, fibrinogen, protein S, protein C, activated protein C resistance values show significant differences in women with PE in comparison to women with normal pregnancy. There may be a link between inherited thrombophilia and PE, at least in a sample of Turkish pregnant women. We also propose that the association between thrombophilia and PE is stronger than suggested previously. Furthermore, copper is selectively elevated in women with PE as an independent marker.

  13. [How to understand the excessive lateral rectus muscle recession].

    PubMed

    Kang, Xiaoli; Wei, Yan

    2014-07-01

    Surgical treatments of intermittent exotropia include symmetric bilateral lateral rectus recession, symmetric bilateral medial rectus resection, asymmetric monocular lateral rectus recession and/or medial rectus resection, in which lateral rectus recession is the most common method. The maximum amount of lateral rectus recession, however, is still controversial. Bilateral lateral rectus recession 7-8 mm for 35(Δ)-40(Δ) exotropia and unilateral lateral rectus recession and medial rectus resection for exotropia larger than 40(Δ) are suggested by most doctor usually. But some other doctors advocated augmented bilateral lateral rectus recession (9-14 mm ) for exotropia larger than 50(Δ) or augmented unilateral lateral rectus recession for moderate angle exotropia (30(Δ)-35(Δ)), which brought confusion in practical clinical work. In this paper, we'll focus on the amount of lateral rectus recession, and discuss several common issues related to augmented lateral rectus recession, in order to provide references for the majority of clinicians.

  14. Inheritance of acquired traits in plants

    PubMed Central

    2010-01-01

    Since Lamarck proposed the idea of inheritance of acquired traits 200 years ago, much has been said for and against it, but the theory was finally declined after the 1930s. Despite of the negative opinions of the majority of geneticists, botanists and plant breeders have long recognized that altered properties during the growth were occasionally transmitted to the offspring. This was also the case with artificially altered properties such as dwarfism, flowering timing and plant stature, which were induced by a non-mutagenic chemical, 5-azacytidine and its derivatives. As these drugs are powerful inhibitors of DNA methylation in vivo, a close correlation between methylation and phenotypic expression was suggested. Subsequent studies showed that rice plants acquired disease resistance upon demethylation of the corresponding resistant gene, and that both resistant trait and hypomethylated status were inherited by the progeny up to nine generations. Whether or not the methylation pattern changes under natural condition was then questioned, and recent studies have indicated that it indeed naturally changes in response to environmental stresses. Whether or not the altered methylation pattern during the vegetative growth is heritable was also questioned, and studies on toadflax and rice affirmed the question, showing stable maintenance of hypermethylation in the former and hypomethylation in the latter for 250 and 10 years, respectively. The observation strongly suggested that acquired traits can be heritable as far as the acquired methylation pattern is stably transmitted. This concept is consistent with the Lamarck's theory of the inheritance of acquired traits, which therefore should be carefully reevaluated to reestablish his impaired reputation. PMID:20118668

  15. Automating Recession Curve Displacement Recharge Estimation.

    PubMed

    Smith, Brennan; Schwartz, Stuart

    2017-01-01

    Recharge estimation is an important and challenging element of groundwater management and resource sustainability. Many recharge estimation methods have been developed with varying data requirements, applicable to different spatial and temporal scales. The variability and inherent uncertainty in recharge estimation motivates the recommended use of multiple methods to estimate and bound regional recharge estimates. Despite the inherent limitations of using daily gauged streamflow, recession curve displacement methods provide a convenient first-order estimate as part of a multimethod hierarchical approach to estimate watershed-scale annual recharge. The implementation of recession curve displacement recharge estimation in the United States Geologic Survey (USGS) RORA program relies on the subjective, operator-specific selection of baseflow recession events to estimate a gauge-specific recession index. This paper presents a parametric algorithm that objectively automates this tedious, subjective process, parameterizing and automating the implementation of recession curve displacement. Results using the algorithm reproduce regional estimates of groundwater recharge from the USGS Appalachian Valley and Piedmont Regional Aquifer-System Analysis, with an average absolute error of less than 2%. The algorithm facilitates consistent, completely automated estimation of annual recharge that complements more rigorous data-intensive techniques for recharge estimation. © 2016, National Ground Water Association.

  16. Epigenetic Inheritance across the Landscape

    PubMed Central

    Whipple, Amy V.; Holeski, Liza M.

    2016-01-01

    The study of epigenomic variation at the landscape-level in plants may add important insight to studies of adaptive variation. A major goal of landscape genomic studies is to identify genomic regions contributing to adaptive variation across the landscape. Heritable variation in epigenetic marks, resulting in transgenerational plasticity, can influence fitness-related traits. Epigenetic marks are influenced by the genome, the environment, and their interaction, and can be inherited independently of the genome. Thus, epigenomic variation likely influences the heritability of many adaptive traits, but the extent of this influence remains largely unknown. Here, we summarize the relevance of epigenetic inheritance to ecological and evolutionary processes, and review the literature on landscape-level patterns of epigenetic variation. Landscape-level patterns of epigenomic variation in plants generally show greater levels of isolation by distance and isolation by environment then is found for the genome, but the causes of these patterns are not yet clear. Linkage between the environment and epigenomic variation has been clearly shown within a single generation, but demonstrating transgenerational inheritance requires more complex breeding and/or experimental designs. Transgenerational epigenetic variation may alter the interpretation of landscape genomic studies that rely upon phenotypic analyses, but should have less influence on landscape genomic approaches that rely upon outlier analyses or genome–environment associations. We suggest that multi-generation common garden experiments conducted across multiple environments will allow researchers to understand which parts of the epigenome are inherited, as well as to parse out the relative contribution of heritable epigenetic variation to the phenotype. PMID:27826318

  17. Utilizing inheritance in requirements engineering

    NASA Technical Reports Server (NTRS)

    Kaindl, Hermann

    1994-01-01

    The scope of this paper is the utilization of inheritance for requirements specification, i.e., the tasks of analyzing and modeling the domain, as well as forming and defining requirements. Our approach and the tool supporting it are named RETH (Requirements Engineering Through Hypertext). Actually, RETH uses a combination of various technologies, including object-oriented approaches and artificial intelligence (in particular frames). We do not attempt to exclude or replace formal representations, but try to complement and provide means for gradually developing them. Among others, RETH has been applied in the CERN (Conseil Europeen pour la Rechereche Nucleaire) Cortex project. While it would be impossible to explain this project in detail here, it should be sufficient to know that it deals with a generic distributed control system. Since this project is not finished yet, it is difficult to state its size precisely. In order to give an idea, its final goal is to substitute the many existing similar control systems at CERN by this generic approach. Currently, RETH is also tested using real-world requirements for the Pastel Mission Planning System at ESOC in Darmstadt. First, we outline how hypertext is integrated into a frame system in our approach. Moreover, the usefulness of inheritance is demonstrated as performed by the tool RETH. We then summarize our experiences of utilizing inheritance in the Cortex project. Lastly, RETH will be related to existing work.

  18. Inherited Retinal Degenerative Clinical Trial Network

    DTIC Science & Technology

    2009-10-01

    ending in blindness. In the United States, the total number of individuals affected by retinitis pigmentosa (RP) and other forms of rare inherited...AD_________________ AWARD NUMBER: W81XWH-07-1-0720 TITLE: Inherited Retinal Degenerative...Final 3. DATES COVERED 27 Sep 2007 – 29 Sep 2009 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Inherited Retinal Degenerative Clinical Trial Network

  19. Genetics of inherited primary arrhythmia disorders

    PubMed Central

    Spears, Danna A; Gollob, Michael H

    2015-01-01

    A sudden unexplained death is felt to be due to a primary arrhythmic disorder when no structural heart disease is found on autopsy, and there is no preceding documentation of heart disease. In these cases, death is presumed to be secondary to a lethal and potentially heritable abnormality of cardiac ion channel function. These channelopathies include congenital long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, Brugada syndrome, and short QT syndrome. In certain cases, genetic testing may have an important role in supporting a diagnosis of a primary arrhythmia disorder, and can also provide prognostic information, but by far the greatest strength of genetic testing lies in the screening of family members, who may be at risk. The purpose of this review is to describe the basic genetic and molecular pathophysiology of the primary inherited arrhythmia disorders, and to outline a rational approach to genetic testing, management, and family screening. PMID:26425105

  20. Inherited renal tubular defects with hypokalemia.

    PubMed

    Muthukrishnan, J; Modi, K D; Kumar, P Jagdish; Jha, Ratan

    2009-03-01

    Bartter's and Gitelman's syndrome are two ends of a spectrum of inherited renal tubular disorders that present with hypokalemic metabolic alkalosis of varying severity. Clinical features and associated calcium and magnesium ion abnormalities are used to diagnose these cases after excluding other commoner causes. We report on two cases, the first being a young boy, born of pregnancy complicated by polyhydramnios, who had classical dysmorphic features, polyuria, hypokalemia and hypercalciuria and was diagnosed as having Bartter's syndrome. The second patient is a lady who had recurrent tetany as the only manifestation of Gitelman's syndrome, which is an unusual presentation. Potassium replacement with supplementation of other deficient ions led to satisfactory clinical and biochemical response.

  1. Assessment of the genetic causes of recessive childhood non-syndromic deafness in the UK - implications for genetic testing.

    PubMed

    Hutchin, T; Coy, N N; Conlon, H; Telford, E; Bromelow, K; Blaydon, D; Taylor, G; Coghill, E; Brown, S; Trembath, R; Liu, X Z; Bitner-Glindzicz, M; Mueller, R

    2005-12-01

    Approximately one in 2000 children is born with a genetic hearing impairment, mostly inherited as a non-syndromic, autosomal recessive trait, for which more than 30 different genes have been identified. Previous studies have shown that one of these genes, connexin 26 (GJB2), accounts for 30-60% of such deafness, but the relative contribution of the many other genes is not known, especially in the outbred UK population. This lack of knowledge hampers the development of diagnostic genetic services for deafness. In an effort to determine the molecular aetiology of deafness in the population, 142 sib pairs with early-onset, non-syndromic hearing impairment were recruited. Those in whom deafness could not be attributed to GJB2 mutations were investigated further for other mapped genes. The genetic basis of 55 cases (38.7%) was established, 33.1% being due to mutations in the GJB2 gene and 3.5% due to mutations in SLC26A4. None of the remaining 26 loci investigated made a significant contribution to deafness in a Caucasian population. We suggest that screening the GJB2 and SLC26A4 genes should form the basis of any genetic testing programme for childhood deafness and highlight a number of important issues for consideration and future work.

  2. Cerebro-retinal microangiopathy with calcifications and cysts due to recessive mutations in the CTC1 gene.

    PubMed

    Bisserbe, A; Tertian, G; Buffet, C; Turhan, A; Lambotte, O; Nasser, G; Alvin, P; Tardieu, M; Riant, F; Bergametti, F; Tournier-Lasserve, E; Denier, C

    2015-05-01

    Cerebro-retinal microangiopathy with calcifications and cysts (CRMCC) or Coats plus syndrome is a pleiotropic disorder affecting the eyes, brain, bone and gastrointestinal tract. Its primary pathogenesis involves small vessel obliterative microangiopathy. Recently, autosomal recessively inherited mutations in CTC1 have been reported in CRMCC patients. We herein report an adolescent referred to our hospital following new seizures in a context of an undefined multisystem disorder. Cerebral imaging disclosed asymmetrical leukopathy, intracranial calcifications and cysts. In addition, he presented other typical CRMCC features i.e. a history of intrauterine growth retardation, skeletal demineralization and osteopenia, bilateral exudative vitreo-retinopathy reminiscent of Coats disease, recurrent gastrointestinal hemorrhages secondary to watermelon stomach and variceal bleeding of the esophagus due to idiopathic portal hypertension and telangiectatic and angiodysplasic changes in the small intestine and colon, and anemia due to recurrent bleeding and bone marrow abnormalities. The patient was diagnosed with Coats plus syndrome. CTC1 gene screening confirmed the diagnosis with the identification of heterozygous deleterious mutations. CRMCC due to CTC1 mutations has a broad clinical expressivity. Our case report illustrates the main possible associated phenotypes and their complications, demonstrating the need for a careful etiological search in order to initiate appropriate therapeutic and preventive measures. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  3. Cytoplasmic inheritance in Saccharomyces cerevisiae: comparison of zygotic mitochondrial inheritance patterns.

    PubMed

    Aufderheide, K J; Johnson, R G

    1976-03-30

    Mitochondrial movements in Saccharomyces cerevisiae (Sc) zygotes were monitored with phase-contrast microscopy and compared to known mitochondrial inheritance systems. The mitochondria of Sc were convincingly identified by integrated use of phase-contrast, cytochemical and electron microscopic observations. Mitochondria in Sc appear to move by saltatory jumps, which appear to be oriented towards movement of mitochondria into developing buds. Tracking of mitochondria of different genotypes was made possible by positive identification of each mitochondrial population before zygosis, and by the low degree of mixing (less than 10%) of mitochondrial populations before first bud septation. A grande by grande cross demonstrated equal numbers of mitochondria from each haploid moving into the first zygotic bud. A grande by neutral petite cross gave a 2:1 ratio of grande to petite mitochondria. However, a grande by suppressive petite cross gave equal numbers of grande and petite mitochondria. Using drug resistance systems, a comparison was made of highly biased (97%) and moderately biased (71%) chloramphenicol resistant inheritance patterns. In both cases, the ratios of drug resistant to sensitive mitochondria were 1:1. When numbers of mitochondria moving into an individual bud were compared to the phenotypic content of the clone of that bud, no model could be constructed which could predict the latter from the former. The data indicate (with the exception of the neutral petite by grande cross) that the numbers of each mitochondrial type "inserted" into the first zygotic bud are equal, regardless of the degree of asymmetry of inheritance of mitochondrial markers.

  4. A systematic review on the frequency of advanced recession following single immediate implant treatment.

    PubMed

    Cosyn, Jan; Hooghe, Nele; De Bruyn, Hugo

    2012-06-01

    It has been stated that midfacial recession is common following immediate implant treatment (IIT). The objective of this systematic review was to assess the frequency of advanced recession (>1 mm) following single IIT. An electronic search in Pubmed, Web of Science and the Cochrane Oral Health Group Specialized Trials Register database was performed using a search algorithm. Reference lists of relevant articles were also scrutinized to identify prospective studies on ≥10 implants installed in patients with an intact buccal bone wall and followed for ≥12 months. Study eligibility and quality were independently assessed by two investigators. Primary outcome variables were advanced inter-proximal and midfacial recession defined as soft tissue loss surpassing 1 mm between the pre- or postoperative status and the final re-assessment. Thirteen of 171 papers were selected. Inter-examiner agreement on eligibility (κ = 0.879; p < 0.001) and quality (κ = 0.788; p < 0.001) was high. Advanced inter-proximal recession was described in 0-27% of the cases. However, these data were only based on two studies. Mean inter-proximal recession was frequently reported (11/13) and was <1 mm in all studies suggesting limited risk for advanced inter-proximal recession. Advanced midfacial recession was described in 0-64% of the cases. Again, few papers provided such information (4/13). Only one of these studies demonstrated high risk for advanced midfacial recession (>10%). This could be attributed to the fact that implants had not been restored with an immediate implant crown, which seems of pivotal importance given the results of a randomized controlled trial reporting on the preserving effect of immediate provisionalization on midfacial mucosa level. There is limited evidence to support an increased risk for midfacial recession following flap surgery and in patients with a thin-scalloped gingival biotype. The impact of implant-specific parameters on inter-proximal and midfacial soft

  5. Identification and management of inherited cancer susceptibility.

    PubMed Central

    Li, F P

    1995-01-01

    Identification of inherited cancer-predisposing genes offers opportunities for cancer prevention. Inherited susceptibility genes have been identified, primarily through studies of unusual cancer cases and families but also through general population studies. Examples include the RB1 gene for retinoblastoma; the WT1 gene for Wilms' tumor; germline p53 mutations in families with the Li-Fraumeni syndrome; the NF1 and NF2 genes for neuroblastomatosis, types 1 and 2; the VHL gene for renal cancer and other tumors associated with Von Hippel-Lindau disease; the APC gene for adenomatous polyposis coli; the BRCA1 gene for hereditary breast and ovarian cancer; and the mismatch repair genes for colon and other common cancers. For some cancers, identification of gene carriers might be beneficial for targeting screening and chemopreventive interventions. On the other hand, predisposition testing for cancer has the potential for harm from loss of insurability and employability, psychological distress, social stigmatization and other adverse effects. Research is needed to identify predisposition testing procedures that maximize benefits while minimizing harm to subjects. Chemoprevention trials in genetically susceptible populations offer the prospect of finding effective methods of reducing future cancer risk. PMID:8741802

  6. Inherited tertiary hypothyroidism in Sprague-Dawley rats.

    PubMed

    Stoica, George; Lungu, Gina; Xie, Xueyi; Abbott, Louise C; Stoica, Heidi M; Jaques, John T

    2007-05-07

    Thyroid hormones (THs) are important in the development and maturation of the central nervous system (CNS). The significant actions of THs during CNS development occur at the time when TH levels are lower than those in the mother and the hypothalamic-thyroid (HPT) axis is not fully functional. In the developing rat nervous system, primarily the cerebellum, the first three postnatal weeks represent a period of significant sensitivity to thyroid hormones. This study presents a spontaneous, inherited recessive hypothyroidism in Sprague-Dawley rats with devastating functional consequences to the development of the CNS. The clinical signs develop around 14 day's postnatal (dpn) and are characterized by ataxia, spasticity, weight loss and hypercholesterolemia. The afflicted rats died at 30 days due to severe neurological deficits. The deterioration affects the entire CNS and is characterized by progressive neuronal morphological and biochemical changes, demyelination and astrogliosis. The cerebellum, brain stem, neocortex, hippocampus and adrenal gland medulla appear to be most affected. Thyroid Stimulating Hormone (TSH), T3 and T4 levels were significantly lower in hypothyroid rats than control. Immunohistochemistry and RT-PCR demonstrated a reduction of Thyrotropin Releasing Hormone (TRH) in the hypothalamus of hypothyroid rats. The weight of both thyroid and pituitary glands were significantly less in hypothyroid rats than the corresponding normal littermate controls. Transmission electron microscopy demonstrates consistent postsynaptic dendritic, synaptic and spine alterative changes in the brain of hypothyroid rats. These data suggest that we discovered a tertiary form of inherited hypothyroidism involving the hypothalamus.

  7. Large bimedial rectus recessions in congenital esotropia.

    PubMed Central

    Szmyd, S. M.; Nelson, L. B.; Calhoun, J. H.; Spratt, C.

    1985-01-01

    The success rate of large (6 and 7 mm) bimedial rectus recessions in 45 congenital esotropes with deviations of 50 prism dioptres or greater was found to be 91%. Judgment of final alignment was made six weeks postoperatively, with an average follow-up of 13 months. Large bimedial rectus recessions are an effective surgical treatment for congenital esotropia. This procedure does not significantly alter adduction, and leaves other muscles available should further surgery be necessary. These findings show that initial surgery on three or more muscles is unnecessary in congenital esotropia. PMID:3994944

  8. A neonate with Coombs-negative hemolytic jaundice with spherocytes but normal erythrocyte indices: a rare case of autosomal-recessive hereditary spherocytosis due to alpha-spectrin deficiency.

    PubMed

    Yaish, H M; Christensen, R D; Agarwal, A

    2013-05-01

    The diagnosis of hereditary spherocytosis (HS) in a newborn infant is generally made on the basis of a positive family history, spherocytes on blood film and Coombs-negative hemolytic jaundice of variable severity with an elevated mean corpuscular hemoglobin concentration (MCHC) and a low mean corpuscular volume (MCV). In general, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) quantification of erythrocyte membrane proteins is not needed to make the clinical diagnosis of HS. However, we observed that a neonate with no family history of HS, but with abundant spherocytosis on repeated blood films, Coombs-negative hemolytic jaundice and normal MCHC and MCV measurements, where SDS-PAGE revealed alpha-spectrin deficiency, a rare autosomal-recessive variety of HS that generally has a severe clinical phenotype.

  9. Mutations in KDSR Cause Recessive Progressive Symmetric Erythrokeratoderma.

    PubMed

    Boyden, Lynn M; Vincent, Nicholas G; Zhou, Jing; Hu, Ronghua; Craiglow, Brittany G; Bayliss, Susan J; Rosman, Ilana S; Lucky, Anne W; Diaz, Luis A; Goldsmith, Lowell A; Paller, Amy S; Lifton, Richard P; Baserga, Susan J; Choate, Keith A

    2017-06-01

    The discovery of new genetic determinants of inherited skin disorders has been instrumental to the understanding of epidermal function, differentiation, and renewal. Here, we show that mutations in KDSR (3-ketodihydrosphingosine reductase), encoding an enzyme in the ceramide synthesis pathway, lead to a previously undescribed recessive Mendelian disorder in the progressive symmetric erythrokeratoderma spectrum. This disorder is characterized by severe lesions of thick scaly skin on the face and genitals and thickened, red, and scaly skin on the hands and feet. Although exome sequencing revealed several of the KDSR mutations, we employed genome sequencing to discover a pathogenic 346 kb inversion in multiple probands, and cDNA sequencing and a splicing assay established that two mutations, including a recurrent silent third base change, cause exon skipping. Immunohistochemistry and yeast complementation studies demonstrated that the mutations cause defects in KDSR function. Systemic isotretinoin therapy has achieved nearly complete resolution in the two probands in whom it has been applied, consistent with the effects of retinoic acid on alternative pathways for ceramide generation. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  10. Homozygous mutation in MERTK causes severe autosomal recessive retinitis pigmentosa.

    PubMed

    Ksantini, Mohamed; Lafont, Estèle; Bocquet, Béatrice; Meunier, Isabelle; Hamel, Christian P

    2012-01-01

    Gene identification in retinitis pigmentosa is a prerequisite to future therapies. Accordingly, autosomal recessive retinitis pigmentosa families were genotyped to search for causative mutations. Members of a consanguineous Moroccan family had standard ophthalmologic examination, optical coherence tomography-3 scan, autofluorescence testing, and electroretinogram. Their DNA was genotyped with the 250K SNP microchip (Affymetrix) and homozygosity mapping was done. MERTK exons were polymerase chain reaction amplified and sequenced. Two sisters and one brother out of 6 siblings had rod cone dystrophy type of retinitis pigmentosa. Salient features were night blindness starting in early infancy, dot-like whitish deposits in fovea and macula with corresponding autofluorescent dots in youngest patients, decreased visual acuity, and cone responses higher than rod responses at electroretinogram. The patients were homozygous in regions from chromosomes 2 and 8, but only that of chromosome 2 was inherited from a common ancestor. Sequencing of the MERTK gene belonging to the chromosome 2 region showed that the 3 affected patients carried a novel homozygous mutation in exon 17, c.2323C>T, leading to p.Arg775X, while their unaffected brothers and sister, parents, and paternal grandfather were heterozygous. MERTK mutations lead to severe retinitis pigmentosa with discrete dot-like autofluorescent deposits at early stages, which are a hallmark of this MERTK-specific dystrophy.

  11. Autosomal recessive multiple pterygium syndrome: a new variant?

    PubMed

    Aslan, Y; Erduran, E; Kutlu, N

    2000-07-31

    Multiple pterygium syndromes include at least 15 different entities characterized by multiple pterygia or webs of the skin and multiple congenital anomalies. We describe a female infant who presented with a distinct constellation of multiple anomalies consisting of pterygia of the inguinal, intercrural and popliteal areas, flexion contractures and arthrogryposis of some joints, craniofacial anomalies including ectropion, medial canthal web, blepharophimosis, hypoplasia of nose, oral and nasopharyngeal cavities, vocal cords and tongue, micrognathia, orolabial synechiae secondary to pterygia, low set ears, alopecia, sad and expressionless face, short neck, asymmetric nipples, anal stenosis, rectal polyp, hypoplastic labia majora, complete syndactyly of all fingers and toes, pes equinovarus, bandlike web between feet, and absence of the nails and phalangeal-palmar creases. Radiological examination showed synostosis, absence or hypoplasia of metacarpal, metatarsal and phalangeal bones on feet and hands, and hypoplasia of pelvic bones and scapulae. This pattern of anomalies does not fit entirely any of the known multiple pterygium syndromes. Autosomal recessive inheritance is most likely due to the presence of three similarly affected siblings and normal parents.

  12. Exclusion of the locus for autosomal recessive pseudohypoaldosteronism type 1 from the mineralocorticoid receptor gene region on human chromosome 4q by linkage analysis

    SciTech Connect

    Chung, E.; Hanukoglu, A.; Rees, M.; Thompson, R.; Gardiner, R.M.

    1995-10-01

    Pseudohypoaldosteronism type 1 (PHA1) is an uncommon inherited disorder characterized by salt-wasting in infancy arising from target organ unresponsiveness to mineralocorticoids. Clinical expression of the disease varies from severely affected infants who may die to apparently asymptomatic individuals. Inheritance is Mendelian and may be either autosomal dominant or autosomal recessive. A defect in the mineralocortiocoid receptor has been implicated as a likely cause of PHA1. The gene for human mineralocorticoid receptor (MLR) has been cloned and physically mapped to human chromosome 4q31.1-31.2. The etiological role of MLR in autosomal recessive PHA1 was investigated by performing linkage analysis between PHA1 and three simple sequence length polymorphisms (D4S192, D4S1548, and D4S413) on chromosome 4q in 10 consanguineous families. Linkage analysis was carried out assuming autosomal recessive inheritance with full penetrance and zero phenocopy rate using the MLINK program for two-point analysis and the HOMOZ program for multipoint analysis. Lod scores of less than -2 were obtained over the whole region from D4S192 to D4S413 encompassing MLR. This provides evidence against MLR as the site of mutations causing PHA1 in the majority of autosomal recessive families. 34 refs., 3 figs., 2 tabs.

  13. [Ataxia telangiectasia. Diagnosis and follow-up in 4 cases].

    PubMed

    Monterrubio Ledezma, César Eduardo; Corona Rivera, Alfredo; Corona Rivera, Jorge Román; Rodríguez Casillas, Lourdes Jocelyn; Hernández Rocha, Juan; Barros Nuñez, Patricio; Bobadilla Morales, Lucina

    2013-01-01

    Ataxia telangiectasia (AT) is a chromosomal instability syndrome with autosomal recessive inheritance, it is caused by more than 500 mutations of the ATM gene, which is involved in the cellular response to DNA damage. The diagnosis becomes difficult due to the evolution of the disease, their poor knowledge, and limited access to diagnostic tests. Chromosomal damage induced by ionizing radiation (IR) assay is still a sensitive method for early diagnosis, and it is essential for better management and genetic counseling. This paper shows diagnosis and follow-up in four cases with AT.

  14. Living after sudden death: A case report of Naxos disease

    PubMed Central

    Noain, Jose Alberto Garcia; Golet, Amparo Cantin; Calzada, Jorge Navarro; Mellado, Ascension Muñoz; Duarte, Julian Mozota

    2012-01-01

    Naxos disease is a recessive inherited condition with arrhythmogenic right ventricular dysplasia (ARVD) and a peculiar cutaneous phenotype (woolly hair and a palmoplantar keratoderma). Woolly hair appears from birth, palmoplantar keratoderma develops during childhood and cardiomyopathy is clinically manifested by adolescence. Patients present with syncope, sustained ventricular tachycardia or sudden death. We report a case of a 14 year old boy from Spain, who was admitted into our emergency room after being resuscitated from cardiac arrest, secondary to malignant ventricular tachycardia that developed while he was playing basketball. PMID:23559728

  15. Bartter's syndrome in pregnancy: a case report and review.

    PubMed

    Li, I C; To, W W

    2000-04-01

    Bartter's syndrome is a rare renal tubular disorder, involving juxtaglomerular cells hyperplasia, characterized by normotensive hyper-reninism and secondary hyperaldosteronism, marked renal loss of potassium and profound hypokalaemia. Both clinical and biochemical features are heterogeneous, ranging from the incidental finding in an asymptomatic patient to marked clinical features of hypokalaemia. Inheritance is likely to be an autosomal recessive. We present a case of Bartter's syndrome complicating pregnancy in a Chinese woman. We documented an increasing demand for potassium supplement during pregnancy which stabilized by mid-trimester. The absence of pregnancy complications such as polyhydramnios indicated that the fetus was unlikely to be affected by the condition.

  16. Seasonal recession of Mars' south polar cap in 1986

    NASA Technical Reports Server (NTRS)

    James, Philip B.; Martin, Leonard J.; Henson, Jean R.; Birch, Peter V.

    1990-01-01

    Photographs of Mars obtained during the 1986 opposition of the planet have been used to derive the regression curve for the south polar cap between Ls = 190 deg and Ls = 255 deg. The 1986 regression appears to have been unexceptional until after Ls = 230 deg, when it becomes retarded relative to the normal established by the 1971 and 1977 regressions. A study of the data as a function of the filter used suggests that circumpolar clouds were present in early spring, unlike the case in the 1977 recession.

  17. Back to Biology: New Insights on Inheritance in Myeloproliferative Disorders

    PubMed Central

    Braunstein, Evan M.

    2015-01-01

    The myeloproliferative disorders (MPDs) are a group of hematologic diseases with significant overlap in both clinical phenotype and genetic etiology. While most often caused by acquired somatic mutations in hematopoietic stem cells, the presence of familial clustering in MPD cases suggests that inheritance is an important factor in the etiology of this disease. Though far less common than sporadic disease, inherited MPDs can be clinically indistinguishable from sporadic disease. Recently, germline mutations in Janus kinase 2 (JAK2) and MPL, two genes frequently mutated in sporadic MPD, have been shown to cause inherited thrombocytosis. Study of the function of these mutant proteins has led to a new understanding of the biological mechanisms that produce myeloproliferative disease. In this review, we summarize the data regarding inherited mutations that cause or predispose to MPDs, with a focus on the biological effects of mutant proteins. We propose that defining inherited MPDs in this manner has the potential to simplify diagnosis in a group of disorders that can be difficult to differentiate clinically. PMID:25195195

  18. A suggested mode of inheritance for wool shedding in sheep.

    PubMed

    Pollott, G E

    2011-08-01

    The ability of a sheep to shed its own wool has an attraction in scenarios where the costs of harvesting wool outweigh its value. Certain breeds and composites have the ability to shed their wool in the spring, and these are investigated in this work in an attempt to outline the genetics of wool shedding. One flock from a breeding group in Southern England (UK) containing sheep with wool-shedding characteristics provided shedding scores (1 to 5 scale; no shedding to complete shedding) that were used in a range of genetic analyses. The particular nature of wool shedding suggested that there may be a major gene segregating in these populations that facilitates wool shedding. In addition, there was clearly variation among wool shedders in the speed and extent of shedding, so a polygenic trait was also investigated. The breeding group used a range of shedding breeds and composites in a regular program to introduce wool-shedding genes into their flocks. This allowed the testing of Mendelian ratios for shedders:nonshedders in both first-cross and first-backcross animals. Four modes of inheritance were tested: autosomal recessive, sex-linked recessive, autosomal dominant, and sex-linked dominant. The most likely mode of inheritance was autosomal dominant (P < 0.05), with a low level of incomplete penetrance. In first back-cross animals, this mode of inheritance was confirmed but with complete penetrance. Approximately 11% of shedders did not exhibit the trait as lambs. Mixed-model analyses of shedding scores allowed an investigation of factors that affected wool shedding and also the extent of any genetic and permanent animal variance. Shedding score was found to have a heritability of 0.54 ± 0.07 in lambs and 0.26 ± 0.06 in animals of all ages in one flock using Easycare, Wiltshire Horn, Katahdin, and Dorper shedding animals. Shedding score as a lamb had a genetic correlation of 0.94 ± 0.08 with shedding score as a 2 yr old, but at the phenotypic level this

  19. The Recesses of the Sellar Wall of the Sphenoid Sinus and Their Intracranial Relationships.

    PubMed

    Peris-Celda, Maria; Kucukyuruk, Baris; Monroy-Sosa, Alejandro; Funaki, Takeshi; Valentine, Rowan; Rhoton, Albert L

    2013-02-19

    BACKGROUND:: The sellar wall of the sphenoid sinus and its recesses have been previously studied, but their intracranial relationships to the diaphragma sellae, tuberculum, clinoid segment of the internal carotid artery, chiasmatic sulcus, and middle clinoid process need further definition. OBJECTIVE:: To describe these intra and extracranial relationships of the recesses in the anterior sellar wall. METHODS:: The middle clinoid was studied in 132 parasellar areas of dry skulls. Thirty-eight parasellar areas of formalin-fixed/silicone-colored specimens were dissected. After transsphenoidal endoscopic exposure, the optic, carotid, and sellar prominences; lateral opticocarotid and tuberculum recesses; and caroticosellar and medial opticocarotid points were identified. High-speed drills opened 1 mm perforations at these points to allow study of intracranial relationships. RESULTS:: Two recesses and two junction points can be recognized in the sphenoid sinus: lateral opticocarotid and tuberculum recesses and medial opticocarotid and caroticosellar points. The lateral opticocarotid recess corresponds to the optic strut base, and the clinoid segment of the internal carotid artery is located medially. The diaphragma sellae attachment is at the level of the tuberculum recess, which in 50% of cases corresponds to the tuberculum. A middle clinoid in base or height greater than 1.5 mm is present in 21.1% and a caroticoclinoid ring in 3%. The middle clinoid is 1 mm inferior and lateral to the caroticosellar point and 4.7 mm inferior to the medial opticocarotid point. CONCLUSION:: An understanding of the intra and extracranial relationships of the recesses of the sphenoid sinus will aid in accurately directing transsphenoidal approaches.

  20. Familial occurrence of Danish and Dutch cases of the bovine brachyspina syndrome

    PubMed Central

    Agerholm, Jørgen S; Peperkamp, Klaas

    2007-01-01

    Background The bovine brachyspina syndrome is a recently reported malformation in the Holstein breed. The aetiology of this syndrome is unknown, but its occurrence following breeding between genetically related and phenotypically normal cattle may indicate that it is an autosomal recessively inherited disorder. Three cases are reported and compared to the originally reported case. Case presentation Two Danish cases and a Dutch case are described. The calves were delivered following a slightly prolonged gestation period. Gross lesions consisted of growth retardation, significant shortening of the entire spine and long and slender limbs. Additionally, inferior brachygnatism and defects of several internal organs were recorded. The cases were diagnosed as having the brachyspina syndrome based on the presence of essential lesions. The parents of each case were genetically related and linked to the first reported case by a common ancestor. Conclusion The findings support the hypothesis that the brachyspina syndrome in Holstein cattle is inherited autosomal recessively and illustrate some of the assumed phenotypical variation of this syndrome. The brachyspina syndrome may be an emerging disease in the Holstein breed. PMID:17488494

  1. Mitochondrial inheritance in budding yeast.

    PubMed

    Boldogh, I R; Yang, H C; Pon, L A

    2001-06-01

    During the past decade significant advances were made toward understanding the mechanism of mitochondrial inheritance in the yeast Saccharomyces cerevisiae. A combination of genetics, cell-free assays and microscopy has led to the discovery of a great number of components. These fall into three major categories: cytoskeletal elements, mitochondrial membrane components and regulatory proteins. These proteins mediate activities, including movement of mitochondria from mother cells to buds, segregation of mitochondria and mitochondrial DNA, and equal distribution of the organelle between mother cells and buds during yeast cell division.

  2. Detection of new paternal dystrophin gene mutations in isolated cases of dystrophinopathy in females

    SciTech Connect

    Pegoraro, E.; Wessel, H.B.; Schwartz, L.; Hoffman, E.P. ); Schimke, R.N. ); Arahata, Kiichi; Hayashi, Yukiko ); Stern, H. ); Marks, H. ); Glasberg, M.R. )

    1994-06-01

    Duchenne muscular dystrophy is one of the most common lethal monogenic disorders and is caused by dystrophin deficiency. The disease is transmitted as an X-linked recessive trait; however, recent biochemical and clinical studies have shown that many girls and women with a primary myopathy have an underlying dystrophinopathy, despite a negative family history for Duchenne dystrophy. These isolated female dystrophinopathy patients carried ambiguous diagnoses with presumed autosomal recessive inheritance (limb-girdle muscular dystrophy) prior to biochemical detection of dystrophin abnormalities in their muscle biopsy. It has been assumed that these female dystrophinopathy patients are heterozygous carries who show preferential inactivation of the X chromosome harboring the normal dystrophin gene, although this has been shown for only a few X:autosome translocations and for two cases of discordant monozygotic twin female carriers. Here the authors study X-inactivation patterns of 13 female dystrophinopathy patients - 10 isolated cases and 3 cases with a positive family history for Duchenne dystrophy in males. They show that all cases have skewed X-inactivation patterns in peripheral blood DNA. Of the nine isolated cases informative in the assay, eight showed inheritance of the dystrophin gene mutation from the paternal germ line. Only a single case showed maternal inheritance. The 10-fold higher incidence of paternal transmission of dystrophin gene mutations in these cases is at 30-fold variance with Bayesian predictions and gene mutation rates. Thus, the results suggest some mechanistic interaction between new dystrophin gene mutations, paternal inheritance, and skewed X inactivation. The results provide both empirical risk data and a molecular diagnostic test method, which permit genetic counseling and prenatal diagnosis of this new category of patients. 58 refs., 7 figs., 2 tabs.

  3. [Periodontology and esthetics: the gingival recession].

    PubMed

    Corba, N H

    1991-06-01

    Gingival recessions are regarded by many people as an esthetical problem. Successively the etiology, the significance and the indications for therapy are discussed. Different kinds of therapy such as oral hygiene instruction, the free gingival graft and various pedicle grafts are explained. Finally it is advocated that surgical kinds of therapy have to be applied with reservedness.

  4. Weathering the recession in college health.

    PubMed

    Christmas, William A

    2010-01-01

    The current global recession has increased personal stress levels throughout our society. With dwindling resources, institutions of higher learning are especially prone to budgetary cutbacks during such periods. Based on 22 years of experience as a health service director, the author offers some personal insights in the hope that they will help colleagues cope with the current situation.

  5. Weathering the Recession in College Health

    ERIC Educational Resources Information Center

    Christmas, William A.

    2010-01-01

    The current global recession has increased personal stress levels throughout our society. With dwindling resources, institutions of higher learning are especially prone to budgetary cutbacks during such periods. Based on 22 years of experience as a health service director, the author offers some personal insights in the hope that they will help…

  6. Weathering the Recession in College Health

    ERIC Educational Resources Information Center

    Christmas, William A.

    2010-01-01

    The current global recession has increased personal stress levels throughout our society. With dwindling resources, institutions of higher learning are especially prone to budgetary cutbacks during such periods. Based on 22 years of experience as a health service director, the author offers some personal insights in the hope that they will help…

  7. Naval stores markets on hold during recession

    SciTech Connect

    Layman, P.

    1982-03-22

    A review of the current state of the market and level of inventory stocks of turpentine and tall oil and its derivatives. It is concluded that pricing is soft as major markets suffer through recession, but that recovery may be quick in some areas where inventory stocks are low.

  8. The Global Picture. Recession to Recovery

    ERIC Educational Resources Information Center

    Universities UK, 2010

    2010-01-01

    The objectives of this study were to: (1) document government and HE (higher education) sector responses to the recession within a select number of key countries which compete with the UK; and (2) compare these responses and analyse them by theme to draw out any common patterns. The focus of the work was to find, where possible, an evidence base…

  9. The Recession and Education: Seize New Opportunities!

    ERIC Educational Resources Information Center

    Haskvitz, Alan

    2011-01-01

    The teaching profession has long been thought of as recession proof. Indeed, that may have been one of the reasons why teachers took far lower starting salaries right out of college. Perhaps the greatest common feature of teachers, besides their desire to serve society in a humanitarian way, may be the lack of risk-taking the occupation previously…

  10. Recession curbs gas pipeline construction costs

    SciTech Connect

    Morgan, J.M.

    1983-01-24

    This paper shows how after 5 yrs. of inflation, gas pipeline construction costs have finally felt the effects of a severe building recession. First quarter (1982) construction activity, compressor equipment and drive units, and high-pressure gas-station piping are discussed. Graphs of OGJ-Morgan composite gas pipeline cost, and gas pipeline cost component indexes are presented.

  11. Gender Differences during Recess in Elementary Schools.

    ERIC Educational Resources Information Center

    Twarek, Linda S.; George, Halley S.

    A study examined the differences in what boys and girls choose, or are free to choose, to do on the playground during recess. Given the apparent problem that boys dominate the playground area, leaving girls on the perimeter, it was hypothesized that girls engage in passive, non-competitive, small group activities, whereas boys engage in…

  12. The Global Picture. Recession to Recovery

    ERIC Educational Resources Information Center

    Universities UK, 2010

    2010-01-01

    The objectives of this study were to: (1) document government and HE (higher education) sector responses to the recession within a select number of key countries which compete with the UK; and (2) compare these responses and analyse them by theme to draw out any common patterns. The focus of the work was to find, where possible, an evidence base…

  13. Recess for Students with Visual Impairments

    ERIC Educational Resources Information Center

    Lucas, Matthew D.

    2010-01-01

    During recess, the participation of a student with visual impairments in terms of movement can often be both challenging and rewarding for the student and general education teacher. This paper will address common characteristics of students with visual impairments and present basic solutions to improve the participation of these students in the…

  14. AAV-mediated gene therapy in mouse models of recessive retinal degeneration

    PubMed Central

    Pang, Ji-jing; Lei, Lei; Dai, Xufeng; Shi, Wei; Liu, Xuan; Dinculescu, Astra; McDowell, J. Hugh

    2013-01-01

    In recent years, more and more mutant genes that cause retinal diseases have been detected. At the same time, many naturally occurring mouse models of retinal degeneration have also been found, which show similar changes to human retinal diseases. These, together with improved viral vector quality allow more and more traditionally incurable inherited retinal disorders to become potential candidates for gene therapy. Currently, the most common vehicle to deliver the therapeutic gene into target retinal cells is the adeno-associated viral vector (AAV). Following delivery to the immuno-priviledged subretinal space, AAV-vectors can efficiently target both retinal pigment epithelium and photoreceptor cells, the origin of most retinal degenerations. This review focuses on the AAV-based gene therapy in mouse models of recessive retinal degenerations, especially those in which delivery of the correct copy of the wild-type gene has led to significant beneficial effects on visual function, as determined by morphological, biochemical, electroretinographic and behavioral analysis. The past studies in animal models and ongoing successful LCA2 clinical trials, predict a bright future for AAV gene replacement treatment for inherited recessive retinal diseases. PMID:22300136

  15. Exome sequencing and directed clinical phenotyping diagnose cholesterol ester storage disease presenting as autosomal recessive hypercholesterolemia

    PubMed Central

    Stitziel, Nathan O.; Fouchier, Sigrid W.; Sjouke, Barbara; Peloso, Gina M.; Moscoso, Alessa M.; Auer, Paul L.; Goel, Anuj; Gigante, Bruna; Barnes, Timothy A.; Melander, Olle; Orho-Melander, Marju; Duga, Stefano; Sivapalaratnam, Suthesh; Nikpay, Majid; Martinelli, Nicola; Girelli, Domenico; Jackson, Rebecca D.; Kooperberg, Charles; Lange, Leslie A.; Ardissino, Diego; McPherson, Ruth; Farrall, Martin; Watkins, Hugh; Reilly, Muredach P.; Rader, Daniel J.; de Faire, Ulf; Schunkert, Heribert; Erdmann, Jeanette; Samani, Nilesh J.; Charnas, Lawrence; Altshuler, David; Gabriel, Stacey; Kastelein, John J.P.; Defesche, Joep C.; Nederveen, Aart J.; Kathiresan, Sekar; Hovingh, G. Kees

    2014-01-01

    Objective Autosomal recessive hypercholesterolemia (ARH) is a rare inherited disorder characterized by extremely high total and low-density lipoprotein cholesterol levels that has been previously linked to mutations in LDLRAP1. We identified a family with ARH not explained by mutations in LDLRAP1 or other genes known to cause monogenic hypercholesterolemia. The aim of this study was to identify the molecular etiology of ARH in this family. Approach and Results We used exome sequencing to assess all protein coding regions of the genome in three family members and identified a homozygous exon 8 splice junction mutation (c.894G>A, also known as E8SJM) in LIPA that segregated with the diagnosis of hypercholesterolemia. Since homozygosity for mutations in LIPA is known to cause cholesterol ester storage disease (CESD), we performed directed follow-up phenotyping by non-invasively measuring hepatic cholesterol content. We observed abnormal hepatic accumulation of cholesterol in the homozygote individuals, supporting the diagnosis of CESD. Given previous suggestions of cardiovascular disease risk in heterozygous LIPA mutation carriers, we genotyped E8SJM in >27,000 individuals and found no association with plasma lipid levels or risk of myocardial infarction, confirming a true recessive mode of inheritance. Conclusions By integrating observations from Mendelian and population genetics along with directed clinical phenotyping, we diagnosed clinically unapparent CESD in the affected individuals from this kindred and addressed an outstanding question regarding risk of cardiovascular disease in LIPA E8SJM heterozygous carriers. PMID:24072694

  16. Assessment of Inheritance and Fitness Costs Associated with Field-Evolved Resistance to Cry3Bb1 Maize by Western Corn Rootworm.

    PubMed

    Paolino, Aubrey R; Gassmann, Aaron J

    2017-05-11

    The western corn rootworm, Diabrotica virgifera virgifera LeConte, is among the most serious insect pests of maize in North America. One strategy used to manage this pest is transgenic maize that produces one or more crystalline (Cry) toxins derived from the bacterium Bacillus thuringiensis (Bt). To delay Bt resistance by insect pests, refuges of non-Bt maize are grown in conjunction with Bt maize. Two factors influencing the success of the refuge strategy to delay resistance are the inheritance of resistance and fitness costs, with greater delays in resistance expected when inheritance of resistance is recessive and fitness costs are present. We measured inheritance and fitness costs of resistance for two strains of western corn rootworm with field-evolved resistance to Cry3Bb1 maize. Plant-based and diet-based bioassays revealed that the inheritance of resistance was non-recessive. In a greenhouse experiment, in which larvae were reared on whole maize plants in field soil, no fitness costs of resistance were detected. In a laboratory experiment, in which larvae experienced intraspecific and interspecific competition for food, a fitness cost of delayed larval development was identified, however, no other fitness costs were found. These findings of non-recessive inheritance of resistance and minimal fitness costs, highlight the potential for the rapid evolution of resistance to Cry3Bb1 maize by western corn rootworm, and may help to improve resistance management strategies for this pest.

  17. [Spontaneous rupture of common iliac artery: a case of Ehlers-Danlos syndrome and review of the literature].

    PubMed

    Bronzino, P; Abbo, L; Bagnasco, F; Barisone, P; Dezzani, C; Genovese, A M; Iannucci, P; Ippoliti, M; Sacchi, M; Aimo, I

    2006-01-01

    Authors report an uncommon case of spontaneous rupture of common iliac artery in a man 43 years old with Ehlers-Danlos syndrome. The clinical presentation was devious in the beginning and catastrophic after few hours with a haemo-peritoneum and haemorragic shock. The Ehlers-Danlos syndrome is a rare affection of the connective tissue with an incidence of 1/5000, representing one of the most common disorders of the connective tissue. This disease is characterized by the fragility of arteries, intestine and uterus. Its presentation is often catastrophic, with rupture of a big artery, rupture of uterus during pregnancy or bowel perforation. The mean age of death in subjects with Ehlers-Danlos syndrome is 45 years. This syndrome is inherited in most cases in an autosomal dominant manner; 50% of the cases are due to new mutations. A minority of cases, due to deficit of tenascina X, is inherited in an autosomal recessive manner.

  18. The Inherited Bone Marrow Failure Syndromes

    PubMed Central

    Chirnomas, S. Deborah; Kupfer, Gary M

    2013-01-01

    In spite of the rarity of inherited bone marrow failure syndromes (IBMFS), they represent diseases for which the molecular pathogenesis may be elucidated. Their study and presentation of the details of their molecular biology and biochemistry is warranted not only for appropriate diagnosis and management of afflicted patients but also because they lend clues to the normal physiology of the normal hematopoiesis and, in many cases, mechanisms of carcinogenesis. Several themes have emerged within each subsection of IBMFS, including the ribosomopathies that entail both ribosome assembly as well as ribosomal RNA processing. The Fanconi anemia (FA) pathway itself has become interdigitated with the familial breast cancer syndromes. The sections that follow present a more detailed analysis of the diseases that account for the majority of IBMFS diagnoses. PMID:24237972

  19. Paternal inheritance of mitochondria in Chlamydomonas.

    PubMed

    Nakamura, Soichi

    2010-03-01

    To analyze mitochondrial DNA (mtDNA)inheritance, differences in mtDNA between Chlamydomonas reinhardtii and Chlamydomonas smithii, respiration deficiency and antibiotic resistance were used to distinguish mtDNA origins. The analyses indicated paternal inheritance. However, these experiments raised questions regarding whether paternal inheritance occurred normally.Mitochondrial nucleoids were observed in living zygotes from mating until 3 days after mating and then until progeny formation. However, selective disappearance of nucleoids was not observed. Subsequently, experimental serial backcrosses between the two strains demonstrated strict paternal inheritance. The fate of mt+ and mt- mtDNA was followed using the differences in mtDNA between the two strains. The slow elimination of mt+ mtDNA through zygote maturation in darkness was observed, and later the disappearance of mt+ mtDNA was observed at the beginning of meiosis. To explain the different fates of mtDNA, methylation status was investigated; however, no methylation was detected. Variously constructed diploid cells showed biparental inheritance. Thus, when the mating process occurs normally, paternal inheritance occurs. Mutations disrupting mtDNA inheritance have not yet been isolated. Mutations that disrupt maternal inheritance of chloroplast DNA (cpDNA) do not disrupt inheritance of mtDNA. The genes responsible for mtDNA inheritance are different from those of chloroplasts.

  20. Atypical mitochondrial inheritance patterns in eukaryotes.

    PubMed

    Breton, Sophie; Stewart, Donald T

    2015-10-01

    Mitochondrial DNA (mtDNA) is predominantly maternally inherited in eukaryotes. Diverse molecular mechanisms underlying the phenomenon of strict maternal inheritance (SMI) of mtDNA have been described, but the evolutionary forces responsible for its predominance in eukaryotes remain to be elucidated. Exceptions to SMI have been reported in diverse eukaryotic taxa, leading to the prediction that several distinct molecular mechanisms controlling mtDNA transmission are present among the eukaryotes. We propose that these mechanisms will be better understood by studying the deviations from the predominating pattern of SMI. This minireview summarizes studies on eukaryote species with unusual or rare mitochondrial inheritance patterns, i.e., other than the predominant SMI pattern, such as maternal inheritance of stable heteroplasmy, paternal leakage of mtDNA, biparental and strictly paternal inheritance, and doubly uniparental inheritance of mtDNA. The potential genes and mechanisms involved in controlling mitochondrial inheritance in these organisms are discussed. The linkage between mitochondrial inheritance and sex determination is also discussed, given that the atypical systems of mtDNA inheritance examined in this minireview are frequently found in organisms with uncommon sexual systems such as gynodioecy, monoecy, or andromonoecy. The potential of deviations from SMI for facilitating a better understanding of a number of fundamental questions in biology, such as the evolution of mtDNA inheritance, the coevolution of nuclear and mitochondrial genomes, and, perhaps, the role of mitochondria in sex determination, is considerable.

  1. Digenic inheritance in medical genetics.

    PubMed

    Schäffer, Alejandro A

    2013-10-01

    Digenic inheritance (DI) is the simplest form of inheritance for genetically complex diseases. By contrast with the thousands of reports that mutations in single genes cause human diseases, there are only dozens of human disease phenotypes with evidence for DI in some pedigrees. The advent of high-throughput sequencing (HTS) has made it simpler to identify monogenic disease causes and could similarly simplify proving DI because one can simultaneously find mutations in two genes in the same sample. However, through 2012, I could find only one example of human DI in which HTS was used; in that example, HTS found only the second of the two genes. To explore the gap between expectation and reality, I tried to collect all examples of human DI with a narrow definition and characterise them according to the types of evidence collected, and whether there has been replication. Two strong trends are that knowledge of candidate genes and knowledge of protein-protein interactions (PPIs) have been helpful in most published examples of human DI. By contrast, the positional method of genetic linkage analysis, has been mostly unsuccessful in identifying genes underlying human DI. Based on the empirical data, I suggest that combining HTS with growing networks of established PPIs may expedite future discoveries of human DI and strengthen the evidence for them.

  2. Autosomal dominant inheritance of Brachmann-de Lange syndrome

    SciTech Connect

    Kozma, C.

    1996-12-30

    A mother with mild phenotype and her severely affected son, both with classic manifestations of Brachmann-de Lange syndrome (BDLS), are described. This documented mother-to-child transmission supports the hypothesis of autosomal dominant transmission with intrafamilial variability. Known cases of BDLS with autosomal dominant inheritance are reviewed. Although most cases of BDLS are sporadic, a careful evaluation of parents of affected children is important for appropriate genetic counseling. 15 refs., 3 figs., 1 tab.

  3. Bluff formation and long-term recession rates, southwestern Lake Michigan

    SciTech Connect

    Rovey, C.W. II )

    1992-01-01

    Where eroding cohesive sediments are present, Lake Michigan bluffs range up to 140 ft. in height and expose multiple stratigraphic units. According to the model presented here, bluffs form as a wave cut terrace erodes inland from a point near the original shoreline. The erosion plane is nearly horizontal, in contrast with the eastward dip of the glacial units inherited from underlying bedrock. Therefore, terraces eroding inland (west) produce progressively higher bluffs and expose successively older units at the toe and beneath the lake. This process repeated several times as lake levels sequentially dropped to their modern stage. The initial modern shoreline, and hence the width of the wave cut terrace, was determined from 4 offshore seismic profiles. It is picked as an inflection point in the slope of the lake bed, occurring offshore of dipping reflectors intersecting the lake bottom. The calculated average recession rate over the 2,500 year duration of the modern stage is 5 ft/yr in contrast to average rates of 2 ft/yr measured over the last century. Thus rates decrease through time as the terrace widens and wave energy is damped. By correlating bluff height to amount of recession of modern bluffs, a third rate of 12 ft/yr of the first 800 years of a recession is calculated for relict bluffs formed at the Nipissing II level. The 3 rates define a steeply decaying exponential curve in early stages of bluff retreat, flattening into a nearly linear function after 1,000 years.

  4. Genetic screening of Congenital Short Bowel Syndrome patients confirms CLMP as the major gene involved in the recessive form of this disorder.

    PubMed

    Alves, Maria M; Halim, Danny; Maroofian, Reza; de Graaf, Bianca M; Rooman, Raoul; van der Werf, Christine S; Van de Vijver, Els; Mehrjardi, Mohammad Yv; Aflatoonian, Majid; Chioza, Barry A; Baple, Emma L; Dehghani, Mohammadreza; Crosby, Andrew H; Hofstra, Robert Mw

    2016-11-01

    Congenital short bowel syndrome (CSBS) is an intestinal pediatric disorder, where patients are born with a dramatic shortened small intestine. Pathogenic variants in CLMP were recently identified to cause an autosomal recessive form of the disease. However, due to the rare nature of CSBS, only a small number of patients have been reported to date with variants in this gene. In this report, we describe novel inherited variants in CLMP in three CSBS patients derived from two unrelated families, confirming CLMP as the major gene involved in the development of the recessive form of CSBS.

  5. Congenital Cutis Laxa Type 2 Associated With Recurrent Aspiration Pneumonia and Growth Delay: Case Report.

    PubMed

    Rahmati, Mohammadbagher; Yazdanparast, Maryam; Jahanshahi, Keramatallah; Zakeri, Mohadese

    2015-10-01

    Cutis laxa is a connective tissue disorder caused by deficiency of fibro elastic plexus, which can involve multiple organs. It is inherited in autosomal dominant, autosomal recessive, and X-linked. Autosomal recessive cutis laxa type 2, which appears to compromise a spectrum of disorders, starts with severe wrinkly skin syndrome and leads to more severe diseases related to growth and developmental delays and skeletal anomalies. The clinical manifestations in some of cases of Cutis laxa consist of redundant loose skin, pre-and post-natal growth deficiency, mental retardation, large fontanels, and dislocation of the hips. The authors present the case of a female patient with involved internal organ disorder and delay in growth in addition to skin laxity in which gene sequence analysis of PYCR1 indicated C.797G>A mutation.

  6. Congenital Cutis Laxa Type 2 Associated With Recurrent Aspiration Pneumonia and Growth Delay: Case Report

    PubMed Central

    Rahmati, Mohammadbagher; Yazdanparast, Maryam; Jahanshahi, Keramatallah; Zakeri, Mohadese

    2015-01-01

    Cutis laxa is a connective tissue disorder caused by deficiency of fibro elastic plexus, which can involve multiple organs. It is inherited in autosomal dominant, autosomal recessive, and X-linked. Autosomal recessive cutis laxa type 2, which appears to compromise a spectrum of disorders, starts with severe wrinkly skin syndrome and leads to more severe diseases related to growth and developmental delays and skeletal anomalies. The clinical manifestations in some of cases of Cutis laxa consist of redundant loose skin, pre-and post-natal growth deficiency, mental retardation, large fontanels, and dislocation of the hips. The authors present the case of a female patient with involved internal organ disorder and delay in growth in addition to skin laxity in which gene sequence analysis of PYCR1 indicated C.797G>A mutation. PMID:26516448

  7. Rare cases of congenital arthrogryposis multiplex caused by novel recurrent CHRNG mutations.

    PubMed

    Seo, Jieun; Choi, In-Ho; Lee, Je Sang; Yoo, Yongjin; Kim, Nayoung K D; Choi, Murim; Ko, Jung Min; Shin, Yong Beom

    2015-04-01

    Multiple pterygium syndrome (MPS) is an autosomal recessively inherited condition that becomes evident before birth, with pterygium at multiple joints and akinesia. There are two forms of this syndrome that are differentiated by clinical severity: the milder form, Escobar type (OMIM#265000), and the more severe form, lethal type (OMIM#253290). Mutations in CHRNG, which encode the acetylcholine receptor gamma subunit, cause most cases of MPS. Here, we present three patients from two unrelated families showing multiple joint contractures in both the upper and lower limbs. High-arched palates with malocclusion, short neck and micrognathia were observed in all patients. Peripheral blood karyotypes were normal. Whole-exome sequencing analysis of the patients' genomes led to the discovery of identical missense (p.Pro143Arg) and frameshift deletion variants (p.Pro251fs*45) on CHRNG. These were rare cases of congenital arthrogryposis multiplex related to novel recessive CHRNG variants in two Korean kindred without apparent relatedness.

  8. Genetics Home Reference: autosomal recessive congenital stationary night blindness

    MedlinePlus

    ... stationary night blindness autosomal recessive congenital stationary night blindness Printable PDF Open All Close All Enable Javascript ... collapse boxes. Description Autosomal recessive congenital stationary night blindness is a disorder of the retina , which is ...

  9. Inheritance patterns and stability of DNA methylation variation in maize near-isogenic lines.

    PubMed

    Li, Qing; Eichten, Steven R; Hermanson, Peter J; Springer, Nathan M

    2014-03-01

    DNA methylation is a chromatin modification that contributes to epigenetic regulation of gene expression. The inheritance patterns and trans-generational stability of 962 differentially methylated regions (DMRs) were assessed in a panel of 71 near-isogenic lines (NILs) derived from maize (Zea mays) inbred lines B73 and Mo17. The majority of DMRs exhibit inheritance patterns that would be expected for local (cis) inheritance of DNA methylation variation such that DNA methylation level was coupled to local genotype. There are few examples of DNA methylation that exhibit trans-acting control or paramutation-like patterns. The cis-inherited DMRs provide an opportunity to study the stability of inheritance for DNA methylation variation. There was very little evidence for alterations of DNA methylation levels at these DMRs during the generations of the NIL population development. DNA methylation level was associated with local genotypes in nearly all of the >30,000 potential cases of inheritance. The majority of the DMRs were not associated with small RNAs. Together, our results suggest that a significant portion of DNA methylation variation in maize exhibits locally (cis) inherited patterns, is highly stable, and does not require active programming by small RNAs for maintenance. DNA methylation may contribute to heritable epigenetic information in many eukaryotic genomes. In this study, we have documented the inheritance patterns and trans-generational stability for nearly 1000 DNA methylation variants in a segregating maize population. At most loci studied, the DNA methylation differences are locally inherited and are not influenced by the other allele or other genomic regions. The inheritance of DNA methylation levels across generations is quite robust with almost no examples of unstable inheritance, suggesting that DNA methylation differences can be quite stably inherited, even in segregating populations.

  10. INHERITED NEUROPATHIES: CLINICAL OVERVIEW AND UPDATE

    PubMed Central

    KLEIN, CHRISTOPHER J.; DUAN, XIAOHUI; SHY, MICHAEL E.

    2014-01-01

    Inherited neuropathy is a group of common neurologic disorders with heterogeneous clinical presentations and genetic causes. Detailed neuromuscular evaluations, including nerve conduction studies, laboratory testing, and histopathologic examination, can assist in identification of the inherited component beyond family history. Genetic testing increasingly enables definitive diagnosis of specific inherited neuropathies. Diagnosis, however, is often complex, and neurologic disability may have both genetic and acquired components in individual patients. The decision of which genetic test to order or whether to order genetic tests is often complicated, and the strategies to maximize the value of testing are evolving. Apart from rare inherited metabolic neuropathies, treatment approaches remain largely supportive. We provide a clinical update of the various types of inherited neuropathies, their differential diagnoses, and distinguishing clinical features (where available). A framework is provided for clinical evaluations, including the inheritance assessment, electrophysiologic examinations, and specific genetic tests. PMID:23801417

  11. Inherited neuropathies: clinical overview and update.

    PubMed

    Klein, Christopher J; Duan, Xiaohui; Shy, Michael E

    2013-10-01

    Inherited neuropathy is a group of common neurologic disorders with heterogeneous clinical presentations and genetic causes. Detailed neuromuscular evaluations, including nerve conduction studies, laboratory testing, and histopathologic examination, can assist in identification of the inherited component beyond family history. Genetic testing increasingly enables definitive diagnosis of specific inherited neuropathies. Diagnosis, however, is often complex, and neurologic disability may have both genetic and acquired components in individual patients. The decision of which genetic test to order or whether to order genetic tests is often complicated, and the strategies to maximize the value of testing are evolving. Apart from rare inherited metabolic neuropathies, treatment approaches remain largely supportive. We provide a clinical update of the various types of inherited neuropathies, their differential diagnoses, and distinguishing clinical features (where available). A framework is provided for clinical evaluations, including the inheritance assessment, electrophysiologic examinations, and specific genetic tests. Copyright © 2013 Wiley Periodicals, Inc.

  12. Age at onset in Huntington's disease: effect of line of inheritance and patient's sex.

    PubMed Central

    Roos, R A; Vegter-van der Vlis, M; Hermans, J; Elshove, H M; Moll, A C; van de Kamp, J J; Bruyn, G W

    1991-01-01

    The Leiden Roster for Huntington's disease (HD) contained data on 2617 cases up to July 1988. The age at onset (AO) was known in 1084 cases and in 1020 of these both their AO and the sex of the affected parent was known. The mean AO was higher for females than for males and higher for maternal than for paternal cases. However, in the group born before 1925 only females with maternal inheritance had a higher mean AO. Data on influence of sex and line of inheritance were present for the grandparents as well as for the great grandparents. Influence of the line of inheritance from the grandparents was particularly present for the grandmother-father (MP) lineage; regarding the great grandparents a significant difference was found between the MPM and PMP lineage. The results obtained for juvenile HD cases were comparable to those previously published. In late onset cases (over 50 years) no maternal preponderance in inheritance was found. PMID:1833547

  13. Infantile variant of Bartter syndrome and sensorineural deafness: A new autosomal recessive disorder

    SciTech Connect

    Landau, D.; Shalev, H.; Carmi, Rivka; Ohaly, M.

    1995-12-04

    The infantile variant of Bartter syndrome (IBS) is usually associated with maternal polyhydramnios, premature birth, postnatal polyuria and hypokalemic hypochloremic metabolic alkalosis and a typical appearance. IBS is thought to be an autosomal recessive trait. Several congenital tubular defects are associated with sensorineural deafness (SND). However, an association between the IBS and SND has not been reported so far. Here we describe 5 children of an extended consanguineous Bedouin family with IBS and SND. In 3 of the cases, the typical electrolyte imbalance and facial appearance were detected neonatally. SND was detected as early as age 1 month, suggesting either coincidental homozygotization of 2 recessive genes or a pleiotropic effect of one autosomal recessive gene. This association suggests that evaluation of SND is warranted in every case of IBS. 35 refs., 2 figs., 2 tabs.

  14. [The congenital afibrinogenemia: case report].

    PubMed

    Brahem, Imen; Charfeddine, Bassem; Chraiti, Haythem; Ben Abdallah, Jihene; Ben Othmen, Leila; Neffati, Souhir; Ali Smach, Mohamed; Ltaief, Affef; Ksourri, Monia; Dridi, Hedi; Limem, Khalifa

    2010-01-01

    The deficiency in factor I or fibrinogen is a largely unknown genetic disease. It is a rare condition inherited as an autosomal recessive, whose clinical events are variable, ranging from moderate to minimal bleeding or cataclysmic hemorrhage. We report a case of congenital afibrinogenemia in a 17 years-old patient hospitalized in surgical ICU for hemoperitoneum medium abundance discovered by abdominal ultrasound performed before a picture of abdominopelvic pain lasting for 24 hours. Exploration led to the diagnosis of congenital afibrinogenemia with favorable evolution with a contribution of factor deficient. Through this case we raise the problem of congenital afibrinogenemia in diagnosis and the peculiarities of its management.

  15. Inheritance of Febrile Seizures in Sudden Unexplained Death in Toddlers

    PubMed Central

    Holm, Ingrid A.; Poduri, Annapurna; Crandall, Laura; Haas, Elisabeth; Grafe, Marjorie R.; Kinney, Hannah C.; Krous, Henry F.

    2014-01-01

    Sudden unexplained death in toddlers has been associated with febrile seizures, family history of febrile seizures, and hippocampal anomalies. We investigated the mode of inheritance for febrile seizures in these families. A three-generation pedigree was obtained from families enrolled in the San Diego Sudden Unexplained Death in Childhood Research Project, involving toddlers with sudden unexplained death, febrile seizures, and family history of febrile seizures. In our six cases, death was unwitnessed and related to sleep. The interval from last witnessed febrile seizure to death ranged from 3 weeks to 6 months. Hippocampal abnormalities were identified in one of three cases with available autopsy sections. Autosomal dominant inheritance of febrile seizures was observed in three families. A fourth demonstrated autosomal dominant inheritance with incomplete penetrance or variable expressivity. In two families, the maternal and paternal sides manifested febrile seizures. In this series, the major pattern of inheritance in toddlers with sudden unexplained death and febrile seizures was autosomal dominant. Future studies should develop markers (including genetic) to identify which patients with febrile seizures are at risk for sudden unexplained death in childhood, and to provide guidance for families and physicians. PMID:22490769

  16. [Familiar case of granular dystrophy and oculocutaneous albinism].

    PubMed

    Gómez-Valcárcel, M; Ching-Wong, J L; Alvarez-Verduzco, O; Niño-Pecina, A; Villanueva-Mendoza, C

    2006-05-01

    A 35-year-old female patient with blurred vision since childhood, for which no treatment had been given, presented with poor visual acuity. She had white skin and fair yellow hair. There were several well circumscribed deposits in the central and anterior corneal stroma, and iris transillumination and foveal hypoplasia were evident. The clinical diagnosis was oculo-cutaneous albinism and granular corneal dystrophy. We found oculo-cutaneous albinism in two brothers and granular dystrophy in three brothers, the mother and a son. Corneal dystrophy is an autosomal dominant disorder inherited independently of oculocutaneous albinism, which is inherited as an autosomal recessive condition. This is the first case report of granular dystrophy concurrent with oculocutaneous albinism.

  17. A nuclear Argonaute promotes multigenerational epigenetic inheritance and germline immortality.

    PubMed

    Buckley, Bethany A; Burkhart, Kirk B; Gu, Sam Guoping; Spracklin, George; Kershner, Aaron; Fritz, Heidi; Kimble, Judith; Fire, Andrew; Kennedy, Scott

    2012-09-20

    Epigenetic information is frequently erased near the start of each new generation. In some cases, however, epigenetic information can be transmitted from parent to progeny (multigenerational epigenetic inheritance). A particularly notable example of this type of epigenetic inheritance is double-stranded RNA-mediated gene silencing in Caenorhabditis elegans. This RNA-mediated interference (RNAi) can be inherited for more than five generations. To understand this process, here we conduct a genetic screen for nematodes defective in transmitting RNAi silencing signals to future generations. This screen identified the heritable RNAi defective 1 (hrde-1) gene. hrde-1 encodes an Argonaute protein that associates with small interfering RNAs in the germ cells of progeny of animals exposed to double-stranded RNA. In the nuclei of these germ cells, HRDE-1 engages the nuclear RNAi defective pathway to direct the trimethylation of histone H3 at Lys 9 (H3K9me3) at RNAi-targeted genomic loci and promote RNAi inheritance. Under normal growth conditions, HRDE-1 associates with endogenously expressed short interfering RNAs, which direct nuclear gene silencing in germ cells. In hrde-1- or nuclear RNAi-deficient animals, germline silencing is lost over generational time. Concurrently, these animals exhibit steadily worsening defects in gamete formation and function that ultimately lead to sterility. These results establish that the Argonaute protein HRDE-1 directs gene-silencing events in germ-cell nuclei that drive multigenerational RNAi inheritance and promote immortality of the germ-cell lineage. We propose that C. elegans use the RNAi inheritance machinery to transmit epigenetic information, accrued by past generations, into future generations to regulate important biological processes.

  18. Power law for the duration of recession and prosperity in Latin American countries

    NASA Astrophysics Data System (ADS)

    Redelico, Francisco O.; Proto, Araceli N.; Ausloos, Marcel

    2008-11-01

    Ormerod and Mounfield [P. Ormerod, C. Mounfield, Power law distribution of duration and magnitude of recessions in capitalist economies: Breakdown of scaling, Physica A 293 (2001) 573] and Ausloos et al. [M. Ausloos, J. Mikiewicz, M. Sanglier, The durations of recession and prosperity: Does their distribution follow a power or an exponential law? Physica A 339 (2004) 548] have independently analyzed the duration of recessions for developed countries through the evolution of the GDP in different time windows. It was found that there is a power law governing the duration distribution. We have analyzed data collected from 19 Latin American countries in order to observe whether such results are valid or not for developing countries. The case of prosperity years is also discussed. We observe that the power law of recession time intervals, see Ref. [1], is valid for Latin American countries as well. Thus an interesting point is discovered: the same scaling time is found in the case of recessions for the three data sets (ca. 1 year), and this could represent a universal feature. Other time scale parameters differ significantly from each other.

  19. A recessive genetic model and runs of homozygosity in major depressive disorder

    PubMed Central

    Power, Robert A.; Keller, Matthew C.; Ripke, Stephan; Abdellaoui, Abdel; Wray, Naomi R.; Sullivan, Patrick F; Breen, Gerome

    2014-01-01

    Genome-wide association studies (GWASs) of major depressive disorder (MDD) have yet to identify variants that surpass the threshold for genome-wide significance. A recent study reported that runs of homozygosity (ROH) are associated with schizophrenia, reflecting a novel genetic risk factor resulting from increased parental relatedness and recessive genetic effects. Here we undertake an analysis of ROH for MDD using the 9,238 MDD cases and 9,521 controls reported in a recent mega-analysis of 9 GWAS. Since evidence for association with ROH could reflect a recessive mode of action at loci, we also conducted a genome-wide association analyses under a recessive model. The genome-wide association analysis using a recessive model found no significant associations. Our analysis of ROH suggested that there was significant heterogeneity of effect across studies in effect (p=0.001), and it was associated with genotyping platform and country of origin. The results of the ROH analysis show that differences across studies can lead to conflicting systematic genome-wide differences between cases and controls that are unaccounted for by traditional covariates. They highlight the sensitivity of the ROH method to spurious associations, and the need to carefully control for potential confounds in such analyses. We found no strong evidence for a recessive model underlying MDD. PMID:24482242

  20. Time to Play: Recognizing the Benefits of Recess

    ERIC Educational Resources Information Center

    Ramstetter, Catherine; Murray, Robert

    2017-01-01

    Given the evidence of the value of recess for children and teachers, what can educators, schools, and districts do to promote this critical aspect of the education of the whole child? Daily decisions about who gets recess and when and where it will happen are often made by teachers; thus, teachers are a crucial link for recess. Policies that…

  1. Calcium Ions in Inherited Cardiomyopathies.

    PubMed

    Deftereos, Spyridon; Papoutsidakis, Nikolaos; Giannopoulos, Georgios; Angelidis, Christos; Raisakis, Konstantinos; Bouras, Georgios; Davlouros, Periklis; Panagopoulou, Vasiliki; Goudevenos, John; Cleman, Michael W; Lekakis, John

    2016-01-01

    Inherited cardiomyopathies are a known cause of heart failure, although the pathways and mechanisms leading from mutation to the heart failure phenotype have not been elucidated. There is strong evidence that this transition is mediated, at least in part, by abnormal intracellular Ca(2+) handling, a key ion in ventricular excitation, contraction and relaxation. Studies in human myocytes, animal models and in vitro reconstituted contractile protein complexes have shown consistent correlations between Ca(2+) sensitivity and cardiomyopathy phenotype, irrespective of the causal mutation. In this review we present the available data about the connection between mutations linked to familial hypertrophic (HCM), dilated (DCM) and restrictive (RCM) cardiomyopathy, right ventricular arrhythmogenic cardiomyopathy/dysplasia (ARVC/D) as well as left ventricular non-compaction and the increase or decrease in Ca(2+) sensitivity, together with the results of attempts to reverse the manifestation of heart failure by manipulating Ca(2+) homeostasis.

  2. Semiconductor structure and recess formation etch technique

    DOEpatents

    Lu, Bin; Sun, Min; Palacios, Tomas Apostol

    2017-02-14

    A semiconductor structure has a first layer that includes a first semiconductor material and a second layer that includes a second semiconductor material. The first semiconductor material is selectively etchable over the second semiconductor material using a first etching process. The first layer is disposed over the second layer. A recess is disposed at least in the first layer. Also described is a method of forming a semiconductor structure that includes a recess. The method includes etching a region in a first layer using a first etching process. The first layer includes a first semiconductor material. The first etching process stops at a second layer beneath the first layer. The second layer includes a second semiconductor material.

  3. Inherited Determinants of Ovarian Cancer Survival

    PubMed Central

    Goode, Ellen L.; Maurer, Matthew J.; Sellers, Thomas A.; Phelan, Catherine M.; Kalli, Kimberly R.; Fridley, Brooke L.; Vierkant, Robert A.; Armasu, Sebastian M.; White, Kristin L.; Keeney, Gary L.; Cliby, William A.; Rider, David N.; Kelemen, Linda E.; Jones, Monica B.; Peethambaram, Prema P.; Lancaster, Johnathan M.; Olson, Janet E.; Schildkraut, Joellen M.; Cunningham, Julie M.; Hartmann, Lynn C.

    2010-01-01

    Purpose Due to variation of outcome among cases, we sought to examine whether overall survival in ovarian cancer was associated with common inherited variants in 227 candidate genes from ovarian cancer-related pathways including angiogenesis, inflammation, detoxification, glycosylation, one-carbon transfer, apoptosis, cell cycle regulation, and cellular senescence. Experimental Design Blood samples were obtained from 325 women with invasive epithelial ovarian cancer diagnosed at the Mayo Clinic from 1999 to 2006. During a median follow-up of 3.8 years (range, 0.1 – 8.6 years), 157 deaths were observed. Germline DNA was analyzed at 1,416 single nucleotide polymorphisms (SNPs). For all patients, and for 203 with serous subtype, we assessed the overall significance of each gene and pathway, and estimated risk of death via hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for known prognostic factors. Results Variation within angiogenesis was most strongly associated with survival time overall (p=0.03) and among patients with serous cancer (p=0.05), particularly for EIF2B5 rs4912474 (all patients HR 0.69, 95% CI 0.54-0.89, p=0.004), VEGFC rs17697305 (serous subtype HR 2.29, 95% CI 1.34-3.92, p=0.003), and four SNPs in VHL. Variation within the inflammation pathway was borderline significant (all patients, p=0.09), and SNPs in CCR3, IL1B, IL18, CCL2, and ALOX5 which correlated with survival time are worthy of follow-up. Conclusion An extensive multiple-pathway assessment found evidence that inherited differences may play a role in outcome of ovarian cancer patients, particularly in genes within the angiogenesis and inflammation pathways. Our work supports efforts to target such mediators for therapeutic gain. PMID:20103664

  4. Semiconductor devices having a recessed electrode structure

    DOEpatents

    Palacios, Tomas Apostol; Lu, Bin; Matioli, Elison de Nazareth

    2015-05-26

    An electrode structure is described in which conductive regions are recessed into a semiconductor region. Trenches may be formed in a semiconductor region, such that conductive regions can be formed in the trenches. The electrode structure may be used in semiconductor devices such as field effect transistors or diodes. Nitride-based power semiconductor devices are described including such an electrode structure, which can reduce leakage current and otherwise improve performance.

  5. Posterior peritoneal recesses: assessment using CT

    SciTech Connect

    Rubenstein, W.A.; Auh, Y.H.; Zirinsky, K.; Kneeland, J.B.; Whalen, J.P.; Kazam, E.

    1985-08-01

    Intraperitoneal compartments may extend posteriorly to the level of known retroperitoneal structures at several locations within the abdomen. These locations include the posterior subhepatic or hepatorenal space, the splenorenal space, the retropancreatic recess, the paracolic gutters, and the pararectal fossae. Because of their posterior location, fluid collections within these compartments may be mistaken radiologically for retroperitoneal masses. The sectional anatomy of these spaces and particularly their appearance on computed tomographic scans, are illustrated in this paper.

  6. Recession trims third-quarter building costs

    SciTech Connect

    Morgan, J.M.

    1983-05-09

    The composite cost index for building oil pipelines during the third quarter of 1982 showed a decrease of 0.96%. This decrease was due to a steady drop in the rate of inflation for most pipeline construction materials during the first 9 months of the year. The major thrust behind the pipeline materials decline was a sharp 5.3% drop in the average price of steel line pipe. However, the pipeline construction recession has failed to deter escalating pipeline labor rates.

  7. Cutting Symmetrical Recesses In Soft Ceramic Tiles

    NASA Technical Reports Server (NTRS)

    Nesotas, Tony C.; Tyler, Brent

    1989-01-01

    Simple tool cuts hemispherical recesses in soft ceramic tiles. Designed to expose wires of thermocouples embedded in tiles without damaging leads. Creates neat, precise holes around wires. End mill includes axial hole to accommodate thermocouple wires embedded in material to be cut. Wires pass into hole without being bent or broken. Dimensions in inches. Used in place of such tools as dental picks, tweezers, spatulas, and putty knives.

  8. Cutting Symmetrical Recesses In Soft Ceramic Tiles

    NASA Technical Reports Server (NTRS)

    Nesotas, Tony C.; Tyler, Brent

    1989-01-01

    Simple tool cuts hemispherical recesses in soft ceramic tiles. Designed to expose wires of thermocouples embedded in tiles without damaging leads. Creates neat, precise holes around wires. End mill includes axial hole to accommodate thermocouple wires embedded in material to be cut. Wires pass into hole without being bent or broken. Dimensions in inches. Used in place of such tools as dental picks, tweezers, spatulas, and putty knives.

  9. [The inheritance of an ultra-dwarf plant mutant from upland cotton].

    PubMed

    Chen, Xu-Sheng; DI, Jia-Chun; Xu, Nai-Yin; Xiao, Song-Hua; Liu, Jian-Guang

    2007-04-01

    The inheritance of an ultra-dwarf plant mutant from upland cotton (Gossypium hirsutum L.) was studied, which showed that the mutant was controlled by single recessive quality gene. This gene was denominated as du tentatively. No similar mutant has been found in upland cotton. The mutation could not normally flower and produce bolls under natural conditions, and its mature height was only 10.5 cm. When treated with exogenous GA3, it could normally flower and boll, and plant height could reach 57.8 cm finally.

  10. Inheritance of ear wax types, ear lobe attachment and tongue rolling ability.

    PubMed

    Cruz-Gonzalez, L; Lisker, R

    1982-01-01

    The mode of inheritance of ear wax type, ear lobe attachment and tongue rolling ability were studied in 77 families with a total of 293 children. The results clearly showed that the dry ear wax type and the attached ear lobe type represent the homozygous state for two pairs of autosomal recessive genes. The evidence for the same being true regarding the lack of ability to roll the tongue was less conclusive in our material, but this could be due to difficulties in communication between the examined individuals and the examiners.

  11. Thiamine responsive megaloblastic anemia syndrome associated with patent ductus arteriosus: First case report from Kashmir Valley of the Indian subcontinent

    PubMed Central

    Ganie, Mohd Ashraf; Ali, Imran; Ahangar, A. G.; Wani, Mohd Maqbool; Ahmed, Sanjeed; Bhat, Manzoor Ahmed; Seth, Sulaiman; Mudasir, Syed

    2012-01-01

    Thiamine responsive megaloblastic anemia syndrome, an autosomal recessive inherited disorder characterized by a triad of anemia, diabetes mellitus and sensorineural deafness is caused by a deficiency of a thiamine transporter protein. The disorder is rare and has not been reported from our community which has high background of consanguinity. We report a six years old girl who presented with diabetes mellitus which remitted after thiamine replacement. The girl in addition had sensorineural deafness, reinopathy, atrial septal defect and megaloblastic anemia which responded to high doses of thymine. This is the first case reported from Kashmir valley and third from India. The presentation and management in such cases is discussed. PMID:22837935

  12. Thiamine responsive megaloblastic anemia syndrome associated with patent ductus arteriosus: First case report from Kashmir Valley of the Indian subcontinent.

    PubMed

    Ganie, Mohd Ashraf; Ali, Imran; Ahangar, A G; Wani, Mohd Maqbool; Ahmed, Sanjeed; Bhat, Manzoor Ahmed; Seth, Sulaiman; Mudasir, Syed

    2012-07-01

    Thiamine responsive megaloblastic anemia syndrome, an autosomal recessive inherited disorder characterized by a triad of anemia, diabetes mellitus and sensorineural deafness is caused by a deficiency of a thiamine transporter protein. The disorder is rare and has not been reported from our community which has high background of consanguinity. We report a six years old girl who presented with diabetes mellitus which remitted after thiamine replacement. The girl in addition had sensorineural deafness, reinopathy, atrial septal defect and megaloblastic anemia which responded to high doses of thymine. This is the first case reported from Kashmir valley and third from India. The presentation and management in such cases is discussed.

  13. The Great Recession, unemployment and suicide

    PubMed Central

    Norström, Thor; Grönqvist, Hans

    2015-01-01

    Background How have suicide rates responded to the marked increase in unemployment spurred by the Great Recession? Our paper puts this issue into a wider perspective by assessing (1) whether the unemployment-suicide link is modified by the degree of unemployment protection, and (2) whether the effect on suicide of the present crisis differs from the effects of previous economic downturns. Methods We analysed the unemployment-suicide link using time-series data for 30 countries spanning the period 1960–2012. Separate fixed-effects models were estimated for each of five welfare state regimes with different levels of unemployment protection (Eastern, Southern, Anglo-Saxon, Bismarckian and Scandinavian). We included an interaction term to capture the possible excess effect of unemployment during the Great Recession. Results The largest unemployment increases occurred in the welfare state regimes with the least generous unemployment protection. The unemployment effect on male suicides was statistically significant in all welfare regimes, except the Scandinavian one. The effect on female suicides was significant only in the eastern European country group. There was a significant gradient in the effects, being stronger the less generous the unemployment protection. The interaction term capturing the possible excess effect of unemployment during the financial crisis was not significant. Conclusions Our findings suggest that the more generous the unemployment protection the weaker the detrimental impact on suicide of the increasing unemployment during the Great Recession. PMID:25339416

  14. Etiology and occurrence of gingival recession - An epidemiological study

    PubMed Central

    Mythri, Sarpangala; Arunkumar, Suryanarayan Maiya; Hegde, Shashikanth; Rajesh, Shanker Kashyap; Munaz, Mohamed; Ashwin, Devasya

    2015-01-01

    Objectives: Gingival recession is the term used to characterize the apical shift of the marginal gingiva from its normal position on the crown of the tooth. It is frequently observed in adult subjects. The occurrence and severity of the gingival recession present considerable differences between populations. To prevent gingival recession from occurring, it is essential to detect the underlying etiology. The aim of the present study was to determine the occurrence of gingival recession and to identify the most common factor associated with the cause of gingival recession. Methods: A total of 710 subjects aged between 15 years to 60 years were selected. Data were collected by an interview with the help of a proforma and then the dental examination was carried out. The presence of gingival recession was recorded using Miller's classification of gingival recession. The Silness and Loe Plaque Index, Loe and Silness gingival index, community periodontal index were recorded. The data thus obtained were subjected to statistical analysis using Chi-square test and Student's unpaired t-test. Results: Of 710 subjects examined, 291 (40.98%) subjects exhibited gingival recession. The frequency of gingival recession was found to increase with age. High frequency of gingival recession was seen in males (60.5%) compared to females (39.5%). Gingival recession was commonly seen in mandibular incisors (43.0%). Miller's class I gingival recession was more commonly seen. The most common cause for gingival recession was dental plaque accumulation (44.1%) followed by faulty toothbrushing (42.7%). Conclusion: Approximately half of the subjects examined exhibited gingival recession. The etiology of gingival recession is multifactorial, and its appearance is always the result of more than one factor acting together. PMID:26941519

  15. Glycine substitutions in the triple-helical region of type VII collagen result in a spectrum of dystrophic epidermolysis bullosa phenotypes and patterns of inheritance

    SciTech Connect

    Christiano, A.M.; McGrath, J.A.; Uitto, J.; Kong Chong Tan

    1996-04-01

    The dystrophic forms of epidermolysis bullosa (DEB) are characterized by fragility of the skin and mucous membranes. DEB can be inherited in either an autosomal dominant or autosomal recessive pattern, and the spectrum of clinical severity is highly variable. The unifying diagnostic hallmark of DEB is abnormalities in the anchoring fibrils, which consist of type VII collagen, and recently, mutations in the corresponding gene, COL7A1, have been disclosed in a number of families. In this study, we report six families with glycine substitution mutations in the triple-helical region of type VII collagen. Among the six families, two demonstrated a mild phenotype, and the inheritance of the mutation was consistent with the dominantly inherited form of DEB. In the four other families, the mutation was silent in the heterozygous state but, when present in the homozygous state, or combined with a second mutation, resulted in a recessively inherited DEB phenotype. Type VII collagen is, therefore, unique among the collagen genes, in that different glycine substitutions can be either silent in heterozygous individuals or result in a dominantly inherited DEB. Inspection of the locations of the glycine substitutions along the COL7A1 polypeptide suggests that the consequences of these mutations, in terms of phenotype and pattern of inheritance, are position independent. 29 refs., 4 figs., 2 tabs.

  16. Infantile onset spinocerebellar ataxia caused by compound heterozygosity for Twinkle mutations and modeling of Twinkle mutations causing recessive disease

    PubMed Central

    Gulsuner, Suleyman; Stapleton, Gail A.; Walsh, Tom; Lee, Ming K.; Mandell, Jessica B.; Morales, Augusto; Klevit, Rachel E.; King, Mary-Claire; Rogers, R. Curtis

    2016-01-01

    Mutations in nuclear genes required for the replication and maintenance of mitochondrial DNA cause progressive multisystemic neuromuscular disorders with overlapping phenotypes. Biallelic mutations in C10orf2, encoding the Twinkle mitochondrial DNA helicase, lead to infantile-onset cerebellar ataxia (IOSCA), as well as milder and more severe phenotypes. We present a 13-year-old girl with ataxia, severe hearing loss, optic atrophy, peripheral neuropathy, and hypergonadotropic hypogonadism. Whole-exome sequencing revealed that the patient is compound heterozygous for previously unreported variants in the C10orf2 gene: a paternally inherited frameshift variant (c.333delT; p.L112Sfs*3) and a maternally inherited missense variant (c.904C>T; p.R302W). The identification of novel C10orf2 mutations extends the spectrum of mutations in the Twinkle helicase causing recessive disease, in particular the intermediate IOSCA phenotype. Structural modeling suggests that the p.R302W mutation and many other recessively inherited Twinkle mutations impact the position or interactions of the linker region, which is critical for the oligomeric ring structure and activity of the helicase. This study emphasizes the utility of whole-exome sequencing for the genetic diagnosis of a complex multisystemic disorder. PMID:27551684

  17. Mutations in c10orf11, a melanocyte-differentiation gene, cause autosomal-recessive albinism.

    PubMed

    Grønskov, Karen; Dooley, Christopher M; Østergaard, Elsebet; Kelsh, Robert N; Hansen, Lars; Levesque, Mitchell P; Vilhelmsen, Kaj; Møllgård, Kjeld; Stemple, Derek L; Rosenberg, Thomas

    2013-03-07

    Autosomal-recessive albinism is a hypopigmentation disorder with a broad phenotypic range. A substantial fraction of individuals with albinism remain genetically unresolved, and it has been hypothesized that more genes are to be identified. By using homozygosity mapping of an inbred Faroese family, we identified a 3.5 Mb homozygous region (10q22.2-q22.3) on chromosome 10. The region contains five protein-coding genes, and sequencing of one of these, C10orf11, revealed a nonsense mutation that segregated with the disease and showed a recessive inheritance pattern. Investigation of additional albinism-affected individuals from the Faroe Islands revealed that five out of eight unrelated affected persons had the nonsense mutation in C10orf11. Screening of a cohort of autosomal-recessive-albinism-affected individuals residing in Denmark showed a homozygous 1 bp duplication in C10orf11 in an individual originating from Lithuania. Immunohistochemistry showed localization of C10orf11 in melanoblasts and melanocytes in human fetal tissue, but no localization was seen in retinal pigment epithelial cells. Knockdown of the zebrafish (Danio rerio) homolog with the use of morpholinos resulted in substantially decreased pigmentation and a reduction of the apparent number of pigmented melanocytes. The morphant phenotype was rescued by wild-type C10orf11, but not by mutant C10orf11. In conclusion, we have identified a melanocyte-differentiation gene, C10orf11, which when mutated causes autosomal-recessive albinism in humans. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  18. Mutations in C10orf11, a Melanocyte-Differentiation Gene, Cause Autosomal-Recessive Albinism

    PubMed Central

    Grønskov, Karen; Dooley, Christopher M.; Østergaard, Elsebet; Kelsh, Robert N.; Hansen, Lars; Levesque, Mitchell P.; Vilhelmsen, Kaj; Møllgård, Kjeld; Stemple, Derek L.; Rosenberg, Thomas

    2013-01-01

    Autosomal-recessive albinism is a hypopigmentation disorder with a broad phenotypic range. A substantial fraction of individuals with albinism remain genetically unresolved, and it has been hypothesized that more genes are to be identified. By using homozygosity mapping of an inbred Faroese family, we identified a 3.5 Mb homozygous region (10q22.2–q22.3) on chromosome 10. The region contains five protein-coding genes, and sequencing of one of these, C10orf11, revealed a nonsense mutation that segregated with the disease and showed a recessive inheritance pattern. Investigation of additional albinism-affected individuals from the Faroe Islands revealed that five out of eight unrelated affected persons had the nonsense mutation in C10orf11. Screening of a cohort of autosomal-recessive-albinism-affected individuals residing in Denmark showed a homozygous 1 bp duplication in C10orf11 in an individual originating from Lithuania. Immunohistochemistry showed localization of C10orf11 in melanoblasts and melanocytes in human fetal tissue, but no localization was seen in retinal pigment epithelial cells. Knockdown of the zebrafish (Danio rerio) homolog with the use of morpholinos resulted in substantially decreased pigmentation and a reduction of the apparent number of pigmented melanocytes. The morphant phenotype was rescued by wild-type C10orf11, but not by mutant C10orf11. In conclusion, we have identified a melanocyte-differentiation gene, C10orf11, which when mutated causes autosomal-recessive albinism in humans. PMID:23395477

  19. Mutations in NGLY1 Cause an Inherited Disorder of the Endoplasmic Reticulum-Associated Degradation (ERAD) Pathway

    PubMed Central

    Enns, Gregory M.; Shashi, Vandana; Bainbridge, Matthew; Gambello, Michael J.; Zahir, Farah R.; Bast, Thomas; Crimian, Rebecca; Schoch, Kelly; Platt, Julia; Cox, Rachel; Bernstein, Jonathan; Scavina, Mena; Walter, Rhonda S.; Bibb, Audrey; Jones, Melanie; Hegde, Madhuri; Graham, Brett H.; Need, Anna C.; Oviedo, Angelica; Schaaf, Christian P.; Boyle, Sean; Butte, Atul J.; Chen, Rong; Clark, Michael J.; Haraksingh, Rajini; Cowan, Tina M.; He, Ping; Langlois, Sylvie; Zoghbi, Huda Y.; Snyder, Michael; Gibbs, Richard; Freeze, Hudson H.; Goldstein, David B.

    2014-01-01

    Purpose The endoplasmic reticulum-associated degradation (ERAD) pathway is responsible for the translocation of misfolded proteins across the ER membrane into the cytosol for subsequent degradation by the proteasome. In order to understand the spectrum of clinical and molecular findings in a complex neurological syndrome, we studied a series of eight patients with inherited deficiency of N-glycanase 1 (NGLY1), a novel disorder of cytosolic ERAD dysfunction. Methods Whole-genome, whole-exome or standard Sanger sequencing techniques were employed. Retrospective chart reviews were performed in order to obtain clinical data. Results All patients had global developmental delay, a movement disorder, and hypotonia. Other common findings included hypo- or alacrima (7/8), elevated liver transaminases (6/7), microcephaly (6/8), diminished reflexes (6/8), hepatocyte cytoplasmic storage material or vacuolization (5/6), and seizures (4/8). The nonsense mutation c.1201A>T (p.R401X) was the most common deleterious allele. Conclusions NGLY1 deficiency is a novel autosomal recessive disorder of the ERAD pathway associated with neurological dysfunction, abnormal tear production, and liver disease. The majority of patients detected to date carry a specific nonsense mutation that appears to be associated with severe disease. The phenotypic spectrum is likely to enlarge as cases with a more broad range of mutations are detected. PMID:24651605

  20. Systematic large-scale study of the inheritance mode of Mendelian disorders provides new insight into human diseasome.

    PubMed

    Hao, Dapeng; Wang, Guangyu; Yin, Zuojing; Li, Chuanxing; Cui, Yan; Zhou, Meng

    2014-11-01

    One important piece of information about the human Mendelian disorders is the mode of inheritance. Recent studies of human genetic diseases on a large scale have provided many novel insights into the underlying molecular mechanisms. However, most successful analyses ignored the mode of inheritance of diseases, which severely limits our understanding of human disease mechanisms relating to the mode of inheritance at the large scale. Therefore, we here conducted a systematic large-scale study of the inheritance mode of Mendelian disorders, to bring new insight into human diseases. Our analyses include the comparison between dominant and recessive disease genes on both genomic and proteomic characteristics, Mendelian mutations, protein network properties and disease connections on both the genetic and the population levels. We found that dominant disease genes are more functionally central, topological central and more sensitive to disease outcome. On the basis of these findings, we suggested that dominant diseases should have higher genetic heterogeneity and should have more comprehensive connections with each other compared with recessive diseases, a prediction we confirm by disease network and disease comorbidity.

  1. Discovery of a potentially deleterious variant in TMEM87B in a patient with a hemizygous 2q13 microdeletion suggests a recessive condition characterized by congenital heart disease and restrictive cardiomyopathy

    PubMed Central

    Coughlin, Curtis R.; Geiger, Elizabeth A.; Salvador, Blake J.; Elias, Ellen R.; Cavanaugh, Jean L.; Chatfield, Kathryn C.; Miyamoto, Shelley D.; Shaikh, Tamim H.

    2016-01-01

    Restrictive cardiomyopathy (RCM) is a rare cause of heart muscle disease with the highest mortality rate among cardiomyopathy types. The etiology of RCM is poorly understood, although genetic causes have been implicated, and syndromic associations have been described. Here, we describe a patient with an atrial septal defect and restrictive cardiomyopathy along with craniofacial anomalies and intellectual disabilities. Initial screening using chromosomal microarray analysis (CMA) identified a maternally inherited 2q13 microdeletion. The patient had many of the features reported in previous cases with the recurrent 2q13 microdeletion syndrome. However, the inheritance of the microdeletion from an unaffected mother combined with the low incidence (10%) and milder forms of cardiac defects in previously reported cases made the clinical significance of the CMA results unclear. Whole-exome sequencing (WES) with trio-based analysis was performed and identified a paternally inherited TMEM87B mutation (c.1366A>G, p.Asn456Asp) in the patient. TMEM87B, a highly conserved, transmembrane protein of currently unknown function, lies within the critical region of the recurrent 2q13 microdeletion syndrome. Furthermore, a recent study had demonstrated that depletion of TMEM87B in zebrafish embryos affected cardiac development and led to cardiac hypoplasia. Thus, by combining CMA and WES, we potentially uncover an autosomal-recessive disorder characterized by a severe cardiac phenotype caused by mutations in TMEM87B. This study expands the spectrum of phenotypes associated with the recurrent 2q13 microdeletion syndrome and also further suggests the role of TMEM87B in its etiology, especially the cardiac pathology. PMID:27148590

  2. Method and Excel VBA Algorithm for Modeling Master Recession Curve Using Trigonometry Approach.

    PubMed

    Posavec, Kristijan; Giacopetti, Marco; Materazzi, Marco; Birk, Steffen

    2017-06-26

    A new method was developed and implemented into an Excel Visual Basic for Applications (VBAs) algorithm utilizing trigonometry laws in an innovative way to overlap recession segments of time series and create master recession curves (MRCs). Based on a trigonometry approach, the algorithm horizontally translates succeeding recession segments of time series, placing their vertex, that is, the highest recorded value of each recession segment, directly onto the appropriate connection line defined by measurement points of a preceding recession segment. The new method and algorithm continues the development of methods and algorithms for the generation of MRC, where the first published method was based on a multiple linear/nonlinear regression model approach (Posavec et al. ). The newly developed trigonometry-based method was tested on real case study examples and compared with the previously published multiple linear/nonlinear regression model-based method. The results show that in some cases, that is, for some time series, the trigonometry-based method creates narrower overlaps of the recession segments, resulting in higher coefficients of determination R(2) , while in other cases the multiple linear/nonlinear regression model-based method remains superior. The Excel VBA algorithm for modeling MRC using the trigonometry approach is implemented into a spreadsheet tool (MRCTools v3.0 written by and available from Kristijan Posavec, Zagreb, Croatia) containing the previously published VBA algorithms for MRC generation and separation. All algorithms within the MRCTools v3.0 are open access and available free of charge, supporting the idea of running science on available, open, and free of charge software. © 2017, National Ground Water Association.

  3. Impact of the 2008 Global Recession on air quality over the United States: Implications for surface ozone levels from changes in NOx emissions

    NASA Astrophysics Data System (ADS)

    Tong, Daniel; Pan, Li; Chen, Weiwei; Lamsal, Lok; Lee, Pius; Tang, Youhua; Kim, Hyuncheol; Kondragunta, Shobha; Stajner, Ivanka

    2016-09-01

    Satellite and ground observations detected large variability in nitrogen oxides (NOx) during the 2008 economic recession, but the impact of the recession on air quality has not been quantified. This study combines observed NOx trends and a regional chemical transport model to quantify the impact of the recession on surface ozone (O3) levels over the continental United States. The impact is quantified by simulating O3 concentrations under two emission scenarios: business-as-usual (BAU) and recession. In the BAU case, the emission projection from the Cross-State Air Pollution Rule is used to estimate the "would-be" NOx emission level in 2011. In the recession case, the actual NO2 trends observed from Air Quality System ground monitors and the Ozone Monitoring Instrument on the Aura satellite are used to obtain "realistic" changes in NOx emissions. The model prediction with the recession effect agrees better with ground O3 observations over time and space than the prediction with the BAU emission. The results show that the recession caused a 1-2 ppbv decrease in surface O3 concentration over the eastern United States, a slight increase (0.5-1 ppbv) over the Rocky Mountain region, and mixed changes in the Pacific West. The gain in air quality benefits during the recession, however, could be quickly offset by the much slower emission reduction rate during the post-recession period.

  4. Impact of the 2008 Global Recession on Air Quality over the United States: Implications for Surface Ozone Levels from Changes in NOx Emissions

    NASA Technical Reports Server (NTRS)

    Tong, Daniel; Pan, Li; Chen, Weiwei; Lamsal, Lok; Lee, Pius; Tang, Youhua; Kim, Hyuncheol; Kondragunta, Shobha; Stajner, Ivanka

    2016-01-01

    Satellite and ground observations detected large variability in nitrogen oxides (NOx) during the 2008 economic recession, but the impact of the recession on air quality has not been quantified. This study combines observed NOx trends and a regional chemical transport model to quantify the impact of the recession on surface ozone (O3) levels over the continental United States. The impact is quantified by simulating O3 concentrations under two emission scenarios: business-as-usual (BAU) and recession. In the BAU case, the emission projection from the Cross-State Air Pollution Rule is used to estimate the would-be NOx emission level in 2011. In the recession case, the actual NO2 trends observed from Air Quality System ground monitors and the Ozone Monitoring Instrument on the Aura satellite are used to obtain realistic changes in NOx emissions. The model prediction with the recession effect agrees better with ground O3 observations over time and space than the prediction with the BAU emission. The results show that the recession caused a 12ppbv decrease in surface O3 concentration over the eastern United States, a slight increase (0.51ppbv) over the Rocky Mountain region, and mixed changes in the Pacific West. The gain in air quality benefits during the recession, however, could be quickly offset by the much slower emission reduction rate during the post-recession period.

  5. Impact of the 2008 Global Recession on Air Quality over the United States: Implications for Surface Ozone Levels from Changes in NOx Emissions

    NASA Technical Reports Server (NTRS)

    Tong, Daniel; Pan, Li; Chen, Weiwei; Lamsal, Lok; Lee, Pius; Tang, Youhua; Kim, Hyuncheol; Kondragunta, Shobha; Stajner, Ivanka

    2016-01-01

    Satellite and ground observations detected large variability in nitrogen oxides (NOx) during the 2008 economic recession, but the impact of the recession on air quality has not been quantified. This study combines observed NOx trends and a regional chemical transport model to quantify the impact of the recession on surface ozone (O3) levels over the continental United States. The impact is quantified by simulating O3 concentrations under two emission scenarios: business-as-usual (BAU) and recession. In the BAU case, the emission projection from the Cross-State Air Pollution Rule is used to estimate the would-be NOx emission level in 2011. In the recession case, the actual NO2 trends observed from Air Quality System ground monitors and the Ozone Monitoring Instrument on the Aura satellite are used to obtain realistic changes in NOx emissions. The model prediction with the recession effect agrees better with ground O3 observations over time and space than the prediction with the BAU emission. The results show that the recession caused a 12ppbv decrease in surface O3 concentration over the eastern United States, a slight increase (0.51ppbv) over the Rocky Mountain region, and mixed changes in the Pacific West. The gain in air quality benefits during the recession, however, could be quickly offset by the much slower emission reduction rate during the post-recession period.

  6. Diagnosis of rare inherited glyoxalate metabolic disorders through in-situ analysis of renal stones

    NASA Astrophysics Data System (ADS)

    Jacob, D. E.; Grohe, B.; Hoppe, B.; Beck, B. B.; Tessadri, R.

    2012-04-01

    The primary hyperoxalurias type I - III constitute rare autosomal-recessive inherited disorders of the human glyoxylate metabolism. By mechanisms that are ill understood progressive nephrocalcinosis and recurrent urolithiasis (kidney stone formation) often starting in early childhood, along with their secondary complications results in loss of nephron mass which progresses to end-stage renal failure over time. In the most frequent form, end-stage renal failure (ESRF) is the rule and combined liver/kidney transplantation respectively pre-emptive liver transplantation are the only causative treatment today. Hence, this contributes significantly to healthcare costs and early diagnosis is extremely important for a positive outcome for the patient. We are developing a stone-based diagnostic method by in-detail multi-methods investigation of the crystalline moiety in concert with urine and stone proteomics. Stone analysis will allow faster analysis at low-impact for the patients in the early stages of the disease. First results from combined spectroscopic (Raman, FTIR)and geochemical micro-analyses (Electron Microprobe and Laser Ablation ICP-MS) are presented here that show significant differences between stones from hyperoxaluria patients and those formed by patients without this disorder (idiopathic stones). Major differences exist in chemistry as well as in morphology and phase composition of the stones. Ca/P ratios and Mg contents differentiate between oxalate-stones from hyperoxaluria patients and idiopathic stones. Results show that also within the different subtypes of primary hyperoxaluria significant differences can be found in stone composition. These imply differences in stone formation which could be exploited for new therapeutic pathways. Furthermore, the results provide important feedback for suspected but yet unconfirmed cases of primary hyperoxaluria when used in concert with the genetic methods routinely applied.

  7. A novel mutation in LRSAM1 causes axonal Charcot-Marie-Tooth disease with dominant inheritance

    PubMed Central

    2014-01-01

    Background Charcot-Marie-Tooth disease (CMT) refers to a heterogeneous group of genetic motor and sensory neuropathies. According to the primary site of damage, a distinction is made between demyelinating and axonal forms (CMT1 and 2, respectively, when inherited as an autosomal dominant trait). Leucine-rich repeat and sterile alpha motif-containing protein 1 (LRSAM1) is a ubiquitin-protein ligase with a role in sorting internalised cell-surface receptor proteins. So far, mutations in the LRSAM1 gene have been shown to cause axonal CMT in three different families and can confer either dominant or recessive transmission of the disease. Case presentation We have identified a novel mutation in LRSAM1 in a small family with dominant axonal CMT. Electrophysiological studies show evidence of a sensory axonal neuropathy and are interesting in so far as giant motor unit action potentials (MUAPs) are present on needle electromyography (EMG), while motor nerve conduction studies including compound motor action potential (CMAP) amplitudes are completely normal. The underlying mutation c.2046+1G >T results in the loss of a splice donor site and the inclusion of 63 additional base pairs of intronic DNA into the aberrantly spliced transcript. This disrupts the catalytically active RING (Really Interesting New Gene) domain of LRSAM1. Conclusions Our findings suggest that, beyond the typical length-dependent degeneration of motor axons, damage of cell bodies in the anterior horn might play a role in LRSAM1-associated neuropathies. Moreover, in conjunction with other data in the literature, our results support a model, by which disruption of the C-terminal RING domain confers dominant negative properties to LRSAM1. PMID:24894446

  8. The influence of the wahlund effect on the consanguinity hypothesis: consequences for recessive disease incidence in a socially structured pakistani population.

    PubMed

    Overall, Andrew D J

    2009-01-01

    Standard population genetic theory predicts that the relative risk of inheriting recessive disorders between consanguineous and non-consanguineous populations can be manyfold. However, it is rarely considered that consanguineous populations might be composites of socially defined endogamous and genetically differentiated subpopulations. A recent study of a British Pakistani population found evidence to suggest that extended families (biraderi) could contribute significantly to excessive homozygosity over that contributed by consanguinity. This study sets out to illustrate the potential of cryptic population substructure (the Wahlund effect) to contribute to recessive disease incidence in populations with complex social structure. Population parameter estimates were drawn from a recent study of the British Pakistani population along with allele frequency estimates of nine recessive inborn errors of metabolism. The relative contribution of consanguinity and biraderi endogamy to recessive disease incidence was predicted. Population substructure of the magnitude estimated from studies of biraderi endogamy are sufficient to significantly contribute to the incidence of recessive disorders within consanguineous populations. Because non-consanguineous couples have a higher risk of sharing the same recessive mutation in a substructured population relative to a non-substructured population, the health benefits of avoiding consanguinity in these situations is likely to be less pronounced than the standard consanguinity hypothesis predicts. Copyright 2008 S. Karger AG, Basel.

  9. Whole-exome sequencing identifies LRIT3 mutations as a cause of autosomal-recessive complete congenital stationary night blindness.

    PubMed

    Zeitz, Christina; Jacobson, Samuel G; Hamel, Christian P; Bujakowska, Kinga; Neuillé, Marion; Orhan, Elise; Zanlonghi, Xavier; Lancelot, Marie-Elise; Michiels, Christelle; Schwartz, Sharon B; Bocquet, Béatrice; Antonio, Aline; Audier, Claire; Letexier, Mélanie; Saraiva, Jean-Paul; Luu, Tien D; Sennlaub, Florian; Nguyen, Hoan; Poch, Olivier; Dollfus, Hélène; Lecompte, Odile; Kohl, Susanne; Sahel, José-Alain; Bhattacharya, Shomi S; Audo, Isabelle

    2013-01-10

    Congenital stationary night blindness (CSNB) is a clinically and genetically heterogeneous retinal disorder. Two forms can be distinguished clinically: complete CSNB (cCSNB) and incomplete CSNB. Individuals with cCSNB have visual impairment under low-light conditions and show a characteristic electroretinogram (ERG). The b-wave amplitude is severely reduced in the dark-adapted state of the ERG, representing abnormal function of ON bipolar cells. Furthermore, individuals with cCSNB can show other ocular features such as nystagmus, myopia, and strabismus and can have reduced visual acuity and abnormalities of the cone ERG waveform. The mode of inheritance of this form can be X-linked or autosomal recessive, and the dysfunction of four genes (NYX, GRM6, TRPM1, and GPR179) has been described so far. Whole-exome sequencing in one simplex cCSNB case lacking mutations in the known genes led to the identification of a missense mutation (c.983G>A [p.Cys328Tyr]) and a nonsense mutation (c.1318C>T [p.Arg440(∗)]) in LRIT3, encoding leucine-rich-repeat (LRR), immunoglobulin-like, and transmembrane-domain 3 (LRIT3). Subsequent Sanger sequencing of 89 individuals with CSNB identified another cCSNB case harboring a nonsense mutation (c.1151C>G [p.Ser384(∗)]) and a deletion predicted to lead to a premature stop codon (c.1538_1539del [p.Ser513Cysfs(∗)59]) in the same gene. Human LRIT3 antibody staining revealed in the outer plexiform layer of the human retina a punctate-labeling pattern resembling the dendritic tips of bipolar cells; similar patterns have been observed for other proteins implicated in cCSNB. The exact role of this LRR protein in cCSNB remains to be elucidated.

  10. Whole-Exome Sequencing Identifies LRIT3 Mutations as a Cause of Autosomal-Recessive Complete Congenital Stationary Night Blindness

    PubMed Central

    Zeitz, Christina; Jacobson, Samuel G.; Hamel, Christian P.; Bujakowska, Kinga; Neuillé, Marion; Orhan, Elise; Zanlonghi, Xavier; Lancelot, Marie-Elise; Michiels, Christelle; Schwartz, Sharon B.; Bocquet, Béatrice; Antonio, Aline; Audier, Claire; Letexier, Mélanie; Saraiva, Jean-Paul; Luu, Tien D.; Sennlaub, Florian; Nguyen, Hoan; Poch, Olivier; Dollfus, Hélène; Lecompte, Odile; Kohl, Susanne; Sahel, José-Alain; Bhattacharya, Shomi S.; Audo, Isabelle

    2013-01-01

    Congenital stationary night blindness (CSNB) is a clinically and genetically heterogeneous retinal disorder. Two forms can be distinguished clinically: complete CSNB (cCSNB) and incomplete CSNB. Individuals with cCSNB have visual impairment under low-light conditions and show a characteristic electroretinogram (ERG). The b-wave amplitude is severely reduced in the dark-adapted state of the ERG, representing abnormal function of ON bipolar cells. Furthermore, individuals with cCSNB can show other ocular features such as nystagmus, myopia, and strabismus and can have reduced visual acuity and abnormalities of the cone ERG waveform. The mode of inheritance of this form can be X-linked or autosomal recessive, and the dysfunction of four genes (NYX, GRM6, TRPM1, and GPR179) has been described so far. Whole-exome sequencing in one simplex cCSNB case lacking mutations in the known genes led to the identification of a missense mutation (c.983G>A [p.Cys328Tyr]) and a nonsense mutation (c.1318C>T [p.Arg440∗]) in LRIT3, encoding leucine-rich-repeat (LRR), immunoglobulin-like, and transmembrane-domain 3 (LRIT3). Subsequent Sanger sequencing of 89 individuals with CSNB identified another cCSNB case harboring a nonsense mutation (c.1151C>G [p.Ser384∗]) and a deletion predicted to lead to a premature stop codon (c.1538_1539del [p.Ser513Cysfs∗59]) in the same gene. Human LRIT3 antibody staining revealed in the outer plexiform layer of the human retina a punctate-labeling pattern resembling the dendritic tips of bipolar cells; similar patterns have been observed for other proteins implicated in cCSNB. The exact role of this LRR protein in cCSNB remains to be elucidated. PMID:23246293

  11. Legal Portion in Russian Inheritance Law

    ERIC Educational Resources Information Center

    Inshina, Roza; Murzalimova, Lyudmila

    2013-01-01

    In this paper the authors describe the right to inherit as one of the basic human rights guaranteed by the Constitution of the Russian Federation. The state has set rules according to which after a person's death, his or her property is inherited by other persons. The Russian civil legislation establishes the institution of legal portions that is…

  12. Inherited Bone Marrow Failure Syndromes (IBMFS)

    Cancer.gov

    The NCI IBMFS Cohort Study consists of affected individuals and their immediate families in North America who have an inherited bone marrow failure syndrome (IBMFS)-either one that has been specifically identified and defined, or bone marrow failure that appears to be inherited but has not yet been clearly identified as having a genetic basis.

  13. 25 CFR 213.13 - Inherited lands.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 1 2012-04-01 2011-04-01 true Inherited lands. 213.13 Section 213.13 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ENERGY AND MINERALS LEASING OF RESTRICTED LANDS OF MEMBERS OF FIVE CIVILIZED TRIBES, OKLAHOMA, FOR MINING How to Acquire Leases § 213.13 Inherited lands. Except to...

  14. 25 CFR 213.13 - Inherited lands.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 1 2013-04-01 2013-04-01 false Inherited lands. 213.13 Section 213.13 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ENERGY AND MINERALS LEASING OF RESTRICTED LANDS OF MEMBERS OF FIVE CIVILIZED TRIBES, OKLAHOMA, FOR MINING How to Acquire Leases § 213.13 Inherited lands. Except to...

  15. 25 CFR 213.13 - Inherited lands.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Inherited lands. 213.13 Section 213.13 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ENERGY AND MINERALS LEASING OF RESTRICTED LANDS OF MEMBERS OF FIVE CIVILIZED TRIBES, OKLAHOMA, FOR MINING How to Acquire Leases § 213.13 Inherited lands. Except to...

  16. 25 CFR 213.13 - Inherited lands.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 1 2011-04-01 2011-04-01 false Inherited lands. 213.13 Section 213.13 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ENERGY AND MINERALS LEASING OF RESTRICTED LANDS OF MEMBERS OF FIVE CIVILIZED TRIBES, OKLAHOMA, FOR MINING How to Acquire Leases § 213.13 Inherited lands. Except to...

  17. 25 CFR 213.13 - Inherited lands.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 1 2014-04-01 2014-04-01 false Inherited lands. 213.13 Section 213.13 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ENERGY AND MINERALS LEASING OF RESTRICTED LANDS OF MEMBERS OF FIVE CIVILIZED TRIBES, OKLAHOMA, FOR MINING How to Acquire Leases § 213.13 Inherited lands. Except to...

  18. Molecular analysis of ABCA4 and CRB1 genes in a Spanish family segregating both Stargardt disease and autosomal recessive retinitis pigmentosa

    PubMed Central

    Vallespin, Elena; Wilke, Robert; Garcia-Sandoval, Blanca; Cantalapiedra, Diego; Aguirre-Lamban, Jana; Avila-Fernandez, Almudena; Gimenez, Ascension; Trujillo-Tiebas, Maria-Jose; Ayuso, Carmen

    2008-01-01

    Purpose Stargardt disease (STGD), characterized by central visual impairment, is the most common juvenile macular dystrophy. All recessively inherited cases are thought to be due to mutations in the ABCA4 gene. Early-onset autosomal recessive retinitis pigmentosa (arRP) is a severe retinal degeneration that presents before the patient is ten years old. It has been associated with mutations in different genes, including CRB1. The aim of this study was to determine the genetic causes for two different retinal dystrophies, STGD and early-onset arRP, both segregating in one Spanish family. Methods Mutational analyses were performed using the ABCR400 and Leber congenital amaurosis (LCA) genotyping microarrays. Additional scanning for mutations was conducted by denaturing high performance liquid chromatography (dHPLC); results were confirmed by direct sequencing. Results A patient, who exhibited a STGD phenotype, was found to be homozygous for the p.Asn1805Asp (c.5413A>G) mutation in ABCA4. However, his affected sister, who had the arRP phenotype, was found to be heterozygous for this allele; no other sequence change could be found in ABCA4. Analysis using the LCA chip revealed the p.Cys948Tyr mutation in CRB1 in heterozygous state. A second mutation (p.Trp822ter) was found in the CRB1 gene in the affected female by denaturing high performance liquid chromatography (dHPLC) and direct sequencing. Conclusions Two distinct retinal dystrophies with mutations affecting two different genes cosegregated in this family. The presence of two different phenotypes associated with mutations in two distinct genes in one single family must be considered especially when dealing with retinal dystrophies which bear high carrier frequencies in general population. PMID:18334942

  19. The Muscle Chloride Channel ClC-1 Has a Double-Barreled Appearance that Is Differentially Affected in Dominant and Recessive Myotonia

    PubMed Central

    Saviane, Chiara; Conti, Franco; Pusch, Michael

    1999-01-01

    Single-channel recordings of the currents mediated by the muscle Cl− channel, ClC-1, expressed in Xenopus oocytes, provide the first direct evidence that this channel has two equidistant open conductance levels like the Torpedo ClC-0 prototype. As for the case of ClC-0, the probabilities and dwell times of the closed and conducting states are consistent with the presence of two independently gated pathways with ≈ 1.2 pS conductance enabled in parallel via a common gate. However, the voltage dependence of the common gate is different and the kinetics are much faster than for ClC-0. Estimates of single-channel parameters from the analysis of macroscopic current fluctuations agree with those from single-channel recordings. Fluctuation analysis was used to characterize changes in the apparent double-gate behavior of the ClC-1 mutations I290M and I556N causing, respectively, a dominant and a recessive form of myotonia. We find that both mutations reduce about equally the open probability of single protopores and that mutation I290M yields a stronger reduction of the common gate open probability than mutation I556N. Our results suggest that the mammalian ClC-homologues have the same structure and mechanism proposed for the Torpedo channel ClC-0. Differential effects on the two gates that appear to modulate the activation of ClC-1 channels may be important determinants for the different patterns of inheritance of dominant and recessive ClC-1 mutations. PMID:10051520

  20. Missense Mutations in CRYAB Are Liable for Recessive Congenital Cataracts

    PubMed Central

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

    2015-01-01

    Purpose This study was initiated to identify causal mutations responsible for autosomal recessive congenital cataracts in consanguineous familial cases. Methods Affected individuals underwent a detailed ophthalmological and clinical examination, and slit-lamp photographs were ascertained for affected individuals who have not yet been operated for the removal of the cataractous lens. Blood samples were obtained, and genomic DNA was extracted from white blood cells. A genome-wide scan was completed with short tandem repeat (STR) markers, and the logarithm of odds (LOD) scores were calculated. Protein coding exons of CRYAB were sequenced, bi-directionally. Evolutionary conservation was investigated by aligning CRYAB orthologues, and the expression of Cryab in embryonic and postnatal mice lens was investigated with TaqMan probe. Results The clinical and ophthalmological examinations suggested that all affected individuals had nuclear cataracts. Genome-wide linkage analysis suggested a potential region on chromosome 11q23 harboring CRYAB. DNA sequencing identified a missense variation: c.34C>T (p.R12C) in CRYAB that segregated with the disease phenotype in the family. Subsequent interrogation of our entire cohort of familial cases identified a second familial case localized to chromosome 11q23 harboring a c.31C>T (p.R11C) mutation. In silico analyses suggested that the mutations identified in familial cases, p.R11C and p.R12C will not be tolerated by the three-dimensional structure of CRYAB. Real-time PCR analysis identified the expression of Cryab in mouse lens as early as embryonic day 15 (E15) that increased significantly until postnatal day 6 (P6) with steady level of expression thereafter. Conclusion Here, we report two novel missense mutations, p.R11C and p.R12C, in CRYAB associated with autosomal recessive congenital nuclear cataracts. PMID:26402864