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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. 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.

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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 ...

  20. Autosomal Recessive Inheritance

    MedlinePlus

    ... Courier services use: Rockville, MD 20852) 301-451-2020 Research at NEI Office of the Scientific Director ... Eye Disease Education Program Glaucoma Education Program Low Vision Education Program Hispanic/Latino Program Vision and Aging ...

  1. 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

    2017-01-17

    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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. 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…

  4. 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.

  5. 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

  6. 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.

  7. Autosomal recessive hypercholesterolemia.

    PubMed

    Soutar, Anne K; Naoumova, Rossitza P

    2004-08-01

    Autosomal recessive hypercholesterolemia (ARH) presents with a clinical phenotype similar to that of classical homozygous familial hypercholesterolemia (FH) caused by defects in the low-density lipoprotein (LDL) receptor gene but is more variable, generally less severe, and more responsive to lipid-lowering therapy than homozygous FH; furthermore, FH is inherited with a dominant pattern. The approximately 50 known affected ARH individuals are mostly of Sardinian or Middle Eastern origin, but rare cases of ARH have occurred worldwide. The physiological defect in ARH is a failure of some, but not all, cell types to mediate LDL receptor-dependent internalization of LDL and is caused by mutations in the gene for a putative adaptor protein called ARH. In affected cells, the LDL receptor gene is normal but LDL receptor protein accumulates at the cell surface; this also occurs in livers of recombinant mice lacking ARH, providing an explanation for the failure of clearance of LDL from plasma in ARH patients. The structural features of the ARH protein and its capacity to interact with the internalization sequence of the LDL receptor, plasma membrane phospholipids, and the clathrin endocytic machinery suggest that it plays a key role in the LDL receptor pathway.

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. [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.

  15. 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

  16. 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

  17. 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

  18. 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…

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. 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

  8. [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.

  9. 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…

  10. 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.

  11. 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

  12. 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

  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. [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.

  15. 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.

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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…

  6. 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)…

  7. 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…

  8. 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…

  9. 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

  10. 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

  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. 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.

  13. 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

  14. 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

  15. [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.

  16. 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.

  17. [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.

  18. 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.

  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. 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.

  1. 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.

  2. 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

  3. 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…

  4. [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.

  5. 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.

  6. 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)

  7. 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.

  8. 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.

  9. 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)

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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…

  17. 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…

  18. 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. 

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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.

  7. 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

  8. 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…

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. 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

  14. 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.

  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. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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)

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. 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

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. 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…

  4. 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)…

  5. 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.

  6. 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.

  7. 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?

  8. 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

  9. 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.

  10. [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.

  11. 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

  12. 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…

  13. 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.

  14. 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

  15. [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%.

  16. 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

  17. 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.

  18. 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

  19. 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.

  20. [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.

  1. 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.

  2. 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.

  3. 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.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  5. 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.

  6. Molecular mechanisms of autosomal recessive hypercholesterolemia.

    PubMed

    Wilund, Kenneth R; Yi, Ming; Campagna, Filomena; Arca, Marcello; Zuliani, Giovanni; Fellin, Renato; Ho, Yiu-Kee; Garcia, J Victor; Hobbs, Helen H; Cohen, Jonathan C

    2002-11-15

    Mutations in the phosphotyrosine-binding domain protein ARH cause autosomal recessive hypercholesterolemia (ARH), an inherited form of hypercholesterolemia due to a tissue-specific defect in the removal of low density lipoproteins (LDL) from the circulation. LDL uptake by the LDL receptor (LDLR) is markedly reduced in the liver but is normal or only moderately impaired in cultured fibroblasts of ARH patients. To define the molecular mechanism underlying ARH we examined ARH mRNA and protein in fibroblasts and lymphocytes from six probands with different ARH mutations. None of the probands had detectable full-length ARH protein in fibroblasts or lymphoblasts. Five probands were homozygous for mutations that introduced premature termination codons. No relationship was apparent between the site of the mutation in ARH and the amount of mRNA. The only mutation identified in the remaining proband was a SINE VNTR Alu (SVA) retroposon insertion in intron 1, which was associated with no detectable ARH mRNA. (125)I-LDL degradation was normal in ARH fibroblasts, as previously reported. In contrast, LDLR function was markedly reduced in ARH lymphoblasts, despite a 2-fold increase in LDL cell surface binding in these cells. These data indicate that all ARH mutations characterized to date preclude the synthesis of full-length ARH and that ARH is required for normal LDLR function in lymphocytes and hepatocytes, but not in fibroblasts. Residual LDLR function in cells that do not require ARH may explain why ARH patients have lower plasma LDL levels than do patients with homozygous familial hypercholesterolemia who have no functional LDLRs.

  7. 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.

  8. 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.

  9. 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

  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. 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

  12. 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

  13. 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

  14. 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

  15. 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.

  16. 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

  17. “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

  18. 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…

  19. 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…

  20. 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…

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. 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)

  12. 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

  13. Genetics Home Reference: autosomal recessive primary microcephaly

    MedlinePlus

    ... This Page Cox J, Jackson AP, Bond J, Woods CG. What primary microcephaly can tell us about ... Mannon J, Rashid Y, Crow Y, Bond J, Woods CG. Autosomal recessive primary microcephaly: an analysis of ...

  14. 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, ...

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. 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

  8. [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.

  9. 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

  10. 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.

  11. [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.

  12. 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.

  13. 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

  14. 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

  15. 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".

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. Primary Immune Deficiency Disease Genetics & Inheritance

    MedlinePlus

    ... twitter share with linkedin Primary Immune Deficiency Disease Genetics & Inheritance Primary Immune Deficiency Diseases (PIDDs) Primary Immune Deficiency Diseases (PIDDs) Types of PIDDs Genetics & Inheritance Talking to Your Doctor Featured Research Credit: ...

  8. Rare genetic causes of autosomal dominant or recessive hypercholesterolaemia.

    PubMed

    Soutar, Anne K

    2010-02-01

    Familial hypercholesterolaemia (FH) is a human inherited disorder of metabolism characterised by increased serum low-density lipoprotein (LDL) cholesterol. It is caused by defects in the LDL-receptor pathway that impair normal uptake and clearance of LDL by the liver. The commonest cause of FH is mutations in LDLR, the gene for the LDL receptor, but defects also occur in APOB that encodes its major protein ligand. More recently, defects in two other genes, LDLRAP1 and PCSK9, have been found in patients with FH and investigation of these has shed new light on the functioning and complexity of the LDL receptor pathway. Cells from patients with autosomal recessive hypercholesterolaemia (ARH) fail to internalise the LDL receptor because they carry two defective alleles of LDLRAP1, a gene that encodes a specific clathrin adaptor protein. PCSK9 encodes proprotein convertase subtilisin kexin type 9, a secreted protein that binds to the LDL receptor and promotes its degradation. Gain-of function mutations in PCSK9 are autosomal dominant and cause hypercholesterolaemia because they increase the affinity of PCSK9 protein for the LDL receptor, whereas loss-of-function mutations reduce serum cholesterol because LDL-receptor protein is exposed to reduced PCSK9-mediated degradation. Thus, PCSK9 has become a new target for cholesterol-lowering drug therapy.

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. [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.

  17. [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.

  18. 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…

  19. 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…

  20. 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…

  1. 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.

  2. 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.

  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. 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

  5. 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.

  6. 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.

  7. The autosomal recessive hypercholesterolemia (ARH) protein interfaces directly with the clathrin-coat machinery.

    PubMed

    Mishra, Sanjay K; Watkins, Simon C; Traub, Linton M

    2002-12-10

    The low density lipoprotein (LDL) receptor plays a pivotal role in cholesterol metabolism. Inherited mutations that disturb the activity of the receptor lead to elevations in plasma cholesterol levels and early-onset coronary atherosclerosis. Defects in either the LDL receptor or apolipoprotein B, the proteinaceous component of LDL particles that binds the LDL receptor, elevate circulating LDL-cholesterol levels in an autosomal-dominant fashion, with heterozygotes displaying values between homozygous and normal individuals. Rarely, similar clinical phenotypes occur with a recessive pattern of inheritance, and several genetic lesions in the autosomal recessive hypercholesterolemia (ARH) gene on chromosome 1 have been mapped in this class of patients. ARH has an N-terminal phosphotyrosine-binding (PTB) domain evolutionarily related to that found in Disabled-2 and numb, two endocytic proteins. PTB domains bind to the consensus sequence FXNPXY, corresponding to the internalization motif of the LDL receptor. We show here that in addition to the FXNPXY sequence, ARH binds directly to soluble clathrin trimers and to clathrin adaptors by a mode involving the independently folded appendage domain of the beta subunit. At steady state, ARH colocalizes with endocytic proteins in HeLa cells, and the LDL receptor fluxes through peripheral ARH-positive sites before delivery to early endosomes. Because ARH also binds directly to phosphoinositides, which regulate clathrin bud assembly at the cell surface, our data suggest that in ARH patients, defective sorting adaptor function in hepatocytes leads to faulty LDL receptor traffic and hypercholesterolemia.

  8. 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

  9. 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

  10. [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.

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  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. 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.

  2. 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.

  3. 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.

  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. 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.

  7. 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

  8. 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.

  9. 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

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. 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

  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. 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

  19. Tag, catch, and other unnatural acts at recess (Circa 2014).

    PubMed

    Sydnor, Synthia

    2014-03-01

    This commentary details a news event in which Carrie Weber Middle School in Port Washington, NY, supposedly banned students from using balls, playing tag, and doing cartwheels during recess. Public reaction in the form of news items, tweets, blogs, and commentary is sampled, and news releases from the Weber Middle School that were barely covered by the media and explain their decision to ban hardballs from 20-min recess are brought to light. The commentary then goes on to argue that such trending news events can be interpreted in terms of complex cultural histories, including in the case of Weber Middle School, much intellectual thought pioneered by human movement scholarship. Ideas about social nostalgia and memory, play, hegemony, invention of tradition, and cultural context are overviewed in light of their use in human movement studies and in interpreting the Weber Middle School issue. It is argued that current issues and initiatives surrounding obesity and sport for peace and development are, like the trending Weber Middle School news, sometimes not mapped or critiqued (terms coined by Markula-Denison and Silk in 2011) in the profound ways that cultural studies urge. The commentary ends in a call to scholars and practitioners of human movement studies for self-reflexivity and purposeful awareness of changing social definitions of the "unnatural."

  20. 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.

  1. 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

  2. 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

  3. Autosomal recessive cerebellar ataxia of adult onset due to STUB1 mutations.

    PubMed

    Depondt, Chantal; Donatello, Simona; Simonis, Nicolas; Rai, Myriam; van Heurck, Roxane; Abramowicz, Marc; D'Hooghe, Marc; Pandolfo, Massimo

    2014-05-13

    Autosomal recessive ataxias affect about 1 person in 20,000. Friedreich ataxia accounts for one-third of the cases in Caucasians; the others are due to a growing list of very rare molecular defects, including mild forms of metabolic diseases. In nearly 50%, the genetic cause remains undetermined.

  4. Organizational Adaptation of Liberal Arts Colleges during the Great Recession of 2007

    ERIC Educational Resources Information Center

    Hilbun, Ashlie Junot; Mamiseishvili, Ketevan

    2016-01-01

    The study we report here explored how private liberal arts colleges adapted to the Great Recession of 2007. We examined institutional changes at three private liberal arts colleges and their effects on the institutions' operations. For this multiple-case study we analyzed data from three colleges in the southeastern region of the United States;…

  5. Management of gingival recession with acellular dermal matrix graft: A clinical study

    PubMed Central

    Balaji, V. R.; Ramakrishnan, T.; Manikandan, D.; Lambodharan, R.; Karthikeyan, B.; Niazi, Thanvir Mohammed; Ulaganathan, G.

    2016-01-01

    Aims and Objectives: Obtaining root coverage has become an important part of periodontal therapy. The aims of this studyare to evaluate the clinical efficacy of acellular dermal matrix graft in the coverage of denuded roots and also to examine the change in the width of keratinized gingiva. Materials and Methods: A total of 20 sites with more than or equal to 2 mm of recession depth were taken into the study, for treatment with acellular dermal matrix graft. The clinical parameters such as recession depth, recession width, width of keratinized gingiva, probing pocket depth (PD), and clinical attachment level (CAL) were measured at the baseline, 8th week, and at the end of the study (16th week). The defects were treated with a coronally positioned pedicle graft combined with acellular dermal matrix graft. Results: Out of 20 sites treated with acellular dermal matrix graft, seven sites showed complete root coverage (100%), and the mean root coverage obtained was 73.39%. There was a statistically significant reduction in recession depth, recession width, and probing PD. There was also a statistically significant increase in width of keratinized gingiva and also gain in CAL. The postoperative results were both clinically and statistically significant (P < 0.0001). Conclusion: The results of this study were esthetically acceptable to the patients and clinically acceptable in all cases. From this study, it may be concluded that acellular dermal matrix graft is an excellent substitute for autogenous graft in coverage of denuded roots. PMID:27829749

  6. Analytical approximations of discharge recessions for steeply sloping aquifers in alpine catchments

    NASA Astrophysics Data System (ADS)

    Pauritsch, Marcus; Birk, Steffen; Wagner, Thomas; Hergarten, Stefan; Winkler, Gerfried

    2015-11-01

    The validity and applicability of various methods to infer hydraulic properties of sloping aquifers in alpine settings using the power law relationship between the discharge recession and its first time derivative is explored. For this purpose, a synthetic spring catchment implemented in the numerical groundwater flow model MODFLOW as well as the example of a relict rock glacier in an alpine setting is examined. The various approaches are found to differ particularly in the late time domain, whereas most of them agree fairly well in the early time domain and at the transition point between the two time domains. As the early recession may be affected by uncertainties from inappropriate initial conditions, it is proposed to use the transition point for estimating aquifer thickness and transmissivity. Using only prolonged winter recessions in the analysis of the field data from the relict rock glacier yields estimates of aquifer thickness and hydraulic conductivity consistent with results from a geophysical survey and tracer tests, respectively. In the other seasons, the recession is frequently interrupted by minor recharge events, and using the lower envelope of the entire data is found to yield estimates that are too high in the given case. It is thus recommended to focus on the winter recession in the analysis of hydrograph data from alpine settings.

  7. 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.

  8. Event-scale power law recession analysis: quantifying methodological uncertainty

    NASA Astrophysics Data System (ADS)

    Dralle, David N.; Karst, Nathaniel J.; Charalampous, Kyriakos; Veenstra, Andrew; Thompson, Sally E.

    2017-01-01

    The study of single streamflow recession events is receiving increasing attention following the presentation of novel theoretical explanations for the emergence of power law forms of the recession relationship, and drivers of its variability. Individually characterizing streamflow recessions often involves describing the similarities and differences between model parameters fitted to each recession time series. Significant methodological sensitivity has been identified in the fitting and parameterization of models that describe populations of many recessions, but the dependence of estimated model parameters on methodological choices has not been evaluated for event-by-event forms of analysis. Here, we use daily streamflow data from 16 catchments in northern California and southern Oregon to investigate how combinations of commonly used streamflow recession definitions and fitting techniques impact parameter estimates of a widely used power law recession model. Results are relevant to watersheds that are relatively steep, forested, and rain-dominated. The highly seasonal mediterranean climate of northern California and southern Oregon ensures study catchments explore a wide range of recession behaviors and wetness states, ideal for a sensitivity analysis. In such catchments, we show the following: (i) methodological decisions, including ones that have received little attention in the literature, can impact parameter value estimates and model goodness of fit; (ii) the central tendencies of event-scale recession parameter probability distributions are largely robust to methodological choices, in the sense that differing methods rank catchments similarly according to the medians of these distributions; (iii) recession parameter distributions are method-dependent, but roughly catchment-independent, such that changing the choices made about a particular method affects a given parameter in similar ways across most catchments; and (iv) the observed correlative relationship

  9. What mainly controls recession flows in river basins?

    NASA Astrophysics Data System (ADS)

    Biswal, Basudev; Nagesh Kumar, D.

    2014-03-01

    The ubiquity of the power law relationship between dQ/dt and Q for recession periods (-dQ/dt=kQα,Q being discharge at the basin outlet at time t) clearly hints at the existence of a dominant recession flow process that is common to all real basins. It is commonly assumed that a basin, during recession events, functions as a single phreatic aquifer resting on a impermeable horizontal bed or the Dupuit-Boussinesq (DB) aquifer, and with time different aquifer geometric conditions arise that give different values of α and k. The recently proposed alternative model, geomorphological recession flow model, however, suggests that recession flows are controlled primarily by the dynamics of the active drainage network (ADN). In this study we use data for several basins and compare the above two contrasting recession flow models in order to understand which of the above two factors dominates during recession periods in steep basins. Particularly, we do the comparison by selecting three key recession flow properties: (1) power law exponent α, (2) dynamic dQ/dt-Q relationship (characterized by k) and (3) recession timescale (time period for which a recession event lasts). Our observations suggest that neither drainage from phreatic aquifers nor evapotranspiration significantly controls recession flows. Results show that the value of α and recession timescale are not modeled well by DB aquifer model. However, the above mentioned three recession curve properties can be captured satisfactorily by considering the dynamics of the ADN as described by geomorphological recession flow model, possibly indicating that the ADN represents not just phreatic aquifers but the organization of various sub-surface storage systems within the basin.

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. Nonsyndromic autosomal recessive deafness is linked to the DFNB1 locus in a large inbred Bedouin family from Israel

    SciTech Connect

    Scott, D.A.; Sheffield, V.C.; Stone, E.M.

    1995-10-01

    Nonsyndromic deafness accounts for {approximately}70% of all genetically determined deafness. Several types of nonsyndromic deafness, with a variety of inheritance patterns, have been genetically linked, including dominant, recessive and X-linked forms. Two of these forms - DFNA3, a dominant form causing moderate to severe hearing loss, predominantly in the high frequencies, and DFNB1, a recessive form causing profound, prelingual, neurosensory deafness affecting all frequencies - have been linked to the same pericentromeric region of chromosome 13. This finding is equally compatible with (1) the existence two closely linked deafness genes, (2) different mutations within a single deafness gene, and (3) a single mutation in a single gene that behaves differently in different genetic backgrounds. 12 refs., 2 figs., 1 tab.

  15. 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.

  16. 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

  17. A Case of Carbonic Anhydrase Type 2 Deficiency Syndrome with Autistic Disorder

    PubMed Central

    KILIÇ, Birim Günay; UĞUR, Çağatay; SADAY DUMAN, Nagihan; AKÇAKIN, Melda

    2014-01-01

    Carbonic Anhydrase Type II Deficiency Syndrome (CADS) is a disease with an autosomal recessive inheritance that mainly includes characteristics of osteopetrosis, renal tubular acidosis and cerebral calcification. Pathological fractures, poor vision due to cranial nerve pressure, wide forehead, disproportionate mouth and jaw, physical and mental developmental delay are other features. In this paper, we present the case of a patient who was referred to our department with a diagnosis of CADS and diagnosed with autistic disorder after a psychiatric evaluation. We performed a detailed literature search, however, we did not find any report of co-existence of CADS (osteopetrosis intermediate type) and autistic disorder.

  18. ALS5/SPG11/KIAA1840 mutations cause autosomal recessive axonal Charcot-Marie-Tooth disease.

    PubMed

    Montecchiani, Celeste; Pedace, Lucia; Lo Giudice, Temistocle; Casella, Antonella; Mearini, Marzia; Gaudiello, Fabrizio; Pedroso, José L; Terracciano, Chiara; Caltagirone, Carlo; Massa, Roberto; St George-Hyslop, Peter H; Barsottini, Orlando G P; Kawarai, Toshitaka; Orlacchio, Antonio

    2016-01-01

    Charcot-Marie-Tooth disease is a group of hereditary peripheral neuropathies that share clinical characteristics of progressive distal muscle weakness and atrophy, foot deformities, distal sensory loss, as well as diminished tendon reflexes. Hundreds of causative DNA changes have been found, but much of the genetic basis of the disease is still unexplained. Mutations in the ALS5/SPG11/KIAA1840 gene are a frequent cause of autosomal recessive hereditary spastic paraplegia with thin corpus callosum and peripheral axonal neuropathy, and account for ∼ 40% of autosomal recessive juvenile amyotrophic lateral sclerosis. The overlap of axonal Charcot-Marie-Tooth disease with both diseases, as well as the common autosomal recessive inheritance pattern of thin corpus callosum and axonal Charcot-Marie-Tooth disease in three related patients, prompted us to analyse the ALS5/SPG11/KIAA1840 gene in affected individuals with autosomal recessive axonal Charcot-Marie-Tooth disease. We investigated 28 unrelated families with autosomal recessive axonal Charcot-Marie-Tooth disease defined by clinical, electrophysiological, as well as pathological evaluation. Besides, we screened for all the known genes related to axonal autosomal recessive Charcot-Marie-Tooth disease (CMT2A2/HMSN2A2/MFN2, CMT2B1/LMNA, CMT2B2/MED25, CMT2B5/NEFL, ARCMT2F/dHMN2B/HSPB1, CMT2K/GDAP1, CMT2P/LRSAM1, CMT2R/TRIM2, CMT2S/IGHMBP2, CMT2T/HSJ1, CMTRID/COX6A1, ARAN-NM/HINT and GAN/GAN), for the genes related to autosomal recessive hereditary spastic paraplegia with thin corpus callosum and axonal peripheral neuropathy (SPG7/PGN, SPG15/ZFYVE26, SPG21/ACP33, SPG35/FA2H, SPG46/GBA2, SPG55/C12orf65 and SPG56/CYP2U1), as well as for the causative gene of peripheral neuropathy with or without agenesis of the corpus callosum (SLC12A6). Mitochondrial disorders related to Charcot-Marie-Tooth disease type 2 were also excluded by sequencing POLG and TYMP genes. An additional locus for autosomal recessive Charcot

  19. CFLs in Recessed Downlights: Technical Challenges

    SciTech Connect

    Ledbetter, Marc R.; McCullough, Jeffrey J.; Dillon, Heather E.; Sandahl, Linda J.; Gordon, Kelly L.

    2005-05-09

    Recessed downlights are the most popular residential lighting fixture in the United States representing about 12 percent of installed residential lighting fixtures and 15 percent of total lighting energy use nationwide. We estimate 400 million recessed downlights are currently installed in American homes, almost all using incandescent light sources. In the year 2000, only 0.44 percent of recessed cans sold were hard-wired for using pin-based CFLs. Recessed downlights consume energy in three ways. First, their incandescent light sources use energy directly, drawing 65 to 150 watts. Second, they consume energy indirectly by adding heat from their light sources to air-conditioning loads. Third, since most are not airtight, they also consume energy indirectly by allowing conditioned air to escape into unconditioned areas above the downlights, such as attics. PNNL calculated potential energy savings and found that if a 65W incandescent non-airtight downlight is replaced with a 26W CFL ICAT downlight operated at 3 hrs per day savings will be 126 kWh/yr. Early reflector CFLs have had high return rates primarily because of failure due to thermal related stress. A PNNL laboratory test of ten commercially available R-CFLs selected from retail store shelves showed almost all operated above their manufacturer rated maximum operating temperatures when they were installed and tested in ICAT downlights in a simulated insulated ceiling apparatus. DOE asked PNNL to investigate the development and introduction of both pin-based and screw-based CFLs for use in ICAT fixtures. PNNL invited manufacturers to submit lamps to a procurement program. PNNL conducted short- and long-term thermal testing of the lamps to measure performance parameters affected by elevated temperatures. 8 out of 10 R-CFLs (secrew-based lamps) failed the long-tem testing. Five out of nine CFL-ICAT (pin-based CFL) fixtures passed the long-term test, surviving a full year of operation in a simulated insulated

  20. Familial mesial temporal lobe epilepsy: a benign epilepsy syndrome showing complex inheritance.

    PubMed

    Crompton, Douglas E; Scheffer, Ingrid E; Taylor, Isabella; Cook, Mark J; McKelvie, Penelope A; Vears, Danya F; Lawrence, Kate M; McMahon, Jacinta M; Grinton, Bronwyn E; McIntosh, Anne M; Berkovic, Samuel F

    2010-11-01

    Temporal lobe epilepsy is the commonest partial epilepsy of adulthood. Although generally perceived as an acquired disorder, several forms of familial temporal lobe epilepsy, with mesial or lateral seizure semiology, have been described. Descriptions of familial mesial temporal lobe epilepsy have varied widely from a benign epilepsy syndrome with prominent déjà vu and without antecedent febrile seizures or magnetic resonance imaging abnormalities, to heterogeneous, but generally more refractory epilepsies, often with a history of febrile seizures and with frequent hippocampal atrophy and high T₂ signal on magnetic resonance imaging. Compelling evidence of a genetic aetiology (rather than chance aggregation) in familial mesial temporal lobe epilepsy has come from twin studies. Dominant inheritance has been reported in two large families, though the usual mode of inheritance is not known. Here, we describe clinical and neurophysiological features of 20 new mesial temporal lobe epilepsy families including 51 affected individuals. The epilepsies in these families were generally benign, and febrile seizure history was infrequent (9.8%). No evidence of hippocampal sclerosis or dysplasia was present on brain imaging. A single individual underwent anterior temporal lobectomy, with subsequent seizure freedom and histopathological evidence of hippocampal sclerosis was not found. Inheritance patterns in probands' relatives were analysed in these families, together with 19 other temporal lobe epilepsy families previously reported by us. Observed frequencies of epilepsies in relatives were lower than predicted by dominant Mendelian models, while only a minority (8/39) of families could be compatible with recessive inheritance. These findings strongly suggest that complex inheritance, similar to that widely accepted in the idiopathic generalized epilepsies, is the usual mode of inheritance in familial mesial temporal lobe epilepsy. This disorder, which appears to be

  1. [Inheritance and expression of dominant genes with variable penetration: the evolutionary aspect].

    PubMed

    Ruvinskiĭ, A O

    1987-06-01

    According to up-to-date literature, one of the approaches to elucidating the essence of evolutionary events consists in admitting the importance of events which change genome activity. A crucial way of reorganization of gene activity is the inhetrited activation or inactivation of the genes. "Dormant" gene hypothesis and related data are reviewed in this connection. Most attention is concentrated on the study of inheritance and penetrance of fused gene in mice. By means of individual genetic analysis, it became possible to make a clear-cut distinction between the phenomenon of the lowered gene penetrance and its inherited inactivation. It was shown that low penetrance is a more frequent event which seems to mask the inherited inactivation of the gene. A general scheme of the phenomena studied is proposed. The classical conceptions claiming the existence of a reserve of hereditary variability concern mainly the recessive and codominant mutations. However, the role of dominant and semidominant mutations in the course of functional reconstruction of species may be important. During animal domestication, for example, everyone can see a lot of dominantly inherited characters appearing de novo. D.K. Belyaev's conception about "dormant" gene reserve is of great importance in this connection. Opening of the reserve at a particular evolutionary stage may drastically increase the genetic variability and lead to appearance of evolutionary novelty.

  2. Unravelling the genetic basis of simplex Retinitis Pigmentosa cases

    PubMed Central

    Bravo-Gil, Nereida; González-del Pozo, María; Martín-Sánchez, Marta; Méndez-Vidal, Cristina; Rodríguez-de la Rúa, Enrique; Borrego, Salud; Antiñolo, Guillermo

    2017-01-01

    Retinitis Pigmentosa (RP) is the most common form of inherited retinal dystrophy (IRD) characterized ultimately by photoreceptors degeneration. Exhibiting great clinical and genetic heterogeneity, RP can be inherited as an autosomal dominant (ad), autosomal recessive (ar) and X-linked (xl) disorder. Although the relative prevalence of each form varies somewhat between populations, a major proportion (41% in Spain) of patients represent simplex cases (sRP) in which the mode of inheritance is unknown. Molecular genetic diagnostic is crucial, but also challenging, for sRP patients because any of the 81 RP genes identified to date may be causative. Herein, we report the use of a customized targeted gene panel consisting of 68 IRD genes for the molecular characterization of 106 sRP cases. The diagnostic rate was 62.26% (66 of 106) with a proportion of clinical refinements of 30.3%, demonstrating the high efficiency of this genomic approach even for clinically ambiguous cases. The high number of patients diagnosed here has allowed us to study in detail the genetic basis of the sRP. The solved sRP cohort is composed of 62.1% of arRP cases, 24.2% of adRP and 13.6% of xlRP, which implies consequences for counselling of patients and families. PMID:28157192

  3. Unravelling the genetic basis of simplex Retinitis Pigmentosa cases.

    PubMed

    Bravo-Gil, Nereida; González-Del Pozo, María; Martín-Sánchez, Marta; Méndez-Vidal, Cristina; Rodríguez-de la Rúa, Enrique; Borrego, Salud; Antiñolo, Guillermo

    2017-02-03

    Retinitis Pigmentosa (RP) is the most common form of inherited retinal dystrophy (IRD) characterized ultimately by photoreceptors degeneration. Exhibiting great clinical and genetic heterogeneity, RP can be inherited as an autosomal dominant (ad), autosomal recessive (ar) and X-linked (xl) disorder. Although the relative prevalence of each form varies somewhat between populations, a major proportion (41% in Spain) of patients represent simplex cases (sRP) in which the mode of inheritance is unknown. Molecular genetic diagnostic is crucial, but also challenging, for sRP patients because any of the 81 RP genes identified to date may be causative. Herein, we report the use of a customized targeted gene panel consisting of 68 IRD genes for the molecular characterization of 106 sRP cases. The diagnostic rate was 62.26% (66 of 106) with a proportion of clinical refinements of 30.3%, demonstrating the high efficiency of this genomic approach even for clinically ambiguous cases. The high number of patients diagnosed here has allowed us to study in detail the genetic basis of the sRP. The solved sRP cohort is composed of 62.1% of arRP cases, 24.2% of adRP and 13.6% of xlRP, which implies consequences for counselling of patients and families.

  4. 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…

  5. 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.

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. Selection for male-enforced uniparental cytoplasmic inheritance.

    PubMed

    Sreedharan, Vandana; Shpak, Max

    2010-12-01

    In most sexually reproducing species, including humans, mitochondria and other cytoplasmic elements are uniparentally (usually maternally) inherited. This phenomenon is of broad interest as a mechanism for countering the proliferation of selfish mitochondria. Uniparental inheritance can be enforced either by the female gametes excluding male cytoplasm or male gametes excluding their own from the zygote. Previous studies have shown that male-enforced uniparental inheritance is unlikely to evolve as a primary mechanism, because unlike female enforcement, the positive linkage disequilibrium between the modifier for eliminating the gamete's own mitochondria and a wild-type mitochondrial complement is broken from one generation to the next. However, it has been proposed that with a sufficiently high mutation rate and strong selection, elimination of the gamete's own mitochondria could be favored by selection. In this article, a series of numerical simulations confirm that this is indeed the case, although the conditions where male enforcement is favored are quite restrictive. Specifically, in addition to a high mutation rate to selfish mitochondria and strong selection against them, the cost of uniparental inheritance must be negligible.

  12. Tectonic Inheritance at Transform Faults in Successive Wilson Cycles (Invited)

    NASA Astrophysics Data System (ADS)

    Thomas, W. A.

    2010-12-01

    Preservation of the record of two complete Wilson cycles along the eastern (Iapetan/Atlantic) margin of Laurentia/North America provides an unusual opportunity to study tectonic inheritance at continental margins in successive Wilson cycles. At the largest scale of tectonic inheritance, during continental rifting, transform faults offset rift segments, framing promontories and embayments of the continental margin; a subsequent orogenic belt adapts to the trace of the continental margin, curving around recesses and salients during supercontinent assembly. From observations of the Iapetan and Atlantic Wilson cycles, inheritance is expressed during continental rifting and ocean opening most strongly along transform faults/margins, and during closing and supercontinent assembly primarily in adaptation to the trace of the pre-orogenic margin and in foreland subsidence. The Alabama-Oklahoma transform and Southern Oklahoma transform-parallel intracratonic fault system of the Iapetan margin are parallel with a Mesoproterozoic dike swarm that may be related to a transform fault of the pre-Rodinia margin of protoLaurentia. Although the Alabama recess and Ouachita salient of the Pangaean Appalachian-Ouachita orogenic belt curve around the transform-rift margin of the Iapetan Ouachita embayment, the Bahamas transform of Atlantic opening follows the trace of the Iapetan Alabama-Oklahoma transform. Similarly, the Atlantic South Grand Banks transform follows the Iapetan Sept Isles transform, oblique to the Pangaean Appalachian orogenic belt in the Quebec salient. In contrast, both the Atlantic Bahamas transform and East Coast rift system cut obliquely across the Pangaean Suwannee-Wiggins suture, which, although it is the continental suture between Laurentia and the African sector of Gondwana, was not reactivated as the younger rift margin. At a smaller scale, however, the Suwannee-Wiggins suture was reactivated as the South Georgia basin, an intracratonic graben parallel with

  13. Bilateral sensorineural deafness and hydrocephalus due to foramen of Monro obstruction in sibs: A newly described autosomal recessive disorder

    SciTech Connect

    Chudley, A.E.; McCullough, C.; McCullough, D.W.

    1997-01-31

    We identified a Canadian-Mennonite family in which a brother and sister have hydrocephalus due to obstruction at the foramen of Monro and profound bilateral sensorineural deafness. This appears to be a unique combination of anomalies and, to our knowledge, has not been reported previously. Both parents and a brother are phenotypically normal. The parents are second cousins. Thus, on the basis of consanguinity, affected sibs of both sexes, and in the absence of evidence for intrauterine infections or other adverse perinatal events, this syndrome is likely inherited in an autosomal recessive fashion. 37 refs., 5 figs.

  14. Mitochondrial movement and inheritance in budding yeast.

    PubMed

    Boldogh, Istvan R; Fehrenbacher, Kammy L; Yang, Hyeong-Cheol; Pon, Liza A

    2005-07-18

    Mitochondria are essential organelles that perform fundamental cellular functions including aerobic energy mobilization, fatty acid oxidation, amino acid metabolism, heme biosynthesis and apoptosis. Mitochondria cannot be synthesized de novo. Therefore, the inheritance of this organelle is an essential part of the cell cycle; that is, daughter cells that do not inherit mitochondria will not survive. The budding yeast, Saccharomyces cerevisiae, is a facultative aerobe that can tolerate mitochondrial mutations that would be lethal in other organisms. Therefore, yeast has been used extensively to study inheritance and segregation of mitochondria. As a result, much of what we know regarding mitochondrial inheritance has been uncovered using yeast as a model system. Here, we describe the latest developments in mitochondrial motility and inheritance.

  15. Attitudes toward carrier screening and prenatal diagnosis for recessive hereditary deafness among the educated population in urban China.

    PubMed

    Fu, Xiaoli; Cai, Yi; Hu, Yechen; Liu, Jisheng; Yang, Tao

    2016-12-01

    Approximately 80% of hereditary deafness is recessive, in which case most mutation carriers were unaware of their carrier status. Though parental attitudes toward genetic testing and prenatal diagnosis are overall positive in those with deaf children, there is little information about that in the general population. To this end, we designed a self-completed questionnaire and distributed it in two colleges in Shanghai, China. A total of 975 completed surveys were returned in print or online forms. Our results showed that 98.7% of the respondents without family history of early onset deafness did not know or underestimated their likelihood to carry a recessive mutation in common deafness genes. After brief written information was given using GJB2, the most common recessive deafness gene as the example, 67.7% of the respondents expressed interest in knowing if they are carriers of GJB2 mutations through genetic testing. In hypothetical circumstance of carrying a recessive GJB2 mutation, 86.9% would suggest their partners to also take the test. In case that both were carriers, 88.7% would consider prenatal diagnosis and 80.7% would consider terminating an affected pregnancy. On the basis of these results, it was concluded that despite the poor awareness to the risk of recessive hereditary deafness, the majority of the educated population in urban China likely hold a positive view toward carrier screening and prenatal diagnosis of recessive deafness genes. © 2016 Wiley Periodicals, Inc.

  16. Familial pulmonary hypertension. Evidence of autosomal dominant inheritance.

    PubMed Central

    Thompson, P; McRae, C

    1970-01-01

    A patient with primary pulmonary hypertension is the fourth member of a family proven to have the disease. The patient's father married twice; the disease appeared in both families, and was transmitted through two generations. Multiple genetic and environmental factors may result in pulmonary hypertension, but the distribution of cases in this family and in others reported is consistent with the autosomal dominant inheritance of a single genetic trait. PMID:5212347

  17. Inherited disorders of blood coagulation.

    PubMed

    Lippi, Giuseppe; Franchini, Massimo; Montagnana, Martina; Favaloro, Emmanuel J

    2012-08-01

    Hemostasis is traditionally defined as a physiological response to blood vessel injury and bleeding, which entails a co-ordinated process involving the blood vessel, platelets, and blood clotting proteins (i.e. coagulation factors). Hemostasis can be divided into primary and secondary components. The former rapidly initiates after endothelial damage and is characterized by vascular contraction, platelet adhesion, and formation of a soft aggregate plug. The latter is initiated following the release of tissue factor and involves a complex sequence of events known as the blood coagulation cascade, encompassing serial steps where each coagulation factor activates another in a chain reaction that culminates in the conversion of fibrinogen to fibrin. Patients carrying abnormalities of the coagulation cascade (i.e. deficiencies of coagulation factors) have an increased bleeding tendency, where the clinical severity is mostly dependent upon the type and the plasma level of the factor affected. These disorders also impose a heavy medical and economic burden on individual patients and society in general. The aim of this article is to provide a general overview on the pathophysiology, clinics, diagnostics, and therapy of inherited disorders of coagulation factors.

  18. Paternity and inheritance of wealth

    NASA Astrophysics Data System (ADS)

    Hartung, John

    1981-06-01

    One of the oldest conjectures in anthropology is that men transfer wealth to their sister's son when the biological paternity of their `own' children is in doubt1-12. Because maternity is certain, a man is necessarily related to his sister's son and his brother (see Fig. 1). It is argued here that relatedness to male heirs can be assured by passing wealth to sister's sons or down a line of brothers, whether the prevailing kinship system reckons those brothers matrilineally or patrilineally. It is also argued that when several transfers of wealth are considered, a man's likelihood of being cuckolded need not be unrealistically high13 for his successive matrilineal heirs to be more related to him than his successive patrilineal heirs (see Fig. 2). Cross-cultural data on sister's son/brother inheritance14 and frequency of extramarital sex for females15 support the hypothesis that men tend to transmit wealth to their sister's son and/or brother when the probability that their putative children are their genetic children is relatively low.

  19. Leading the Team You Inherit.

    PubMed

    Watkins, Michael D

    2016-06-01

    Most leaders don't have the luxury of building their teams from scratch. Instead they're put in charge of an existing group, and they need guidance on the best way to take over and improve performance. Watkins, an expert on transitions, suggests a three-step approach: Assess. Act quickly to size up the personnel you've inherited, systematically gathering data from one-on-one chats, team meetings, and other sources. Reflect, too, on the business challenges you face, the kinds of people you want in various roles, and the degree to which they need to collaborate. Reshape. Adjust the makeup of the team by moving people to new positions, shifting their responsibilities, or replacing them. Make sure that everyone is aligned on goals and how to achieve them--you may need to change the team's stated direction. Consider also making changes in the way the team operates (reducing the frequency of meetings, for example, or creating new subteams). Then establish ground rules and processes to sustain desired behaviors, and revisit those periodically. Accelerate team development. Set your people up for some early wins. Initial successes will boost everyone's confidence and reinforce the value of your new operating model, thus paving the way for ongoing growth.

  20. Prediction of the start of next recession using latent factors

    NASA Astrophysics Data System (ADS)

    Pooi, Ah-Hin; Soo, Huei-Ching; Pan, Wei-Yeing

    2016-10-01

    The data on the binary recession variable and the latent factors extracted from a large set of economic variables are fitted with a multivariate power-normal distribution. A conditional distribution for the recession variable is obtained from the fitted multivariate distribution. The results based on the US economic data show that the 2.5% point of the conditional distribution provides a good indicator for the start of the next recession.

  1. Recessive Mutations in COL25A1 Are a Cause of Congenital Cranial Dysinnervation Disorder

    PubMed Central

    Shinwari, Jameela M.A.; Khan, Arif; Awad, Salma; Shinwari, Zakia; Alaiya, Ayodele; Alanazi, Mohamad; Tahir, Asma; Poizat, Coralie; Al Tassan, Nada

    2015-01-01

    Abnormal ocular motility is a common clinical feature in congenital cranial dysinnervation disorder (CCDD). To date, eight genes related to neuronal development have been associated with different CCDD phenotypes. By using linkage analysis, candidate gene screening, and exome sequencing, we identified three mutations in collagen, type XXV, alpha 1 (COL25A1) in individuals with autosomal-recessive inheritance of CCDD ophthalmic phenotypes. These mutations affected either stability or levels of the protein. We further detected altered levels of sAPP (neuronal protein involved in axon guidance and synaptogenesis) and TUBB3 (encoded by TUBB3, which is mutated in CFEOM3) as a result of null mutations in COL25A1. Our data suggest that lack of COL25A1 might interfere with molecular pathways involved in oculomotor neuron development, leading to CCDD phenotypes. PMID:25500261

  2. The DFNB1 subtype of autosomal recessive non-syndromic hearing impairment.

    PubMed

    del Castillo, Francisco J; del Castillo, Ignacio

    2011-06-01

    Inherited hearing impairment is a frequent and highly heterogeneous condition. Among the different subtypes of autosomal recessive non-syndromic hearing impairment, DFNB1 is remarkable for its high frequency in most populations. It is caused by mutations in the coding region or splice-sites of the GJB2 gene, or by mutations affecting regulatory sequences that are essential for the expression of this gene. GJB2 encodes connexin-26, a protein component of intercellular gap junctions, which play crucial physiological roles in the cochlea. Because of its high frequency, DFNB1 hearing impairment has received continued attention from researchers along the years, resulting in a wealth of data that is unparalleled among these disorders. Here we review our current knowledge on the genetic, molecular, and phenotypic aspects of this subtype of hearing impairment.

  3. New Recessive Syndrome of Microcephaly, Cerebellar Hypoplasia, and Congenital Heart Conduction Defect

    PubMed Central

    Zaki, Maha S; Salam, Ghada M H Abdel; Saleem, Sahar N; Dobyns, William B; Issa, Mahmoud Y; Sattar, Shifteh; Gleeson, Joseph G

    2011-01-01

    We identified a two-branch consanguineous family in which four affected members (three females and one male) presented with constitutive growth delay, severe psychomotor retardation, microcephaly, cerebellar hypoplasia, and second-degree heart block. They also shared distinct facial features and similar appearance of their hands and feet. Childhood-onset insulin-dependent diabetes mellitus developed in one affected child around the age of 9 years. Molecular analysis excluded mutations in potentially related genes such as PTF1A, EIF2AK3, EOMES, and WDR62. This condition appears to be unique of other known conditions, suggesting a unique clinical entity of autosomal recessive mode of inheritance. © 2011 Wiley Periodicals, Inc. PMID:22002884

  4. A visual basic spreadsheet macro for recession curve analysis.

    PubMed

    Posavec, Kristijan; Bacani, Andrea; Nakić, Zoran

    2006-01-01

    A Visual Basic program for an Excel spreadsheet was written to construct a master recession curve (MRC), using the adapted matching strip method, for recession analysis of ground water level time series. The program uses five different linear/nonlinear regression models to adjust individual recession segments to their proper positions in the MRC. The program can also be used to analyze the recession segments of other time series, such as daily stream discharge or stage. Some examples of field data from Croatia are used to illustrate the usefulness of its application.

  5. The role of genealogy and clinical family histories in documenting possible inheritance patterns for diabetes mellitus in the pre-insulin era: part 1. The clinical case of Josephine Imperato.

    PubMed

    Imperato, Pascal James; Imperato, Gavin H

    2009-10-01

    Establishing the role of heredity in type 2 diabetes mellitus (type 2 DM) is challenging. While type 2 DM frequently displays a pattern of familial aggregation, many other risk factors are responsible for the clinical expression of the disease. This paper reviews a number of the early twentieth-century studies of inheritance patterns for type 2 DM and presents in detail the history of Josephine Foniciello Imperato (Maria Giuseppa Foniciello) who died from the disease in New York City at the age of 52 years on 14 November 1921, ten months before commercial insulin became available.

  6. Single-gene speciation with pleiotropy: effects of allele dominance, population size, and delayed inheritance.

    PubMed

    Yamamichi, Masato; Sasaki, Akira

    2013-07-01

    Single-gene speciation is considered to be unlikely, but an excellent example is found in land snails, in which a gene for left-right reversal has given rise to new species multiple times. This reversal might be facilitated by their small population sizes and maternal effect (i.e., "delayed inheritance," in which an individual's phenotype is determined by the genotype of its mother). Recent evidence suggests that a pleiotropic effect of the speciation gene on antipredator survival may also promote speciation. Here we theoretically demonstrate that, without a pleiotropic effect, in small populations the fixation probability of a recessive mutant is higher than a dominant mutant, but they are identical for large populations and sufficiently weak selection. With a pleiotropic effect that increases mutant viability, a dominant mutant has a higher fixation probability if the strength of viability selection is sufficiently greater than that of reproductive incompatibility, whereas a recessive mutant has a higher fixation probability otherwise. Delayed inheritance increases the fixation probability of a mutant if viability selection is sufficiently weaker than reproductive incompatibility. Our results clarify the conflicting effects of viability selection and positive frequency-dependent selection due to reproductive incompatibility and provide a new perspective to single-gene speciation theory.

  7. [The decline in population growth, income distribution, and economic recession].

    PubMed

    Banguero, H

    1983-05-01

    This work uses Keynesian principles and an analysis of the Colombian population in the 1970s to argue that the Colombian policy of slowing population growth, which was adopted with the aim of improving the general welfare of the population, has had shortterm negative effects on effective demand and thus on the level of employment and welfare. These negative effects were caused by the inflexibility of income distribution, which prevented expansion of the internal market, complicated by the stagnant condition of the external sector and the budget deficit. The results of the Colombian case study demonstrate how the deceleration of population growth beginning in the 1960s had a significant impact on the levels of consumption and savings and on the patterns of consumption, leading to low levels of investment and little dynamism. Although the current Colombian economic recession is aggravated by contextual factors such as the world economic recession, the high cost of capital, the industrial recession, and declining food production among others, at the core of the crisis are longer term structural determinants such as the decline in the rate of population growth and the highly unequal distribution of income and wealth, which have contributed to a shrinking of the internal market for some types of goods. Given the unlikelihood of renewed rapid population growth, the Keynesian model suggests that the only alternative for increasing aggregate demand is state intervention through public spending and investment and reorientation of the financial system to achieve a dynamic redistribution of income. Based on these findings and on proposals of other analysts, a stragegy for revitalization is proposed which would imply a gradual income redistribution to allow increased consumption of mass produced goods by the low income groups. Direct consumption subsidies would be avoided because of their inflationary and import-expanding tendencies; rather, incentives and support would be

  8. Inherited abnormalities of skeletal development in sheep.

    PubMed

    Thompson, K G; Piripi, S A; Dittmer, K E

    2008-09-01

    Inherited diseases of the skeleton are reported less often in sheep than in most other domestic animal species but are likely to occur more frequently than the veterinary literature would suggest. Although most are lethal or semi-lethal, the gene frequency for some of these diseases has reached surprisingly high levels in defined populations, presumably due either to the founder effect or the presence of a selective advantage of heterozygous individuals. This article reviews the clinical characteristics, pathology, mode of inheritance and molecular basis of skeletal diseases known to have a genetic aetiology in sheep. Inherited skeletal diseases of sheep are potential models for studying the treatment of similar diseases in humans.

  9. [INHERITANCE OF EPIDERMIS PIGMENTATION IN SUNFLOWER ACHENES].

    PubMed

    Gorohivets, N A; Vedmedeva, E V

    2016-01-01

    Inheritance of epidermis pigmentation in the pericarp of sunflower seeds was studied. Inheritance of pigmentation was confirmed by three alleles Ew (epidermis devoid of pigmentation), Estr (epidermal pigmentation in strips), Edg (solid pigmentation). Dominance of the lack of epidermis pigmentation over striped epidermis and striped epidermis over solid pigmentation was established. It was shown that the striped epidermis pigmentation and the presence of testa layer are controlled by two genes, expression of which is independent from each other. Yellowish hypodermis was discovered in the sample I2K2218, which is inherited monogenically dominantly.

  10. Intimate Partner Violence in the Great Recession

    PubMed Central

    Schneider, Daniel; Harknett, Kristen; McLanahan, Sara

    2016-01-01

    In the United States, the Great Recession was marked by severe negative shocks to labor market conditions. In this study, we combine longitudinal data from the Fragile Families and Child Wellbeing Study with U.S. Bureau of Labor Statistics data on local area unemployment rates to examine the relationship between adverse labor market conditions and mothers' experiences of abusive behavior between 2001 and 2010. Unemployment and economic hardship at the household level were positively related to abusive behavior. Further, rapid increases in the unemployment rate increased men's controlling behavior toward romantic partners even after we adjust for unemployment and economic distress at the household level. We interpret these findings as demonstrating that the uncertainty and anticipatory anxiety that go along with sudden macroeconomic downturns have negative effects on relationship quality, above and beyond the effects of job loss and material hardship. PMID:27003136

  11. Did the Great Recession influence retirement plans?

    PubMed

    Szinovacz, Maximiliane E; Davey, Adam; Martin, Lauren

    2015-04-01

    The recent recession constitutes one of the macro forces that may have influenced workers' retirement plans. We evaluate a multilevel model that addresses the influence of macro-, meso-, and micro-level factors on retirement plans, changes in these plans, and expected retirement age. Using data from Waves 8 and 9 of the Health and Retirement Study (N=2,618), we find that individuals with defined benefit plans are more prone to change toward plans to stop work before the stock market declined, whereas the opposite trend holds for those without pensions. Debts, ability to reduce work hours, and firm unionization also influenced retirement plans. Findings suggest retirement planning education may be particularly important for workers without defined pensions, especially in times of economic volatility.

  12. Statistical tests for recessive lethal-carriers.

    PubMed

    Hamilton, M A; Haseman, J K

    1979-08-01

    This paper presents a statistical method for testing whether a male mouse is a recessive lethal-carrier. The analysis is based on a back-cross experiment in which the male mouse is mated with some of his daughters. The numbers of total implantations and intrauterine deaths in each litter are recorded. It is assumed that, conditional on the number of total implantations, the number of intrauterine deaths follows a binomial distribution. Using computer-simulated experimentation it is shown that the proposed statistical method, which is sensitive to the pattern of intrauterine death rates, is more powerful than a test based only on the total number of implant deaths. The proposed test requires relatively simple calculations and can be used for a wide range of values of total implantations and background implant mortality rates. For computer-simulated experiments, there was no practical difference between the empirical error rate and the nominal error rate.

  13. Inheritance of dense spike in diploid wheat and Aegilops squarrosa.

    PubMed

    Goncharov, N P; Kondratenko, E Ya; Kawahara, T

    2002-01-01

    The individuals of diploid wheat Triticum boeoticum, T. monococcum and T. sinskajae and goatgrass Aegilops squarrosa were picked out with screening the dense spike characteristics. The dense-spike accessions were discovered in diploid wheat (T. sinskajae) and Ae. squarrosa. Inheritance of the dense spike was studied. The trait was found to be controlled by a recessive gene in T. sinskajae and by an incomplete dominant gene in Ae. squarrosa. The dosage effect of dominant gene C was detected in interspecific pentaploid F1 hybrid plants T. compactum x T. palmovae (2n =35, A(u)A(b)BDD genome). The spike of pentaploid hybrid was not so dense as compared to hexaploid wheat T. compactum. This is the first report showing similarity of the expression of dominant gene C on D genome of the hexaploid wheat to that of dense spike gene in Ae. squarrosa. The existence of dense-spike accessions of Ae. squarrosa allows us to hypothesize that the origin of T. compactum is independent from that of common wheat.

  14. Candidate Genes for Inherited Autism Susceptibility in the Lebanese Population

    PubMed Central

    Kourtian, Silva; Soueid, Jihane; Makhoul, Nadine J.; Guisso, Dikran Richard; Chahrour, Maria; Boustany, Rose-Mary N.

    2017-01-01

    Autism spectrum disorder (ASD) is characterized by ritualistic-repetitive behaviors and impaired verbal/non-verbal communication. Many ASD susceptibility genes implicated in neuronal pathways/brain development have been identified. The Lebanese population is ideal for uncovering recessive genes because of shared ancestry and a high rate of consanguineous marriages. Aims here are to analyze for published ASD genes and uncover novel inherited ASD susceptibility genes specific to the Lebanese. We recruited 36 ASD families (ASD: 37, unaffected parents: 36, unaffected siblings: 33) and 100 unaffected Lebanese controls. Cytogenetics 2.7 M Microarrays/CytoScan™ HD arrays allowed mapping of homozygous regions of the genome. The CNTNAP2 gene was screened by Sanger sequencing. Homozygosity mapping uncovered DPP4, TRHR, and MLF1 as novel candidate susceptibility genes for ASD in the Lebanese. Sequencing of hot spot exons in CNTNAP2 led to discovery of a 5 bp insertion in 23/37 ASD patients. This mutation was present in unaffected family members and unaffected Lebanese controls. Although a slight increase in number was observed in ASD patients and family members compared to controls, there were no significant differences in allele frequencies between affecteds and controls (C/TTCTG: γ2 value = 0.014; p = 0.904). The CNTNAP2 polymorphism identified in this population, hence, is not linked to the ASD phenotype. PMID:28358038

  15. Temperature-sensitive yeast mutants defective in mitochondrial inheritance.

    PubMed

    McConnell, S J; Stewart, L C; Talin, A; Yaffe, M P

    1990-09-01

    The distribution of mitochondria to daughter cells is an essential feature of mitotic cell growth, yet the molecular mechanisms facilitating this mitochondrial inheritance are unknown. We have isolated mutants of Saccharomyces cerevisiae that are temperature-sensitive for the transfer of mitochondria into a growing bud. Two of these mutants contain single, recessive, nuclear mutations, mdm1 and mdm2, that cause temperature-sensitive growth and aberrant mitochondrial distribution at the nonpermissive temperature. The absence of mitochondria from the buds of mutant cells was confirmed by indirect immunofluorescence microscopy and by transmission electron microscopy. The mdm1 lesion also retards nuclear division and prevents the transfer of nuclei into the buds. Cells containing the mdm2 mutation grown at the nonpermissive temperature sequentially form multiple buds, each receiving a nucleus but no mitochondria. Neither mdm1 or mdm2 affects the transfer of vacuolar material into the buds or causes apparent changes in the tubulin- or actin-based cytoskeletons. The mdm1 and mdm2 mutations are cell-cycle specific, displaying an execution point in late G1 or early S phase.

  16. Anthocyanin inheritance and instability in purple basil (Ocimum basilicum L.).

    PubMed

    Phippen, W B; Simon, J E

    2000-01-01

    The instability of the purple pigments (anthocyanins) in purple basil varieties (Ocimum basilicum L.) limits their use as ornamental plants and as a potential anthocyanin source. Several self-pollinated generations of all purple plants were unsuccessful in stabilizing anthocyanin expression. In this study we investigated the inheritance and stability patterns of leaf traits using the Purple Ruffles variety. The results from the complete diallele crosses indicated anthocyanin expression in vegetative tissue is controlled by two dominant genes and ruffled leaf texture is controlled by a single recessive gene. Genes controlling leaf margin and leaf base structures were tightly linked to leaf texture. Essential oil production and oil constituents in leaves did not change as a result of the reversion in color. Color stability in cuttings was affected by the environment and the location where cuttings were taken. An accumulation of secondary metabolites (apigenin, genistein, and kaempferol) in green-reverted sectors on purple leaves was detected using reverse-phase high-performance liquid chromatography (HPLC) analysis; this suggested a potential block in the anthocyanin pathway. We hypothesize the reversion mutation is occurring in an anthocyanin regulatory gene.

  17. Inheritance of thelytoky in the honey bee Apis mellifera capensis.

    PubMed

    Chapman, N C; Beekman, M; Allsopp, M H; Rinderer, T E; Lim, J; Oxley, P R; Oldroyd, B P

    2015-06-01

    Asexual reproduction via thelytokous parthenogenesis is widespread in the Hymenoptera, but its genetic underpinnings have been described only twice. In the wasp Lysiphlebus fabarum and the Cape honey bee Apis mellifera capensis the origin of thelytoky have each been traced to a single recessive locus. In the Cape honey bee it has been argued that thelytoky (th) controls the thelytoky phenotype and that a deletion of 9 bp in the flanking intron downstream of exon 5 (tae) of the gemini gene switches parthenogenesis from arrhenotoky to thelytoky. To further explore the mode of inheritance of thelytoky, we generated reciprocal backcrosses between thelytokous A. m. capensis and the arrhenotokous A. m. scutellata. Ten genetic markers were used to identify 108 thelytokously produced offspring and 225 arrhenotokously produced offspring from 14 colonies. Patterns of appearance of thelytokous parthenogenesis were inconsistent with a single locus, either th or tae, controlling thelytoky. We further show that the 9 bp deletion is present in the arrhenotokous A. m. scutellata population in South Africa, in A. m. intermissa in Morocco and in Africanized bees from Brazil and Texas, USA, where thelytoky has not been reported. Thus the 9  p deletion cannot be the cause of thelytoky. Further, we found two novel tae alleles. One contains the previously described 9 bp deletion and an additional deletion of 7 bp nearby. The second carries a single base insertion with respect to the wild type. Our data are consistent with the putative th locus increasing reproductive capacity.

  18. Return to physical activity after gastrocnemius recession

    PubMed Central

    Tang Qian Ying, Camelia; Lai Wei Hong, Sean; Lee, Bing Howe; Thevendran, Gowreeson

    2016-01-01

    AIM To prospectively investigate the time taken and patients’ ability to resume preoperative level of physical activity after gastrocnemius recession. METHODS Endoscopic gastrocnemius recession (EGR) was performed on 48 feet in 46 consecutive sportspersons, with a minimum follow-up of 24 mo. The Halasi Ankle Activity Score was used to quantify the level of physical activity. Time taken to return to work and physical activity was recorded. Functional outcomes were evaluated using the short form 36 (SF-36), American Orthopedic Foot and Ankle Society (AOFAS) Hindfoot score and modified Olerud and Molander (O and M) scores respectively. Patient’s satisfaction and pain experienced were assessed using a modified Likert scale and visual analogue scales. P-value < 0.05 was considered statistically significant. RESULTS Ninety-one percent (n = 42) of all patients returned to their preoperative level of physical activity after EGR. The mean time for return to physical activity was 7.5 (2-24) mo. Ninety-eight percent (n = 45) of all patients were able to return to their preoperative employment status, with a mean time of 3.6 (1-12) mo. Ninety-six percent (n = 23) of all patients with an activity score > 2 were able to resume their preoperative level of physical activity in mean time of 8.8 mo, as compared to 86% (n = 19) of patients whose activity score was ≤ 2, with mean time of 6.1 mo. Significant improvements were noted in SF-36, AOFAS hindfoot and modified O and M scores. Ninety percent of all patients rated good or very good outcomes on the Likert scale. CONCLUSION The majority of patients were able to return to their pre-operative level of sporting activity after EGR. PMID:27900272

  19. A recessive Nav1.4 mutation underlies congenital myasthenic syndrome with periodic paralysis

    PubMed Central

    Habbout, Karima; Poulin, Hugo; Rivier, François; Giuliano, Serena; Sternberg, Damien; Fontaine, Bertrand; Eymard, Bruno; Morales, Raul Juntas; Echenne, Bernard; King, Louise; Hanna, Michael G.; Männikkö, Roope; Chahine, Mohamed; Nicole, Sophie

    2016-01-01

    Objective: To determine the molecular basis of a complex phenotype of congenital muscle weakness observed in an isolated but consanguineous patient. Methods: The proband was evaluated clinically and neurophysiologically over a period of 15 years. Genetic testing of candidate genes was performed. Functional characterization of the candidate mutation was done in mammalian cell background using whole cell patch clamp technique. Results: The proband had fatigable muscle weakness characteristic of congenital myasthenic syndrome with acute and reversible attacks of most severe muscle weakness as observed in periodic paralysis. We identified a novel homozygous SCN4A mutation (p.R1454W) linked to this recessively inherited phenotype. The p.R1454W substitution induced an important enhancement of fast and slow inactivation, a slower recovery for these inactivated states, and a frequency-dependent regulation of Nav1.4 channels in the heterologous expression system. Conclusion: We identified a novel loss-of-function mutation of Nav1.4 that leads to a recessive phenotype combining clinical symptoms and signs of congenital myasthenic syndrome and periodic paralysis, probably by decreasing channel availability for muscle action potential genesis at the neuromuscular junction and propagation along the sarcolemma. PMID:26659129

  20. Comprehensive Analysis of Deafness Genes in Families with Autosomal Recessive Nonsyndromic Hearing Loss

    PubMed Central

    Atik, Tahir; Onay, Huseyin; Aykut, Ayca; Bademci, Guney; Kirazli, Tayfun; Tekin, Mustafa; Ozkinay, Ferda

    2015-01-01

    Comprehensive genetic testing has the potential to become the standard of care for individuals with hearing loss. In this study, we investigated the genetic etiology of autosomal recessive nonsyndromic hearing loss (ARNSHL) in a Turkish cohort including individuals with cochlear implant, who had a pedigree suggestive of an autosomal recessive inheritance. A workflow including prescreening of GJB2 and a targeted next generation sequencing panel (Illumına TruSightTM Exome) covering 2761 genes that we briefly called as mendelian exome sequencing was used. This panel includes 102 deafness genes and a number of genes causing Mendelian disorders. Using this approach, we identified causative variants in 21 of 29 families. Three different GJB2 variants were present in seven families. Remaining 14 families had 15 different variants in other known NSHL genes (MYO7A, MYO15A, MARVELD2, TMIE, DFNB31, LOXHD1, GPSM2, TMC1, USH1G, CDH23). Of these variants, eight are novel. Mutation detection rate of our workflow is 72.4%, confirming the usefulness of targeted sequencing approach in NSHL. PMID:26561413

  1. A homozygous mutation in ADAMTSL4 causes autosomal-recessive isolated ectopia lentis.

    PubMed

    Ahram, Dina; Sato, T Shawn; Kohilan, Abdulghani; Tayeh, Marwan; Chen, Shan; Leal, Suzanne; Al-Salem, Mahmoud; El-Shanti, Hatem

    2009-02-01

    Ectopia lentis is a genetically heterogeneous condition that is characterized by the subluxation of the lens resulting from the disruption of the zonular fibers. Patients with ectopia lentis commonly present with a marked loss in visual acuity in addition to a number of possibly accompanying ocular complications including cataract, myopia, and retinal detachment. We here describe an isolated form of ectopia lentis in a large inbred family that shows autosomal-recessive inheritance. We map the ectopia lentis locus in this family to the pericentromeric region on chromosome 1 (1p13.2-q21.1). The linkage region contains well more than 60 genes. Mutation screening of four candidate genes revealed a homozygous nonsense mutation in exon 11 of ADAMTSL4 (p.Y595X; c.1785T-->G) in all affected individuals that is absent in 380 control chromosomes. The mutation would result in a truncated protein of half the original length, if the mRNA escapes nonsense-mediated decay. We conclude that mutations in ADAMTSL4 are responsible for autosomal-recessive simple ectopia lentis and that ADAMTS-like4 plays a role in the development and/or integrity of the zonular fibers.

  2. Comprehensive Analysis of Deafness Genes in Families with Autosomal Recessive Nonsyndromic Hearing Loss.

    PubMed

    Atik, Tahir; Onay, Huseyin; Aykut, Ayca; Bademci, Guney; Kirazli, Tayfun; Tekin, Mustafa; Ozkinay, Ferda

    2015-01-01

    Comprehensive genetic testing has the potential to become the standard of care for individuals with hearing loss. In this study, we investigated the genetic etiology of autosomal recessive nonsyndromic hearing loss (ARNSHL) in a Turkish cohort including individuals with cochlear implant, who had a pedigree suggestive of an autosomal recessive inheritance. A workflow including prescreening of GJB2 and a targeted next generation sequencing panel (Illumına TruSightTM Exome) covering 2761 genes that we briefly called as mendelian exome sequencing was used. This panel includes 102 deafness genes and a number of genes causing Mendelian disorders. Using this approach, we identified causative variants in 21 of 29 families. Three different GJB2 variants were present in seven families. Remaining 14 families had 15 different variants in other known NSHL genes (MYO7A, MYO15A, MARVELD2, TMIE, DFNB31, LOXHD1, GPSM2, TMC1, USH1G, CDH23). Of these variants, eight are novel. Mutation detection rate of our workflow is 72.4%, confirming the usefulness of targeted sequencing approach in NSHL.

  3. Short communication: Distribution of recessive genetic defect carriers in Chinese Holstein.

    PubMed

    Sun, D X; Fan, X H; Xie, Y; Chu, Q; Sun, Y; Zhang, Y; Zhang, S L; Gong, W J; Chen, S H; Li, Y H; Shi, W H; Zhang, Y

    2011-11-01

    In dairy cattle, 4 important recessive hereditary diseases exist: complex vertebral malformation (CVM), bovine leukocyte adhesion deficiency (BLAD), citrullinemia (CTLN), and deficiency of uridine monophosphate synthase (DUMPS). Holstein Associations in developed countries have established monitoring systems for such disorders in Holstein bulls for decades. Over the past decades, China has continuously imported Holstein semen and embryos, mainly from North America but also from Europe. The dissemination of such genetic defects was undetermined until now, although efforts were taken to develop molecular techniques and detect carriers for CVM and BLAD in small populations of Chinese dairy cattle. Thus, herein we extensively screened 732 proven bulls participating in artificial insemination programs and 136 young bulls entering progeny test from 15 bull stations in China for CVM, BLAD, CTLN, and DUMPS. The proportion of carriers of the defects was found to be 7.72, 1.38, 0.23, and 0.12%, respectively. Given our findings, early diagnostic and monitoring systems on recessive inherited disorders among proven and young bulls entering the national genetic improvement programs for dairy cattle of China should be established immediately, in which a series of measures will be taken to prevent further spreading of such disorders and gradually eliminate them in the dairy cattle population in China.

  4. Is autosomal recessive deafness associated with oculocutaneous albinism a "coincidence syndrome"?

    PubMed

    Lezirovitz, Karina; Nicastro, Fernanda Stávale; Pardono, Eliete; Abreu-Silva, Ronaldo Serafim; Batissoco, Ana Carla; Neustein, Isaac; Spinelli, Mauro; Mingroni-Netto, Regina Célia

    2006-01-01

    Hearing impairment is frequently found associated with pigmentary disorders in many syndromes. However, total oculocutaneous albinism (OCA) associated with deafness has been described only once, by Ziprkowski and Adam (Arch Dermatol 89:151-155, 1964) in an inbred family. A syndrome associating deafness and OCA was suggested by the authors, but two separate recessive genes segregating in this inbred group were also proposed later by Fraser (OMIM # 220900). Combined deafness and total OCA were also observed by us in a family originally reported to be nonconsanguineous but in which haplotyping showed evidence of a common ancestry: the proband was affected by both diseases, one of his sisters had only OCA and another sister had only deafness. Both the proband and his deaf sister were found to be homozygotes for the 35delG mutation (GJB2 gene), the most frequent cause of hereditary deafness. Linkage analysis with markers close to the four known OCA loci excluded linkage to OCA1, OCA2, and OCA3, and homozygosity in markers near OCA4 locus was observed. Sequencing of the corresponding gene (MATP) revealed a c.1121delT mutation, which leads to a stop codon at position 397 (L374fsX397). Clearly, the combined occurrence of deafness and albinism in this pedigree was due to mutations in two different genes, showing autosomal recessive inheritance. We speculate that the putative syndrome reported by Ziprkowski and Adam might have resulted from the co-occurrence of autosomal recessive deafness and albinism in the same pedigree, as suggested by Fraser.

  5. Inherited Representations are Read in Development

    PubMed Central

    Shea, Nicholas

    2013-01-01

    Recent theoretical work has identified a tightly constrained sense in which genes carry representational content. Representational properties of the genome are founded in the transmission of DNA over phylogenetic time and its role in natural selection. However, genetic representation is not just relevant to questions of selection and evolution. This article goes beyond existing treatments and argues for the heterodox view that information generated by a process of selection over phylogenetic time can be read in ontogenetic time, in the course of individual development. Recent results in evolutionary biology, drawn both from modelling work, and from experimental and observational data, support a role for genetic representation in explaining individual ontogeny: both genetic representations and environmental information are read by the mechanisms of development, in an individual, so as to lead to adaptive phenotypes. Furthermore, in some cases there appears to have been selection between individuals that rely to different degrees on the two sources of information. Thus, the theory of representation in inheritance systems like the genome is much more than just a coherent reconstruction of information talk in biology. Genetic representation is a property with considerable explanatory utility. 1 Introduction2 Inherited Representations3 Reading Genetic Representations   3.1 Do genes carry correlational information?4 Selection Between Genetic and Environmental Information   4.1 Modelling  4.2 Empirical applications  4.3 Maternal effects5 Genetic Representation and the Genome   5.1 Information capacity of organisms' genomes  5.2 Many amino acids, few nucleotides  5.3 A function of sex6 Explaining Further Aspects of Development   6.1 Canalization against environmental variation  6.2 An informational function for the nuclear membrane?7 Conclusion PMID:23526835

  6. Lamarck, Evolution, and the Inheritance of Acquired Characters

    PubMed Central

    Burkhardt, Richard W.

    2013-01-01

    Scientists are not always remembered for the ideas they cherished most. In the case of the French biologist Jean-Baptiste Lamarck, his name since the end of the nineteenth century has been tightly linked to the idea of the inheritance of acquired characters. This was indeed an idea that he endorsed, but he did not claim it as his own nor did he give it much thought. He took pride instead in advancing the ideas that (1) nature produced successively all the different forms of life on earth, and (2) environmentally induced behavioral changes lead the way in species change. This article surveys Lamarck’s ideas about organic change, identifies several ironies with respect to how his name is commonly remembered, and suggests that some historical justice might be done by using the adjective “Lamarckian” to denote something more (or other) than a belief in the inheritance of acquired characters. PMID:23908372

  7. An Update on Laboratory Diagnosis of Liver Inherited Diseases

    PubMed Central

    Elce, Ausilia; Amato, Felice

    2013-01-01

    Liver inherited diseases are a group of genetically determined clinical entities that appear with an early chronic liver involvement. They include Wilson's disease (hepatolenticular degeneration), hereditary hemochromatosis, and alpha-1-antitrypsin deficiency. In addition, cystic fibrosis, although it is not specifically a liver disease, may cause a severe liver involvement in a significant percentage of cases. For all these pathologies, the disease gene is known, and molecular analysis may contribute to the unequivocal diagnosis. This approach could avoid the patient invasive procedures and limit complications associated with a delay in diagnosis. We review liver inherited diseases on the basis of the genetic defect, focusing on the contribution of molecular analysis in the multistep diagnostic workup. PMID:24222913

  8. Developmental origins of epigenetic transgenerational inheritance.

    PubMed

    Hanson, Mark A; Skinner, Michael K

    Environmental factors can induce epigenetic alterations in the germ cells that can potentially be transmitted transgenerationally. This non-genetic form of inheritance is termed epigenetic transgenerational inheritance and has been shown in a variety of species including plants, flies, worms, fish, rodents, pigs, and humans. This phenomenon operates during specific critical windows of exposure, linked to the developmental biology of the germ cells (sperm and eggs). Therefore, concepts of the developmental origins of transgenerational inheritance of phenotypic variation and subsequent disease risk need to include epigenetic processes affecting the developmental biology of the germ cell. These developmental impacts on epigenetic transgenerational inheritance, in contrast to multigenerational exposures, are the focus of this Perspective.

  9. Developmental origins of epigenetic transgenerational inheritance

    PubMed Central

    Hanson, Mark A.; Skinner, Michael K.

    2016-01-01

    Environmental factors can induce epigenetic alterations in the germ cells that can potentially be transmitted transgenerationally. This non-genetic form of inheritance is termed epigenetic transgenerational inheritance and has been shown in a variety of species including plants, flies, worms, fish, rodents, pigs, and humans. This phenomenon operates during specific critical windows of exposure, linked to the developmental biology of the germ cells (sperm and eggs). Therefore, concepts of the developmental origins of transgenerational inheritance of phenotypic variation and subsequent disease risk need to include epigenetic processes affecting the developmental biology of the germ cell. These developmental impacts on epigenetic transgenerational inheritance, in contrast to multigenerational exposures, are the focus of this Perspective. PMID:27390622

  10. Genetic Testing for Inherited Heart Disease

    MedlinePlus

    ... of the American Heart Association Cardiology Patient Page Genetic Testing for Inherited Heart Disease Allison L. Cirino , ... for developing the family’s heart condition. What Is Genetic Testing and What Can it Tell Me? Genetic ...

  11. Center for Inherited Disease Research (CIDR)

    Cancer.gov

    The Center for Inherited Disease Research (CIDR) Program at The Johns Hopkins University provides high-quality next generation sequencing and genotyping services to investigators working to discover genes that contribute to common diseases.

  12. Inherited Disorders of Calcium and Phosphate Metabolism

    PubMed Central

    Gattineni, Jyothsna

    2014-01-01

    Purpose of Review Inherited disorders of calcium and phosphate homeostasis have variable presentation and can cause significant morbidity. Understanding the mode of inheritance and pathophysiology of these conditions will help in the diagnosis and early institution of therapy. Recent Findings Identification of genetic mutations in human subjects and animal models has advanced our understanding of many inherited disorders of calcium and phosphate regulation. Identification of mutations of CaSR also has improved our understanding of hypocalcemic and hypercalcemic conditions. Mutations of Fgf23, Klotho and phosphate transporter genes have been identified as causes for disorders of phosphate metabolism. Summary Calcium and phosphate homeostasis is tightly regulated in a narrow range due to their vital role in many biological processes. Inherited disorders of calcium and phosphate metabolism though uncommon can have severe morbidity. Genetic counseling of the affected families is an important part of the follow up of these patients. PMID:24553630

  13. Children's Recess Physical Activity: Movement Patterns and Preferences

    ERIC Educational Resources Information Center

    Woods, Amelia Mays; Graber, Kim C.; Daum, David Newman

    2012-01-01

    The benefits of recess can be reaped by all students regardless of socioeconomic status, race, or gender and at relatively little cost. The purpose of this study was to examine physical activity (PA) variables related to the recess PA patterns of third and fourth grade children and the social preferences and individuals influencing their PA…

  14. Recess Physical Activity Packs in Elementary Schools: A Qualitative Investigation

    ERIC Educational Resources Information Center

    Elliott, Steven; Combs, Sue; Boyce, Robert

    2011-01-01

    To supplement the present weekly allotment of 30 minutes of physical education, a school district in southeastern North Carolina identified recess time as part of the state mandated (HSP-S-000) 150 minutes of physical activity (PA) per week and have purchased fitness equipment (recess packs) for the children to use. Twelve participants were…

  15. Physical Education and Recess Contributions to Sixth Graders' Physical Activity

    ERIC Educational Resources Information Center

    Gutierrez, Ashley A.; Williams, Skip M.; Coleman, Margaret M.; Garrahy, Deborah A.; Laurson, Kelly R.

    2016-01-01

    Background: The purpose of this study was twofold: (a) to examine the percentage of the daily threshold (12,000 steps) that physical education (PE) class and recess contribute to 6th grade students' overall daily physical activity (PA) and (b) to examine the relationships between gender, PA outside of school, BMI, and steps during both recess and…

  16. Children's Physical Activity Levels during Indoor Recess Dance Videos

    ERIC Educational Resources Information Center

    Erwin, Heather; Koufoudakis, Ryann; Beighle, Aaron

    2013-01-01

    Background: Children's physical activity (PA) levels remain low, and schools are being asked to assume a leadership role in PA promotion. Research suggests outdoor recess contributes to children's overall PA levels. However, similar research is not available for indoor recess, which occurs frequently due to a variety of factors. The purpose of…

  17. Withholding Recess from Elementary School Students: Policies Matter

    ERIC Educational Resources Information Center

    Turner, Lindsey; Chriqui, Jamie F.; Chaloupka, Frank J.

    2013-01-01

    Background: Recess is a key aspect of a healthy elementary school environment and helps to keep students physically active during the school day. Although national organizations recommend that students not be withheld from recess, this practice occurs in schools. This study examined whether district policies were associated with school practices…

  18. Who Suffers during Recessions? NBER Working Paper No. 17951

    ERIC Educational Resources Information Center

    Hoynes, Hilary W.; Miller, Douglas L.; Schaller, Jessamyn

    2012-01-01

    In this paper we examine how business cycles affect labor market outcomes in the United States. We conduct a detailed analysis of how cycles affect outcomes differentially across persons of differing age, education, race, and gender, and we compare the cyclical sensitivity during the Great Recession to that in the early 1980s recession. We present…

  19. American undergraduate students' value development during the Great Recession.

    PubMed

    Park, Heejung; Twenge, Jean M; Greenfield, Patricia M

    2017-02-01

    The Great Recession's influence on American undergraduate students' values was examined, testing Greenfield's and Kasser's theories concerning value development during economic downturns. Study 1 utilised aggregate-level data to investigate (a) population-level value changes between the pre-recession (2004-2006: n = 824,603) and recession freshman cohort (2008-2010: n = 662,262) and (b) overall associations of population-level values with national economic climates over long-term periods by correlating unemployment rates and concurrent aggregate-level values across 1966-2015 (n = 10 million). Study 2 examined individual-level longitudinal value development from freshman to senior year, and whether the developmental trajectories differed between those who completed undergraduate education before the Great Recession (freshmen in 2002, n = 12,792) versus those who encountered the Great Recession during undergraduate years (freshmen in 2006, n = 13,358). Results suggest American undergraduate students' increased communitarianism (supporting Greenfield) and materialism (supporting Kasser) during the Great Recession. The recession also appears to have slowed university students' development of positive self-views. Results contribute to the limited literature on the Great Recession's influence on young people's values. They also offer theoretical and practical implications, as values of this privileged group of young adults are important shapers of societal values, decisions, and policies.

  20. The Impact of the Recession on College Students

    ERIC Educational Resources Information Center

    Berg-Cross, Linda; Green, Rodney

    2010-01-01

    This article had three goals: (a) to provide a brief economic review of the relationship between recessionary times, institutional reactions, and the life trajectory of recession-era college students; (b) to discuss the recession-related psychosocial stressors facing today's college students; and (c) to discuss how counseling centers can help…

  1. Patterns of inheritance in familial ALS.

    PubMed

    Bradley, Marcus; Bradley, Lloyd; de Belleroche, Jackie; Orrell, Richard W

    2005-05-10

    We investigated 185 families with ALS for evidence of anticipation and mitochondrial inheritance. Although initial analysis demonstrated significant anticipation of age at death between generations in patients with familial ALS, further analysis demonstrated features of regression to the mean, suggesting that the perceived differences are the result of bias. In addition, there was no evidence of an effect of preferential maternal inheritance, which would have supported transmission of mitochondrial DNA mutations.

  2. Inferior Oblique Weakening and Abnormal Head Position: Controlled Myotomy versus Recession

    PubMed Central

    Migliorini, R.; Malagola, R.; Comberiati, A. M.

    2016-01-01

    Purpose. Randomized controlled trial aimed at comparing surgical outcomes in a group of patients suffering from hyperfunction of the inferior oblique (IO) muscle with abnormal head position (AHP). The surgical techniques being compared are Recession and (thread) Controlled Myotomy. Materials and Methods. The group of 20 patients suffering from medium-high hyperfunction of the IO was assessed through an ophthalmological and orthoptic examination. 10 patients underwent traditional Recession (Group  A) and 10 were treated with Controlled Myotomy (Group  B). Results. The average age was 19 years ± 10.7 SD. After 1 year, 20% of Group  A showed a small Vertical Deviation associated with a small AHP, while 80% had orthophoria and 40% of them had a small AHP. 80% of Group  B showed a small Vertical Deviation associated with an equally small AHP, while 20% had orthophoria with a full resolution of AHP. Conclusion. Based on the results obtained and the fewer intrasurgical risks involved, thread Controlled Myotomy proved to be a valid alternative to Recession. Furthermore, in case of Recession, over the long period a small residual AHP remained in the patients who had orthophoria, unlike Myotomy which led to a total resolution. PMID:28018670

  3. Stability with Inheritance in the Conditional Strategy.

    PubMed

    Gross; Repka

    1998-06-21

    The conditional strategy is a theoretical framework that explains the existence within populations of individuals that express alternative behavioral, physical or life history tactics (phenotypes). An example is fighters and sneakers in many animal mating systems. In the conditional strategy the alternative tactics are chosen by individuals based on their state, for example large or small bodied. Since state is often heritable, due for example to additive genetic variance, the alternative tactics may also have inheritance. As the tactics do not have equal fitnesses, it is generally believed that any such inheritance would prevent the evolutionary stability of the conditional strategy. However, in previous work we introduced an Inheritance Theorem and were able to prove that a conditional strategy with tactic inheritances can have a unique equilibrium proportion of the tactics. We now prove a second property of our Inheritance Theorem, namely the stability of the equilibrium. This means that if the tactics are perturbed from their equilibrium proportions, they will return across generations to their equilibrium proportions. An example is provided in mites. We have therefore established an Inheritance Theorem which includes both the existence of an equilibrium and its stability for alternative tactics in a conditional strategy.Copyright 1998 Academic Press Limited

  4. Chromatin resetting mechanisms preventing transgenerational inheritance of epigenetic states.

    PubMed

    Iwasaki, Mayumi

    2015-01-01

    Epigenetic regulation can be altered by environmental cues including abiotic and biotic stresses. In most cases, environmentally-induced epigenetic changes are transient, but in some cases they are maintained for extensive periods of time and may even be transmitted to the next generation. However, the underlying mechanisms of transgenerational transmission of environmentally-induced epigenetic states remain largely unknown. Such traits can be adaptive, but also can have negative consequences if the parentally inherited epigenetic memory interferes with canonical environmental responses of the progeny. This review highlights recent insights into the mechanisms preventing transgenerational transmission of environmentally-induced epigenetic states in plants, which resemble those of germline reprogramming in mammals.

  5. Dominant and recessive central core disease associated with RYR1 mutations and fetal akinesia.

    PubMed

    Romero, Norma Beatriz; Monnier, Nicole; Viollet, Louis; Cortey, Anne; Chevallay, Martine; Leroy, Jean Paul; Lunardi, Joël; Fardeau, Michel

    2003-11-01

    We studied seven patients (fetuses/infants) from six unrelated families affected by central core disease (CCD) and presenting with a fetal akinesia syndrome. Two fetuses died before birth (at 31 and 32 weeks) and five infants presented severe symptoms at birth (multiple arthrogryposis, congenital dislocation of the hips, severe hypotonia and hypotrophy, skeletal and feet deformities, kyphoscoliosis, etc.). Histochemical and ultrastructural studies of muscle biopsies confirmed the diagnosis of CCD showing unique large eccentric cores. Molecular genetic investigations led to the identification of mutations in the ryanodine receptor (RYR1) gene in three families, two with autosomal recessive (AR) and one with autosomal dominant (AD) inheritance. RYR1 gene mutations were located in the C-terminal domain in two families (AR and AD) and in the N-terminal domain of the third one (AR). This is the first report of mutations in the RYR1 gene involved in a severe form of CCD presenting as a fetal akinesia syndrome with AD and AR inheritances.

  6. Preclinical studies on specific gene therapy for recessive retinal degenerative diseases.

    PubMed

    Stieger, Knut; Chauveau, Christine; Rolling, Fabienne

    2010-10-01

    Inherited retinal diseases are non-lethal and have a wide level of genetic heterogeneity. Many of the genes involved have now been identified and their function elucidated, providing a major step towards the development of gene-based treatments. The most widely used vectors for ocular gene delivery are based on adeno-associated virus (AAV) because they mediate long-term transgene expression in a variety of retinal cell types and elicit minimal immune responses. Extensive preclinical evaluation of gene transfer strategies in small and large animal models is key to the development of successful gene-based therapies for the retina. These preclinical studies have already allowed the field to reach the point where gene therapy to treat inherited blindness has been brought to clinical trial. In this manuscript, we focus on recombinant AAV-mediated specific gene therapy for recessive retinal degenerative diseases we describe the preclinical studies for the treatment of retinal degeneration caused by retinal pigmented epithelium (RPE) cells or photoreceptor defects and the immune response induced by retinal rAAV gene transfer.

  7. Novel and emerging therapies in the treatment of recessive dystrophic epidermolysis bullosa

    PubMed Central

    Rashidghamat, Ellie; McGrath, John A.

    2017-01-01

    Summary Epidermolysis bullosa (EB) is a clinically and genetically heterogeneous group of inherited blistering diseases that affects ∼ 500,000 people worldwide. Clinically, individuals with EB have fragile skin and are susceptible to blistering following minimal trauma, with mucous membrane and other organ involvement in some subtypes. Within the spectrum of EB, ∼ 5% of affected individuals have the clinically more severe recessive dystrophic (RDEB) variant with a prevalence of 8 per one million of the population. RDEB is caused by loss-of-function mutations in the type VII collagen gene, COL7A1, which leads to reduced or absent type VII collagen (C7) and a paucity of structurally effective anchoring fibrils at the dermal-epidermal junction (DEJ). Currently, there is no cure for RDEB, although considerable progress has been made in testing novel treatments including gene therapy (lentiviral and gamma retroviral vectors for COL7A1 supplementation in keratinocytes and fibroblasts), as well as cell therapy (use of allogeneic fibroblasts, mesenchymal stromal cells (MSCs), and bone marrow transplantation (BMT)). Here, we review current treatment modalities available as well as novel and emerging therapies in the treatment of RDEB. Clinical trials of new translational therapies in RDEB offer hope for improved clinical management of patients as well as generating broader lessons for regenerative medicine that could be applicable to other inherited or acquired abnormalities of wound healing or scarring. PMID:28357176

  8. Defective pro alpha 2(I) collagen synthesis in a recessive mutation in mice: a model of human osteogenesis imperfecta.

    PubMed Central

    Chipman, S D; Sweet, H O; McBride, D J; Davisson, M T; Marks, S C; Shuldiner, A R; Wenstrup, R J; Rowe, D W; Shapiro, J R

    1993-01-01

    Osteogenesis imperfecta (OI) is a heritable disorder of connective tissue associated with fractures, osteopenia, and short stature. OI results from mutations affecting the pro alpha 1 or pro alpha 2 gene of type I collagen. We describe a strain of mice with a nonlethal recessively inherited mutation (oim) that results in phenotypic and biochemical features that simulate moderate to severe human OI. The phenotype of homozygous oim mice includes skeletal fractures, limb deformities, generalized osteopenia, and small body size. Their femurs are smaller and demonstrate marked cortical thinning and fewer medullary trabeculae than those of wild-type mice. Breeding studies show the mutation is inherited in most crosses as a single recessive gene on chromosome 6, near the murine Cola-2 gene. Biochemical analysis of skin and bone, as well as isolated dermal fibroblast cultures, demonstrate that alpha 1(I) homotrimeric collagen accumulates in these tissues and is secreted by fibroblasts. Short labeling studies in fibroblasts demonstrate an absence of pro alpha 2(I) collagen chains. Nucleotide sequencing of the cDNA encoding the COOH-propeptide reveals a G deletion at pro alpha 2(I) nucleotide 3983; this results in an alteration of the sequence of the last 48 amino acids. The oim mouse will facilitate the study of type I collagen-related skeletal disease. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8446583

  9. Frontorhiny, a Distinctive Presentation of Frontonasal Dysplasia Caused by Recessive Mutations in the ALX3 Homeobox Gene

    PubMed Central

    Twigg, Stephen R.F.; Versnel, Sarah L.; Nürnberg, Gudrun; Lees, Melissa M.; Bhat, Meenakshi; Hammond, Peter; Hennekam, Raoul C.M.; Hoogeboom, A. Jeannette M.; Hurst, Jane A.; Johnson, David; Robinson, Alexis A.; Scambler, Peter J.; Gerrelli, Dianne; Nürnberg, Peter; Mathijssen, Irene M.J.; Wilkie, Andrew O.M.

    2009-01-01

    We describe a recessively inherited frontonasal malformation characterized by a distinctive facial appearance, with hypertelorism, wide nasal bridge, short nasal ridge, bifid nasal tip, broad columella, widely separated slit-like nares, long philtrum with prominent bilateral swellings, and midline notch in the upper lip and alveolus. Additional recurrent features present in a minority of individuals have been upper eyelid ptosis and midline dermoid cysts of craniofacial structures. Assuming recessive inheritance, we mapped the locus in three families to chromosome 1 and identified mutations in ALX3, which is located at band 1p13.3 and encodes the aristaless-related ALX homeobox 3 transcription factor. In total, we identified seven different homozygous pathogenic mutations in seven families. These mutations comprise missense substitutions at critical positions within the conserved homeodomain as well as nonsense, frameshift, and splice-site mutations, all predicting severe or complete loss of function. Our findings contrast with previous studies of the orthologous murine gene, which showed no phenotype in Alx3−/− homozygotes, apparently as a result of functional redundancy with the paralogous Alx4 gene. We conclude that ALX3 is essential for normal facial development in humans and that deficiency causes a clinically recognizable phenotype, which we term frontorhiny. PMID:19409524

  10. Whole Genome Sequencing Identifies Novel Compound Heterozygous Lysosomal Trafficking Regulator Gene Mutations Associated with Autosomal Recessive Chediak-Higashi Syndrome

    PubMed Central

    Jin, Yaqiong; Zhang, Li; Wang, Senfen; Chen, Feng; Gu, Yang; Hong, Enyu; Yu, Yongbo; Ni, Xin; Guo, Yongli; Shi, Tieliu; Xu, Zigang

    2017-01-01

    Chediak–Higashi syndrome (CHS) is a rare autosomal recessive disease characterized by varying degrees of oculocutaneous albinism, recurrent infections, and a mild bleeding tendency, with late neurologic dysfunction. This syndrome is molecularly characterized by pathognomonic mutations in the LYST (lysosomal trafficking regulator). Using whole genome sequencing (WGS) we attempted to identify novel mutations of CHS based on a family of CHS with atypical symptoms. The two patients demonstrated a phenotypic constellation including partial oculocutaneous albinism, frequency upper respiratory infection or a marginal intelligence, without bleeding tendency and severe immunodeficiency. WGS revealed two compound LYST mutations including a maternally inherited chr1:235969126G > A (rs80338652) and a novel paternally inherited chr1: 235915327A > AT, associated with autosomal recessive CHS. These two variants fall in the coding regions of LYST, resulting in premature truncation of LYST due to R1104X/N2535KfsX2 induced incomplete translation. Notably, the heterozygous carriers (i.e. parents) were unaffected. Our finding also reveals decreased plasma serotonin levels in patients with CHS compared with unaffected individuals for the first time. The present study contributes to improved understanding of the causes of this disease and provides new ideas for possible treatments. PMID:28145517

  11. Health in financial crises: economic recession and tuberculosis in Central and Eastern Europe.

    PubMed

    Arinaminpathy, Nimalan; Dye, Christopher

    2010-11-06

    The ongoing global financial crisis, which began in 2007, has drawn attention to the effect of declining economic conditions on public health. A quantitative analysis of previous events can offer insights into the potential health effects of economic decline. In the early 1990s, widespread recession across Central and Eastern Europe accompanied the collapse of the Soviet Union. At the same time, despite previously falling tuberculosis (TB) incidence in most countries, there was an upsurge of TB cases and deaths throughout the region. Here, we study the quantitative relationship between the lost economic productivity and excess TB cases and mortality. We use the data of the World Health Organization for TB notifications and deaths from 1980 to 2006, and World Bank data for gross domestic product. Comparing 15 countries for which sufficient data exist, we find strong linear associations between the lost economic productivity over the period of recession for each country and excess numbers of TB cases (r(2) = 0.94, p < 0.001) and deaths (r(2) = 0.94, p < 0.001) over the same period. If TB epidemiology and control are linked to economies in 2009 as they were in 1991 then the Baltic states, particularly Latvia, are now vulnerable to another upturn in TB cases and deaths. These projections are in accordance with emerging data on drug consumption, which indicate that these countries have undergone the greatest reductions since the beginning of 2008. We recommend close surveillance and monitoring during the current recession, especially in the Baltic states.

  12. Cultural transmission of a sign language when deafness is caused by recessive alleles at two independent loci.

    PubMed

    Aoki, K; Feldman, M W

    1994-02-01

    Two unlinked autosomal loci are assumed to affect the ability to hear in such a way that homozygosity for the recessive allele at either locus causes deafness. The five deaf genotypes are subject to the same negative selection due to a lower likelihood of marriage, but unmarried deaf persons remain socially active and participate in the cultural transmission of sign languages. Marriages are assortative for deafness or for hearing, and mutation occurs irreversibly from the dominant to recessive allele at each locus at the same rate. At mutation-selection balance, the fully polymorphic equilibrium is symmetrical. Based on this genetic model, we consider the relative importance of various forms of cultural transmission as they affect the persistence of sign languages. Horizontal transmission is shown to be effective when deaf children are able to interact with many peers. This observation is especially pertinent if assortative meeting of deaf children occurs, for example, at schools for the deaf. Oblique transmission can also be effective, but the literature suggests that this kind of transmission plays only a minor role. It is necessary, however, that some form of cultural transmission occur between generations. Thus, vertical transmission is a critical factor, despite the fact that parent-child transmission is often interrupted due to the recessive inheritance of deafness. In particular, the contribution of vertical transmission is enhanced by assortative mating for deafness.

  13. Rare variants in the notch signaling pathway describe a novel type of autosomal recessive Klippel-Feil syndrome.

    PubMed

    Karaca, Ender; Yuregir, Ozge O; Bozdogan, Sevcan T; Aslan, Huseyin; Pehlivan, Davut; Jhangiani, Shalini N; Akdemir, Zeynep C; Gambin, Tomasz; Bayram, Yavuz; Atik, Mehmed M; Erdin, Serkan; Muzny, Donna; Gibbs, Richard A; Lupski, James R

    2015-11-01

    Klippel-Feil syndrome is a rare disorder represented by a subgroup of segmentation defects of the vertebrae and characterized by fusion of the cervical vertebrae, low posterior hairline, and short neck with limited motion. Both autosomal dominant and recessive inheritance patterns were reported in families with Klippel-Feil. Mutated genes for both dominant (GDF6 and GDF3) and recessive (MEOX1) forms of Klippel-Feil syndrome have been shown to be involved in somite development via transcription regulation and signaling pathways. Heterotaxy arises from defects in proteins that function in the development of left-right asymmetry of the developing embryo. We describe a consanguineous family with a male proband who presents with classical Klippel-Feil syndrome together with heterotaxy (situs inversus totalis). The present patient also had Sprengel's deformity, deformity of the sternum, and a solitary kidney. Using exome sequencing, we identified a homozygous frameshift mutation (c.299delT; p.L100fs) in RIPPLY2, a gene shown to play a crucial role in somitogenesis and participate in the Notch signaling pathway via negatively regulating Tbx6. Our data confirm RIPPLY2 as a novel gene for autosomal recessive Klippel-Feil syndrome, and in addition-from a mechanistic standpoint-suggest the possibility that mutations in RIPPLY2 could also lead to heterotaxy. © 2015 Wiley Periodicals, Inc.

  14. Rare Variants in the Notch Signaling Pathway Describe a Novel Type of Autosomal Recessive Klippel–Feil Syndrome

    PubMed Central

    Karaca, Ender; Yuregir, Ozge O.; Bozdogan, Sevcan T.; Aslan, Huseyin; Pehlivan, Davut; Jhangiani, Shalini N.; Akdemir, Zeynep C.; Gambin, Tomasz; Bayram, Yavuz; Atik, Mehmed M.; Erdin, Serkan; Muzny, Donna; Gibbs, Richard A.; Lupski, James R.

    2016-01-01

    Klippel–Feil syndrome is a rare disorder represented by a subgroup of segmentation defects of the vertebrae and characterized by fusion of the cervical vertebrae, low posterior hairline, and short neck with limited motion. Both autosomal dominant and recessive inheritance patterns were reported in families with Klippel–Feil. Mutated genes for both dominant (GDF6 and GDF3) and recessive (MEOX1) forms of Klippel–Feil syndrome have been shown to be involved in somite development via transcription regulation and signaling pathways. Heterotaxy arises from defects in proteins that function in the development of left–right asymmetry of the developing embryo. We describe a consanguineous family with a male proband who presents with classical Klippel–Feil syndrome together with heterotaxy (situs inversus totalis). The present patient also had Sprengel’s deformity, deformity of the sternum, and a solitary kidney. Using exome sequencing, we identified a homozygous frameshift mutation (c.299delT; p.L100fs) in RIPPLY2, a gene shown to play a crucial role in somitogenesis and participate in the Notch signaling pathway via negatively regulating Tbx6. Our data confirm RIPPLY2 as a novel gene for autosomal recessive Klippel–Feil syndrome, and in addition—from a mechanistic standpoint—suggest the possibility that mutations in RIPPLY2 could also lead to heterotaxy. PMID:26238661

  15. A POU3F4 Mutation Causes Nonsyndromic Hearing Loss in a Chinese X-linked Recessive Family

    PubMed Central

    Du, Wan; Han, Ming-Kun; Wang, Da-Yong; Han, Bing; Zong, Liang; Lan, Lan; Yang, Ju; Shen, Qi; Xie, Lin-Yi; Yu, Lan; Guan, Jing; Wang, Qiu-Ju

    2017-01-01

    Background: The molecular genetic research showed the association between X-linked hearing loss and mutations in POU3F4. This research aimed to identify a POU3F4 mutation in a nonsyndromic X-linked recessive hearing loss family. Methods: A series of clinical evaluations including medical history, otologic examinations, family history, audiologic testing, and a high-resolution computed tomography scan were performed for each patient. Bidirectional sequencing was carried out for all polymerase chain reaction products of the samples. Moreover, 834 controls with normal hearing were also tested. Results: The pedigree showed X-linkage recessive inheritance pattern, and pathogenic mutation (c.499C>T) was identified in the proband and his family member, which led to a premature termination prior to the entire POU domains. This mutation co-segregated with hearing loss in this family. No mutation of POU3F4 gene was found in 834 controls. Conclusions: A nonsense mutation is identified in a family displaying the pedigree consistent with X-linked recessive pattern in POU3F4 gene. In addition, we may provide molecular diagnosis and genetic counseling for this family. PMID:28051029

  16. Autosomal recessive Stickler syndrome due to a loss of function mutation in the COL9A3 gene.

    PubMed

    Faletra, Flavio; D'Adamo, Adamo P; Bruno, Irene; Athanasakis, Emmanouil; Biskup, Saskia; Esposito, Laura; Gasparini, Paolo

    2014-01-01

    Stickler syndrome (STL) is a clinically variable and genetically heterogeneous syndrome characterized by ophthalmic, articular, orofacial, and auditory manifestations. STL has been described with both autosomal dominant and recessive inheritance. The dominant form is caused by mutations of COL2A1 (STL 1, OMIM 108300), COL11A1 (STL 2, OMIM 604841), and COL11A2 (STL 3, OMIM 184840) genes, while recessive forms have been associated with mutations of COL9A1 (OMIM 120210) and COL9A2 (OMIM 120260) genes. Type IX collagen is a heterotrimeric molecule formed by three genetically distinct chains: α1, α2, and α3 encoded by the COL9A1, COL9A2, and COL9A3 genes. Up to this time, only heterozygous mutations of COL9A3 gene have been reported in human and related to: (1) multiple epiphyseal dysplasia type 3, (2) susceptibility to an intervertebral disc disease, and (3) hearing loss. Here, we describe the first autosomal recessive Stickler family due to loss of function mutations (c.1176_1198del, p.Gln393Cysfs*25) of COL9A3 gene. These findings extend further the role of collagen genes family in the disease pathogenesis.

  17. Novel and novel de novo mutations in NTRK1 associated with congenital insensitivity to pain with anhidrosis: a case report.

    PubMed

    Wang, Qingli; Guo, Shanna; Duan, Guangyou; Xiang, Guifang; Ying, Ying; Zhang, Yuhao; Zhang, Xianwei

    2015-05-01

    Congenital insensitivity to pain with anhidrosis (CIPA) is a very rare autosomal recessively inherited disorder. The main clinical features of the disorder consist of absence of reactions to noxious stimuli and inability to sweat under any conditions.In this case report, a 3-year-old Chinese boy diagnosed with CIPA presented with the core features of CIPA, including insensitivity to noxious stimuli, self-mutilation, inability to sweat, and developmental delay. Clinical and genetic analyses were conducted on the affected boy.Sequencing analysis revealed an inherited novel mutation, c.1635G>C, and a novel de novo mutation, c.2197G>A, in the NTRK1 gene. In silico studies suggested that the mutations described are detrimental to the function of the protein encoded by the NTRK1 gene.The two novel mutations described here widen the genetic spectrum of CIPA, and this knowledge will benefit studies addressing this disease and pain medicine in the future.

  18. Highly consistent patterns for inherited human diseases at the molecular level.

    PubMed

    López-Bigas, Núria; Blencowe, Benjamin J; Ouzounis, Christos A

    2006-02-01

    Over 1600 mammalian genes are known to cause an inherited disorder, when subjected to one or more mutations. These disease genes represent a unique resource for the identification and quantification of relationships between phenotypic attributes of a disease and the molecular features of the associated disease genes, including their ascribed annotated functional classes and expression patterns. Such analyses can provide a more global perspective and a deeper understanding of the probable causes underlying human hereditary diseases. In this perspective and critical view of disease genomics, we present a comparative analysis of genes reported to cause inherited diseases in humans in terms of their causative effects on physiology, their genetics and inheritance modes, the functional processes they are involved in and their expression profiles across a wide spectrum of tissues. Our analysis reveals that there are more extensive correlations between these attributes of genetic disease genes than previously appreciated. For instance, the functional pattern of genes causing dominant and recessive diseases is markedly different. Also, the function of the genes and their expression correlate with the type of disease they cause when mutated. The results further indicate that a comparative genomics approach for the analysis of genes linked to human genetic diseases will facilitate the elucidation of the underlying molecular and cellular mechanisms.

  19. Inheritance of the general shell color in the scallop Argopecten purpuratus (Bivalvia: Pectinidae).

    PubMed

    Winkler, F M; Estévez, B F; Jollán, L B; Garrido, J P

    2001-01-01

    Although some external coloration and pigmentation patterns in molluscan shells may be attributable to environmental factors, most variation in these phenotypic characters depends on uncomplicated genetic mechanisms. Genetic research on inheritance of color variations in the north-Chilean scallop (Argopecten purpuratus) has now been expanded to analyze color segregation in juvenile scallops produced under controlled conditions employing self- and cross-fertilization. Calculations from the results were used for comparison with different numerical models based on Mendelian inheritance, and results were also obtained on the inheritance of a dorsoventral white line often observed on the left (upper) valve in this species. The results confirmed the hereditary basis for color variation in the shell of this scallop, suggesting a simple, dominant model of epistasis to explain the distribution of the different color variants observed (purple, brown, orange, yellow, and white). The presence of the white line may be controlled by a recessive allele with simple Mendelian traits on a locus distinct from those that control color variation.

  20. Phenotype and genotype of deaf patients with combined genomic and mitochondrial inheritance models.

    PubMed

    Huang, Shasha; Wang, Guojian; Jiang, Yi; Yuan, Yongyi; Han, Dongyi; Song, Yueshuai; Dai, Pu

    2013-11-01

    In most studies, sensorineural hearing loss is reported as a single-gene disease with autosomal dominant or autosomal recessive or with X-linked or maternal inheritance. It is uncommon that the hearing impairment is caused by a combined inheritance model including genomic and mitochondrial models. Here, we report six patients with sensorineural hearing loss caused by co-existing mutations in GJB2 or SLC26A4 and the mitochondrial gene. And there was no significant difference in hearing phenotypes between the six patients and the controls. The results indicate the complicated genetic etiology of, and may impact the diagnostic strategy for, hereditary hearing impairment. All patient siblings will carry mitochondrial DNA A1555G or C1494T mutations, and 25% of siblings may carry the same homozygous or compound heterozygote mutations in GJB2 or SLC26A4. Although this combined inheritance is not common in the Chinese deaf population (0.10%), our findings will have great impact in genetic counseling and risk prediction for deafness.

  1. The Great Recession in Portugal: impact on hospital care use.

    PubMed

    Perelman, Julian; Felix, Sónia; Santana, Rui

    2015-03-01

    The Great Recession started in Portugal in 2009, coupled with severe austerity. This study examines its impact on hospital care utilization, interpreted as caused by demand-side effects (related to variations in population income and health) and supply-side effects (related to hospitals' tighter budgets and reduced capacity). The database included all in-patient stays at all Portuguese NHS hospitals over the 2001-2012 period (n=17.7 millions). We analyzed changes in discharge rates, casemix index, and length of stay (LOS), using a before-after methodology. We additionally measured the association of health care indicators to unemployment. A 3.2% higher rate of discharges was observed after 2009. Urgent stays increased by 2.5%, while elective in-patient stays decreased by 1.4% after 2011. The LOS was 2.8% shorter after the crisis onset, essentially driven by the 4.5% decrease among non-elective stays. A one percentage point increase in unemployment rate was associated to a 0.4% increase in total volume, a 2.3% decrease in day cases, and a 0.1% decrease in LOS. The increase in total and urgent cases may reflect delayed out-patient care and health deterioration; the reduced volume of elective stays possibly signal a reduced capacity; finally, the shorter stays may indicate either efficiency-enhancing measures or reduced quality.

  2. Telomere length and heredity: Indications of paternal inheritance.

    PubMed

    Nordfjäll, Katarina; Larefalk, Asa; Lindgren, Petter; Holmberg, Dan; Roos, Göran

    2005-11-08

    Cellular telomere length is linked to replicative life span. Telomere repeats are lost in peripheral blood cells in vivo by age, and women show less telomere attrition than men. Previous reports have indicated that telomere length and chromosome-specific telomere-length patterns partly are inherited. The mode of heredity has not been clarified, but a link to the X chromosome was recently suggested. We analyzed peripheral mononuclear cells from 49 unrelated families for telomere length using a real-time PCR method. Short-term cultured Epstein-Barr virus-transformed lymphoblasts from the same individuals (n = 130) were analyzed for ability to maintain telomere length and possible gender-linked inheritance. A statistically significant association between telomere lengths comparing father-son (P = 0.011, n = 20) and father-daughter (P = 0.005, n = 22) pairs was found. However, no correlation was observed between mother-daughter (P = 0.463, n = 23) or mother-son (P = 0.577, n = 18). The father-offspring correlation was highly significant (P < 0.0001), in contrast to mother-offspring (P = 0.361). Epstein-Barr virus cultures demonstrated in most cases telomere preservation inversely related to initial mononuclear cell telomere length with short telomeres displaying the most pronounced elongation. Telomere length is inherited, and evidence for a father-to-offspring heritage of this trait was obtained, whereas in vitro telomere length maintenance was found to be dependent on the initial telomere length.

  3. Sex determination directs uniparental mitochondrial inheritance in Phycomyces.

    PubMed

    Shakya, Viplendra P S; Idnurm, Alexander

    2014-02-01

    Uniparental inheritance (UPI) of mitochondria is common among eukaryotes. The underlying molecular basis by which the sexes of the parents control this non-Mendelian pattern of inheritance is yet to be fully understood. Two major factors have complicated the understanding of the role of sex-specific genes in the UPI phenomenon: in many cases (i) fusion occurs between cells of unequal size or (ii) mating requires a large region of the genome or chromosome that includes genes unrelated to sex determination. The fungus Phycomyces blakesleeanus is a member of the Mucoromycotina and has a simple mating type locus encoding only one high-mobility group (HMG) domain protein, and mating occurs by fusion of isogamous cells, thus providing a model system without the limitations mentioned above. Analysis of more than 250 progeny from a series of genetic crosses between wild-type strains of Phycomyces revealed a correlation between the individual genes in the mating type locus and UPI of mitochondria. Inheritance is from the plus (+) sex type and is associated with degradation of the mtDNA from the minus (-) parent. These findings suggest that UPI can be directly controlled by genes that determine sex identity, independent of cell size or the complexity of the genetic composition of a sex chromosome.

  4. Economic recession and mental health: an overview.

    PubMed

    Cooper, Brian

    2011-01-01

    Effects of the current global economic downturn on population mental health will emerge in the years ahead. Judging from earlier experience of financial crises in various parts of the world, stresses associated with rising unemployment, poverty and social insecurity will lead to upward trends in many national suicide rates, as well as to less readily charted increase in the prevalence of psychiatric illness, alcohol-related disorders and illicit drug use. At the same time, mental health services are being cut back as part of government austerity programs. Budget cuts will thus affect psychiatric services adversely just when economic stressors are raising the levels of need and demand in affected populations. Proactive fiscal and social policies could, however, help to mitigate the health consequences of recession. Evidence- based preventive measures include active labor market and family support programs, regulation of alcohol prices and availability, community care for known high-risk groups, and debt relief projects. Economic mental health care could best be achieved, not by decimating services but by planning and deploying these to meet the needs of defined area populations.

  5. Calibration apparatus for recess mounted pressure transducers

    NASA Astrophysics Data System (ADS)

    Marcolini, Michael A.; Miller, William T., Jr.; Baals, Robert A.; Martin, Ruth M.

    1992-04-01

    Measurement of surface pressure fluctuations is important in aerodynamic studies and is conventionally accomplished via thin surface mounted transducers. These transducers contaminate the airflow, leading to the use of transducers located beneath the surface and communicating thereto via a pipette. This solution creates its own problem of transducer calibration due to the structure of the pipette. A calibration apparatus and method for calibrating a pressure transducer are provided. The pressure transducer is located within a test structure having a pipette leading from an outer structure surface to the pressure transducer. The calibration apparatus defines an acoustic cavity. A first end of the acoustic cavity is adapted to fluidly communicate with the pipette leading to the pressure transducer, wherein a channel is formed from the acoustic cavity to the transducer. An acoustic driver is provided for acoustically exciting fluid in the acoustic cavity to generate pressure waves which propagate to the pressure transducer. A pressure sensing microphone is provided for sensing the pressure fluctuations in the cavity near the cavity end, whereby this sensed pressure is compared with a simultaneously pressure sensed by the pressure transducer to permit calibration of the pressure transducer sensings. Novel aspects of the present invention include its use of a calibration apparatus to permit in-situ calibration of recess mounted pressure transducers.

  6. On the use of spring baseflow recession for a more accurate parameterization of aquifer transit time distribution functions

    NASA Astrophysics Data System (ADS)

    Farlin, J.; Maloszewski, P.

    2013-05-01

    Baseflow recession analysis and groundwater dating have up to now developed as two distinct branches of hydrogeology and have been used to solve entirely different problems. We show that by combining two classical models, namely the Boussinesq equation describing spring baseflow recession, and the exponential piston-flow model used in groundwater dating studies, the parameters describing the transit time distribution of an aquifer can be in some cases estimated to a far more accurate degree than with the latter alone. Under the assumption that the aquifer basis is sub-horizontal, the mean transit time of water in the saturated zone can be estimated from spring baseflow recession. This provides an independent estimate of groundwater transit time that can refine those obtained from tritium measurements. The approach is illustrated in a case study predicting atrazine concentration trend in a series of springs draining the fractured-rock aquifer known as the Luxembourg Sandstone. A transport model calibrated on tritium measurements alone predicted different times to trend reversal following the nationwide ban on atrazine in 2005 with different rates of decrease. For some of the springs, the actual time of trend reversal and the rate of change agreed extremely well with the model calibrated using both tritium measurements and the recession of spring discharge during the dry season. The agreement between predicted and observed values was however poorer for the springs displaying the most gentle recessions, possibly indicating a stronger influence of continuous groundwater recharge during the summer months.

  7. On the use of spring baseflow recession for a more accurate parameterization of aquifer transit time distribution functions

    NASA Astrophysics Data System (ADS)

    Farlin, J.; Maloszewski, P.

    2012-12-01

    Baseflow recession analysis and groundwater dating have up to now developed as two distinct branches of hydrogeology and were used to solve entirely different problems. We show that by combining two classical models, namely Boussinesq's Equation describing spring baseflow recession and the exponential piston-flow model used in groundwater dating studies, the parameters describing the transit time distribution of an aquifer can be in some cases estimated to a far more accurate degree than with the latter alone. Under the assumption that the aquifer basis is sub-horizontal, the mean residence time of water in the saturated zone can be estimated from spring baseflow recession. This provides an independent estimate of groundwater residence time that can refine those obtained from tritium measurements. This approach is demonstrated in a case study predicting atrazine concentration trend in a series of springs draining the fractured-rock aquifer known as the Luxembourg Sandstone. A transport model calibrated on tritium measurements alone predicted different times to trend reversal following the nationwide ban on atrazine in 2005 with different rates of decrease. For some of the springs, the best agreement between observed and predicted time of trend reversal was reached for the model calibrated using both tritium measurements and the recession of spring discharge during the dry season. The agreement between predicted and observed values was however poorer for the springs displaying the most gentle recessions, possibly indicating the stronger influence of continuous groundwater recharge during the dry period.

  8. Recessions, Job Loss, and Mortality Among Older US Adults

    PubMed Central

    Beckfield, Jason

    2014-01-01

    Objectives. We analyzed how recessions and job loss jointly shape mortality risks among older US adults. Methods. We used data for 50 states from the Health and Retirement Study and selected individuals who were employed at ages 45 to 66 years during 1992 to 2011. We assessed whether job loss affects mortality risks, whether recessions moderate the effect of job loss on mortality, and whether individuals who do and do not experience job loss are differentially affected by recessions. Results. Compared with individuals not experiencing job loss, mortality risks among individuals losing their job in a recession were strongly elevated (hazard ratio = 1.6; 95% confidence interval = 1.1, 2.3). Job loss during normal times or booms is not associated with mortality. For employed workers, we found a reduction in mortality risks if local labor market conditions were depressed, but this result was not consistent across different model specifications. Conclusions. Recessions increase mortality risks among older US adults who experience job loss. Health professionals and policymakers should target resources to this group during recessions. Future research should clarify which health conditions are affected by job loss during recessions and whether access to health care following job loss moderates this relation. PMID:25211731

  9. A general geomorphological recession flow model for river basins

    NASA Astrophysics Data System (ADS)

    Biswal, Basudev; Nagesh Kumar, D.

    2013-08-01

    Recession flows in a basin are controlled by the temporal evolution of its active drainage network (ADN). The geomorphological recession flow model (GRFM) assumes that both the rate of flow generation per unit ADN length (q) and the speed at which ADN heads move downstream (c) remain constant during a recession event. Thereby, it connects the power law exponent of -dQ/dt versus Q (discharge at the outlet at time t) curve, α, with the structure of the drainage network, a fixed entity. In this study, we first reformulate the GRFM for Horton-Strahler networks and show that the geomorphic α (αg) is equal to D/>(D-1>), where D is the fractal dimension of the drainage network. We then propose a more general recession flow model by expressing both q and c as functions of Horton-Strahler stream order. We show that it is possible to have α =α g for a recession event even when q and c do not remain constant. The modified GRFM suggests that α is controlled by the spatial distribution of subsurface storage within the basin. By analyzing streamflow data from 39 U.S. Geological Survey basins, we show that α is having a power law relationship with recession curve peak, which indicates that the spatial distribution of subsurface storage varies across recession events.

  10. New method for calculating a mathematical expression for streamflow recession

    USGS Publications Warehouse

    Rutledge, Albert T.

    1991-01-01

    An empirical method has been devised to calculate the master recession curve, which is a mathematical expression for streamflow recession during times of negligible direct runoff. The method is based on the assumption that the storage-delay factor, which is the time per log cycle of streamflow recession, varies linearly with the logarithm of streamflow. The resulting master recession curve can be nonlinear. The method can be executed by a computer program that reads a data file of daily mean streamflow, then allows the user to select several near-linear segments of streamflow recession. The storage-delay factor for each segment is one of the coefficients of the equation that results from linear least-squares regression. Using results for each recession segment, a mathematical expression of the storage-delay factor as a function of the log of streamflow is determined by linear least-squares regression. The master recession curve, which is a second-order polynomial expression for time as a function of log of streamflow, is then derived using the coefficients of this function.

  11. A differential diagnosis of inherited endocrine tumors and their tumor counterparts

    PubMed Central

    Toledo, Sergio P. A.; Lourenço, Delmar M.; Toledo, Rodrigo A.

    2013-01-01

    Inherited endocrine tumors have been increasingly recognized in clinical practice, although some difficulties still exist in differentiating these conditions from their sporadic endocrine tumor counterparts. Here, we list the 12 main topics that could add helpful information and clues for performing an early differential diagnosis to distinguish between these conditions. The early diagnosis of patients with inherited endocrine tumors may be performed either clinically or by mutation analysis in at-risk individuals. Early detection usually has a large impact in tumor management, allowing preventive clinical or surgical therapy in most cases. Advice for the clinical and surgical management of inherited endocrine tumors is also discussed. In addition, recent clinical and genetic advances for 17 different forms of inherited endocrine tumors are briefly reviewed. PMID:23917672

  12. Causes and consequences of inherited cone disorders.

    PubMed

    Roosing, Susanne; Thiadens, Alberta A H J; Hoyng, Carel B; Klaver, Caroline C W; den Hollander, Anneke I; Cremers, Frans P M

    2014-09-01

    Hereditary cone disorders (CDs) are characterized by defects of the cone photoreceptors or retinal pigment epithelium underlying the macula, and include achromatopsia (ACHM), cone dystrophy (COD), cone-rod dystrophy (CRD), color vision impairment, Stargardt disease (STGD) and other maculopathies. Forty-two genes have been implicated in non-syndromic inherited CDs. Mutations in the 5 genes implicated in ACHM explain ∼93% of the cases. On the contrary, only 21% of CRDs (17 genes) and 25% of CODs (8 genes) have been elucidated. The fact that the large majority of COD and CRD-associated genes are yet to be discovered hints towards the existence of unknown cone-specific or cone-sensitive processes. The ACHM-associated genes encode proteins that fulfill crucial roles in the cone phototransduction cascade, which is the most frequently compromised (10 genes) process in CDs. Another 7 CD-associated proteins are required for transport processes towards or through the connecting cilium. The remaining CD-associated proteins are involved in cell membrane morphogenesis and maintenance, synaptic transduction, and the retinoid cycle. Further novel genes are likely to be identified in the near future by combining large-scale DNA sequencing and transcriptomics technologies. For 31 of 42 CD-associated genes, mammalian models are available, 14 of which have successfully been used for gene augmentation studies. However, gene augmentation for CDs should ideally be developed in large mammalian models with cone-rich areas, which are currently available for only 11 CD genes. Future research will aim to elucidate the remaining causative genes, identify the molecular mechanisms of CD, and develop novel therapies aimed at preventing vision loss in individuals with CD in the future.

  13. The incidence of inherited porphyrias in Europe.

    PubMed

    Elder, George; Harper, Pauline; Badminton, Michael; Sandberg, Sverre; Deybach, Jean-Charles

    2013-09-01

    Retrospective estimates of the prevalence of porphyrias have been reported but there has been no large scale prospective study of their incidence. The European Porphyria Network collected information prospectively over a 3 year period about the number of newly diagnosed symptomatic patients with an inherited porphyria (335 patients from 11 countries). Prevalence was calculated from the incidence and mean disease duration. The incidence of hepato-cellular carcinoma (HCC) in acute hepatic porphyria and the prevalence of patients with recurrent acute attacks of porphyria were also investigated. The incidence of symptomatic acute intermittent porphyria (AIP) was similar in all countries (0.13 per million per year; 95 % CI: 0.10 - 0.14) except Sweden (0.51; 95 % CI: 0.28-0.86). The incidence ratio for symptomatic AIP: variegate porphyria: hereditary coproporphyria was 1.00:0.62: 0.15. The prevalence of AIP (5.4 per million; 95 % CI: 4.5-6.3) was about half that previously reported. The prevalence of erythropoietic protoporphyria (EPP) was less uniform between countries and, in some countries, exceeded previous estimates. Fourteen new cases of HCC (11 from Sweden) were reported in patients with acute porphyria. Sixty seven patients (3 VP; 64 AIP: 53 females, 11 males) with recurrent attacks of acute porphyria were identified. The estimated percentage of patients with AIP that will develop recurrent acute attacks was 3-5 %. In conclusion, the prevalence of symptomatic acute porphyria may be decreasing, possibly due to improved management, whereas the prevalence of EPP may be increasing due to improved diagnosis and its greater recognition as a cause of photosensitivity.

  14. Surgical management of gingival recession: A clinical update

    PubMed Central

    Alghamdi, Hamdan; Babay, Nadir; Sukumaran, Anil

    2009-01-01

    Gingival recession is defined as the apical migration of the junctional epithelium with exposure of root surfaces. It is a common condition seen in both dentally aware populations and those with limited access to dental care. The etiology of the condition is multifactorial but is commonly associated with underlying alveolar morphology, tooth brushing, mechanical trauma and periodontal disease. Given the high rate of gingival recession defects among the general population, it is imperative that dental practitioners have an understanding of the etiology, complications and the management of the condition. The following review describes the surgical techniques to treat gingival recession. PMID:23960465

  15. The nonuniform recession of the south polar cap of Mars

    NASA Technical Reports Server (NTRS)

    Veverka, J.; Goguen, J.

    1973-01-01

    The nature of the irregular springtime recession of the Martian polar caps is investigated, with particular reference to the southern polar cap. Our current knowledge about the composition of the caps is outlined, and the historical record of their springtime recession is reviewed. An attempt is made to correlate the irregularities of the recession pattern of the southern polar cap with the features of the terrain revealed by Mariner 9 photography at a time when the southern cap was at its minimum extent. The results are interpreted in terms of the physical and meteorological processes active in the polar regions.

  16. Increasing physical activity of children during school recess.

    PubMed

    Hayes, Lynda B; Van Camp, Carole M

    2015-09-01

    Physical activity is crucial for children's health. Fitbit accelerometers were used to measure steps of 6 elementary students during recess. The intervention included reinforcement, self-monitoring, goal setting, and feedback. Steps taken during the intervention phase (M = 1,956 steps) were 47% higher than in baseline (M = 1,326 steps), and the percentage of recess spent in moderate-to-vigorous physical activity was higher during intervention (M = 25%) than in baseline (M = 4%). These methods successfully increased steps during recess and could be used to increase steps in other settings.

  17. Inherited cardiomyopathies mimicking arrhythmogenic right ventricular cardiomyopathy.

    PubMed

    Roberts, Jason D; Veinot, John P; Rutberg, Julie; Gollob, Michael H

    2010-01-01

    Arrhythmogenic right ventricular cardiomyopathy (ARVC) represents an inherited cardiomyopathy that manifests clinically with malignant ventricular arrhythmias, sudden cardiac death, and less commonly heart failure. The condition is characterized by replacement of the myocardium, primarily of the right ventricle, with fibrofatty tissue. Extensive fibrofatty replacement of the myocardium has been previously thought to be pathognomonic of ARVC; however, this report details two other forms of inherited cardiomyopathy, namely hypertrophic cardiomyopathy (HCM) and the PRKAG2 cardiac syndrome, that were found to have significant fibrofatty myocardial replacement at pathologic examination. This report represents the first documentation of inherited cardiomyopathies mimicking ARVC and highlights the concept that other cardiac conditions can be associated with fibrofatty replacement of the myocardium.

  18. Transgenerational epigenetic inheritance: an open discussion.

    PubMed

    Nagy, Corina; Turecki, Gustavo

    2015-08-01

    Much controversy surrounds the idea of transgenerational epigenetics. Recent papers argue that epigenetic marks acquired through experience are passed to offspring, but as in much of the field of epigenetics, there is lack of precision in the definitions and perhaps too much eagerness to translate animal research to humans. Here, we review operational definitions of transgenerational inheritance and the processes of epigenetic programing during early development. Subsequently, based on this background, we critically examine some recent findings of studies investigating transgenerational inheritance. Finally, we discuss possible mechanisms that may explain transgenerational inheritance, including transmission of an epigenetic blueprint, which may predispose offspring to specific epigenetic patterning. Taken together, we conclude that presently, the evidence suggesting that acquired epigenetic marks are passed to the subsequent generation remains limited.

  19. Environmental stress and epigenetic transgenerational inheritance.

    PubMed

    Skinner, Michael K

    2014-09-05

    Previous studies have shown a wide variety of environmental toxicants and abnormal nutrition can promote the epigenetic transgenerational inheritance of disease. More recently a number of studies have indicated environmental stress can also promote epigenetic alterations that are transmitted to subsequent generations to induce pathologies. A recent study by Yao and colleagues demonstrated gestational exposure to restraint stress and forced swimming promoted preterm birth risk and adverse newborn outcomes generationally. This ancestral stress promoted the epigenetic transgenerational inheritance of abnormalities in the great-grand offspring of the exposed gestating female. Several studies now support the role of environmental stress in promoting the epigenetic transgenerational inheritance of disease. Observations suggest ancestral environmental stress may be a component of disease etiology in the current population.

  20. Quantitative Fundus Autofluorescence in Recessive Stargardt Disease

    PubMed Central

    Burke, Tomas R.; Duncker, Tobias; Woods, Russell L.; Greenberg, Jonathan P.; Zernant, Jana; Tsang, Stephen H.; Smith, R. Theodore; Allikmets, Rando; Sparrow, Janet R.; Delori, François C.

    2014-01-01

    Purpose. To quantify fundus autofluorescence (qAF) in patients with recessive Stargardt disease (STGD1). Methods. A total of 42 STGD1 patients (ages: 7–52 years) with at least one confirmed disease-associated ABCA4 mutation were studied. Fundus AF images (488-nm excitation) were acquired with a confocal scanning laser ophthalmoscope equipped with an internal fluorescent reference to account for variable laser power and detector sensitivity. The gray levels (GLs) of each image were calibrated to the reference, zero GL, magnification, and normative optical media density to yield qAF. Texture factor (TF) was calculated to characterize inhomogeneities in the AF image and patients were assigned to the phenotypes of Fishman I through III. Results. Quantified fundus autofluorescence in 36 of 42 patients and TF in 27 of 42 patients were above normal limits for age. Young patients exhibited the relatively highest qAF, with levels up to 8-fold higher than healthy eyes. Quantified fundus autofluorescence and TF were higher in Fishman II and III than Fishman I, who had higher qAF and TF than healthy eyes. Patients carrying the G1916E mutation had lower qAF and TF than most other patients, even in the presence of a second allele associated with severe disease. Conclusions. Quantified fundus autofluorescence is an indirect approach to measuring RPE lipofuscin in vivo. We report that ABCA4 mutations cause significantly elevated qAF, consistent with previous reports indicating that increased RPE lipofuscin is a hallmark of STGD1. Even when qualitative differences in fundus AF images are not evident, qAF can elucidate phenotypic variation. Quantified fundus autofluorescence will serve to establish genotype-phenotype correlations and as an outcome measure in clinical trials. PMID:24677105

  1. Private inherited microdeletion/microduplications: implications in clinical practice.

    PubMed

    Mencarelli, Maria Antonietta; Katzaki, Eleni; Papa, Filomena Tiziana; Sampieri, Katia; Caselli, Rossella; Uliana, Vera; Pollazzon, Marzia; Canitano, Roberto; Mostardini, Rosa; Grosso, Salvatore; Longo, Ilaria; Ariani, Francesca; Meloni, Ilaria; Hayek, Josef; Balestri, Paolo; Mari, Francesca; Renieri, Alessandra

    2008-01-01

    The introduction of array-CGH analysis is allowing the identification of novel genomic disorders. However, this new high-resolution technique is also opening novel diagnostic challenges when inherited private CNVs of unclear clinical significance are found. Oligo array-CGH analysis of 84 patients with mild to severe mental retardation associated with multiple congenital anomalies revealed 10 private CNVs inherited from a healthy parent. Three were deletions (7q31, 14q21.1, Xq25) and seven duplications (12p11.22, 12q21.31, 13q31.1, 17q12, Xp22.31, Xq28) ranging between 0.1 and 3.8Mb. Six rearrangements were not polymorphic. Four overlapped polymorphic regions to the extent of 10-61%. In one case the size was different between the proband and the healthy relative. Three small rearrangements were gene deserts. The remaining seven had a mean gene content of five (ranging from 1 to 18). None of the rearranged genes is known to be imprinted. Three disease-genes were found in three different cases: KAL1 in dupXp22.31, STS in another dupXp22.31 and TCF2 in dup17q12. The patient carrying the last duplication presents sex reversal, Peters' anomaly and renal cysts and the duplication is located 4Mb away from the HSD17B1 gene, coding a key enzyme of testosterone biosynthesis. Considering the overlap with polymorphic regions, size-identity within the family, gene content, kind of rearrangement and size of rearrangement we suggest that at least in five cases the relationship to the phenotype has not to be excluded. We recommend to maintain caution when asserting that chromosomal abnormalities inherited from a healthy parent are benign. A more complex mechanism may in fact be involved, such as a concurrent variation in the other allele or in another chromosome that influences the phenotype.

  2. Mitochondrial dynamics and inherited peripheral nerve diseases.

    PubMed

    Pareyson, Davide; Saveri, Paola; Sagnelli, Anna; Piscosquito, Giuseppe

    2015-06-02

    Peripheral nerves have peculiar energetic requirements because of considerable length of axons and therefore correct mitochondria functioning and distribution along nerves is fundamental. Mitochondrial dynamics refers to the continuous change in size, shape, and position of mitochondria within cells. Abnormalities of mitochondrial dynamics produced by mutations in proteins involved in mitochondrial fusion (mitofusin-2, MFN2), fission (ganglioside-induced differentiation-associated protein-1, GDAP1), and mitochondrial axonal transport usually present with a Charcot-Marie-Tooth disease (CMT) phenotype. MFN2 mutations cause CMT type 2A by altering mitochondrial fusion and trafficking along the axonal microtubule system. CMT2A is an axonal autosomal dominant CMT type which in most cases is characterized by early onset and rather severe course. GDAP1 mutations also alter fission, fusion and transport of mitochondria and are associated either with recessive demyelinating (CMT4A) and axonal CMT (AR-CMT2K) and, less commonly, with dominant, milder, axonal CMT (CMT2K). OPA1 (Optic Atrophy-1) is involved in fusion of mitochondrial inner membrane, and its heterozygous mutations lead to early-onset and progressive dominant optic atrophy which may be complicated by other neurological symptoms including peripheral neuropathy. Mutations in several proteins fundamental for the axonal transport or forming the axonal cytoskeleton result in peripheral neuropathy, i.e., CMT, distal hereditary motor neuropathy (dHMN) or hereditary sensory and autonomic neuropathy (HSAN), as well as in hereditary spastic paraplegia. Indeed, mitochondrial transport involves directly or indirectly components of the kinesin superfamily (KIF5A, KIF1A, KIF1B), responsible of anterograde transport, and of the dynein complex and related proteins (DYNC1H1, dynactin, dynamin-2), implicated in retrograde flow. Microtubules, neurofilaments, and chaperones such as heat shock proteins (HSPs) also have a fundamental

  3. Whole exome sequencing identifies three recessive FIG4 mutations in an apparently dominant pedigree with Charcot-Marie-Tooth disease.

    PubMed

    Menezes, Manoj P; Waddell, Leigh; Lenk, Guy M; Kaur, Simranpreet; MacArthur, Daniel G; Meisler, Miriam H; Clarke, Nigel F

    2014-08-01

    Charcot-Marie-Tooth disease (CMT) is genetically heterogeneous and classification based on motor nerve conduction velocity and inheritance is used to direct genetic testing. With the less common genetic forms of CMT, identifying the causative genetic mutation by Sanger sequencing of individual genes can be time-consuming and costly. Next-generation sequencing technologies show promise for clinical testing in diseases where a similar phenotype is caused by different genes. We report the unusual occurrence of CMT4J, caused by mutations in FIG4, in a apparently dominant pedigree. The affected proband and her mother exhibit different disease severities associated with different combinations of compound heterozygous FIG4 mutations, identified by whole exome sequencing. The proband was also shown to carry a de novo nonsense mutation in the dystrophin gene, which may contribute to her more severe phenotype. This study is a cautionary reminder that in families with two generations affected, explanations other than dominant inheritance are possible, such as recessive inheritance due to three mutations segregating in the family. It also emphasises the advantages of next-generation sequencing approaches that screen multiple CMT genes at once for patients in whom the common genes have been excluded.

  4. Transgenerational epigenetic inheritance: how important is it?

    PubMed

    Grossniklaus, Ueli; Kelly, William G; Kelly, Bill; Ferguson-Smith, Anne C; Pembrey, Marcus; Lindquist, Susan

    2013-03-01

    Much attention has been given to the idea of transgenerational epigenetic inheritance, but fundamental questions remain regarding how much takes place and the impact that this might have on organisms. We asked five leading researchers in this area--working on a range of model organisms and in human disease--for their views on these topics. Their responses highlight the mixture of excitement and caution that surrounds transgenerational epigenetic inheritance and the wide gulf between species in terms of our knowledge of the mechanisms that may be involved.

  5. New patterns of inheritance in mitochondrial disease.

    PubMed

    Schwartz, Marianne; Vissing, John

    2003-10-17

    With the identification of a patient with mutated mitochondrial DNA (mtDNA) of paternal origin, it has been unequivocally proven that not only does paternal mtDNA survive in the zygote, but it can also contribute substantially to the mtDNA pool of adult, human skeletal muscle. The questions are: how often does paternal mtDNA inheritance occur and what mechanisms are involved? In this paper, we will review current knowledge on the fate of sperm mitochondria after fertilization and discuss the impact paternal inheritance may have on our understanding of mitochondrial biology.

  6. Miniature paint-spray gun for recessed areas

    NASA Technical Reports Server (NTRS)

    Vanasse, M. A.

    1968-01-01

    Miniature spray gun regulates paints and other liquids to spray at close range, facilitating spraying of remote or recessed areas. Individual valves for regulating air pressure and paint maximizes atomization for low pressure spraying.

  7. HYDRORECESSION: A Matlab toolbox for streamflow recession analysis

    NASA Astrophysics Data System (ADS)

    Arciniega-Esparza, Saúl; Breña-Naranjo, José Agustín; Pedrozo-Acuña, Adrián; Appendini, Christian Mario

    2017-01-01

    Streamflow recession analysis from observed hydrographs allows to extract information about the storage-discharge relationship of a catchment and some of their groundwater hydraulic properties. The HYDRORECESSION toolbox, presented in this paper, is a graphical user interface for Matlab and it was developed to analyse streamflow recession curves with the support of different tools. The software extracts hydrograph recessions segments with three different methods (Vogel, Brutsaert and Aksoy) that are later analysed with four of the most common models to simulate recession curves (Maillet, Boussinesq, Coutagne and Wittenberg) and it includes four parameter-fitting techniques (linear regression, lower envelope, data binning and mean squared error). HYDRORECESSION offers tools to parameterize linear and nonlinear storage-outflow relationships and it is useful for regionalization purposes, catchment classification, baseflow separation, hydrological modeling and low flows prediction. HYDRORECESSION is freely available for non-commercial and academic purposes and is available at Matlab File Exchange (http://www.mathworks.com/matlabcentral/fileexchange/51332-hydroecession).

  8. Chemical-mechanical polishing of recessed microelectromechanical devices

    DOEpatents

    Barron, Carole C.; Hetherington, Dale L.; Montague, Stephen

    1999-01-01

    A method is disclosed for micromachining recessed layers (e.g. sacrificial layers) of a microelectromechanical system (MEMS) device formed in a cavity etched into a semiconductor substrate. The method uses chemical-mechanical polishing (CMP) with a resilient polishing pad to locally planarize one or more of the recessed layers within the substrate cavity. Such local planarization using the method of the present invention is advantageous for improving the patterning of subsequently deposited layers, for eliminating mechanical interferences between functional elements (e.g. linkages) of the MEMS device, and for eliminating the formation of stringers. After the local planarization of one or more of the recessed layers, another CMP step can be provided for globally planarizing the semiconductor substrate to form a recessed MEMS device which can be integrated with electronic circuitry (e.g. CMOS, BiCMOS or bipolar circuitry) formed on the surface of the substrate.

  9. Chemical-mechanical polishing of recessed microelectromechanical devices

    DOEpatents

    Barron, C.C.; Hetherington, D.L.; Montague, S.

    1999-07-06

    A method is disclosed for micromachining recessed layers (e.g. sacrificial layers) of a microelectromechanical system (MEMS) device formed in a cavity etched into a semiconductor substrate. The method uses chemical-mechanical polishing (CMP) with a resilient polishing pad to locally planarize one or more of the recessed layers within the substrate cavity. Such local planarization using the method of the present invention is advantageous for improving the patterning of subsequently deposited layers, for eliminating mechanical interferences between functional elements (e.g. linkages) of the MEMS device, and for eliminating the formation of stringers. After the local planarization of one or more of the recessed layers, another CMP step can be provided for globally planarizing the semiconductor substrate to form a recessed MEMS device which can be integrated with electronic circuitry (e.g., CMOS, BiCMOS or bipolar circuitry) formed on the surface of the substrate. 23 figs.

  10. Evidence of the phenotypic expression of a lethal recessive allele under inbreeding in a wild population of conservation concern.

    PubMed

    Trask, Amanda E; Bignal, Eric M; McCracken, Davy I; Monaghan, Pat; Piertney, Stuart B; Reid, Jane M

    2016-07-01

    Deleterious recessive alleles that are masked in outbred populations are predicted to be expressed in small, inbred populations, reducing both individual fitness and population viability. However, there are few definitive examples of phenotypic expression of lethal recessive alleles under inbreeding conditions in wild populations. Studies that demonstrate the action of such alleles, and infer their distribution and dynamics, are required to understand their potential impact on population viability and inform management responses. The Scottish population of red-billed choughs (Pyrrhocorax pyrrhocorax), which currently totals <60 breeding pairs and is of major conservation concern, has recently been affected by lethal blindness in nestlings. We used family data to show that the pattern of occurrence of blindness within and across affected families that produced blind nestlings was exactly 0·25, matching that expected given a single-locus autosomal lethal recessive allele. Furthermore, the observed distribution of blind nestlings within affected families did not differ from that expected given Mendelian inheritance of such an allele. Relatedness estimates showed that individuals from affected families were not more closely related to each other than they were to individuals from unaffected families that did not produce blind nestlings. Blind individuals tended to be less heterozygous than non-blind individuals, as expected if blindness was caused by the expression of a recessive allele under inbreeding. However, there was no difference in the variance in heterozygosity estimates, suggesting that some blind individuals were relatively outbred. These results suggest carriers of the blindness allele may be widely distributed across contemporary families rather than restricted to a single family lineage, implying that the allele has persisted across multiple generations. Blindness occurred at low frequency (affecting 1·6% of observed nestlings since 1981). However

  11. 'Immobile' (im), a recessive lethal mutation of Xenopus laevis tadpoles.

    PubMed

    Droin, A; Beauchemin, M L

    1975-10-01

    'Immobile' (im) is a recessive lethal mutation discovered in the F3 of a Xenopus (Xenopus laevis laevis) originating from a mesodermal nucleus of a neurula transplanted into an enucleated egg. The im embryos do not contract after mechanical stimulation nor do they present any spontaneous contraction from the neurula stage onwards. Development proceeds normally during the first days after which deformation of the lower jaw and tail are observed. The im tadpoles die when normal controls are at the feeding stage. Nevous and muscular tissues are histologically normal in the mutant tadpoles; at advanced stages, however, an irregularity in the path of the myofibrils is observed which is especially conspicuous in the electron microscope. Cholinesterases and ATPase are present in the mutant muscles. Parabiosis and chimerae experiments have shown that parabionts and grafts behave according to their own genotype. Cultures of presumptive axial systems with or without ectoderm lead to the conclusion that, first of all, the abnormality is situated in the mesodermal cells and secondly that the first muscular contractions in normal Xenopus laevis are of myogenic origin. The banding pattern of the myofibrils is normal as was shown by obtaining contractions of glycerol extracted in myoblasts with ATP. It seems therefore that in this mutation, the abnormality is situated in the membraneous system of the muscular cell, sarcoplasmic reticulum and/or tubular system as is probably the case in the mdg mutation of the mouse.

  12. The recession of gastric cancer and its possible causes.

    PubMed

    Seely, S

    1978-01-01

    The paper re-examines the hypothesis that excessively hot drinks constitute an important risk factor in the causation of gastric cancer. The recession of gastric cancer mortality rates in the United States in recent decades is attributed to dietary changes tending to supplant the traditional hot beverages. One such change was the appearance of domestic refrigerators, promoting iced drinks, another the popularisation of soft drinks. The example of Okinawa is quoted where in 1972, after 27 years of American administration, gastric cancer mortality rate was 11.3 per 100,000, in contrast to Japan's 46.7, presumably due to the introduction of American dietary habits. While in most Western European countries gastric cancer risk decreased in the last decades, there was little change in Eastern Europe, and rates were rising in some countries, like Portugal, Mexico and Hong-Kong. This is attributed to the increasing pollution of water, promoting its boiling and flovouring. In some countries water is disinfected by chlorination in which case boiling and flavouring may be used to mask the unpleasant smell and taste of disinfectant.

  13. Has the great recession and its aftermath reduced traffic fatalities?

    PubMed

    Noland, Robert B; Zhou, Yuhan

    2017-01-01

    An analysis of state-level data from 1984 to 2014 provides evidence on the relationship between economic recessions and US traffic fatalities. While there are large reductions associated with decreases in household median income, other policy variables tend to have additional and in some cases, larger effects. An increase in the inequality of the income distribution, measured by the Gini index, has reduced traffic fatalities. Graduated licensing policies, cell phone laws, and motorcycle helmet requirements are all associated with reductions in fatalities. Other factors include a proxy for medical technology, and access to emergency medical services (based on the percent of vehicle miles traveled in rural areas); reductions in the latter accounted for a substantial reduction in fatalities and is likely another indicator of reduced economic activity. Changes in the road network, mainly increases in the percent of collector roads has increased fatalities. Population growth is associated with increased traffic fatalities and changes in age cohorts has a small negative effect. Overall, results suggest that there has been a beneficial impact on traffic fatalities from reduced economic activity, but various policies adopted by the states have also reduced traffic fatalities.

  14. Estimating parental relationship in linkage analysis of recessive traits

    SciTech Connect

    Merette, C.; Ott, J.

    1996-05-17

    In linkage analysis of recessive traits, parental relationship is important. For the case that it is unknown, the question is investigated as to whether estimating parental relationship and using the estimated relationship in linkage analysis is beneficial. Results show that estimating parental relationship can reliably be carried out on the basis of 50-100 genetic marker loci (analysis based on theory by Thompson). Misspecification of parental relationship leads to a loss of linkage informativeness, but not to false-positive evidence for linkage. An asymptotic bias in the recombination fraction estimate occurs when parents are unrelated and falsely taken to be related, but no such bias is seen when related parents are taken to be unrelated. Results from this investigation suggest that an estimated parental relationship may be used in linkage analysis as if it were the correct relationship, when evidence for the estimated relationship is supported by a likelihood ratio of at least 10:1 against the parents being unrelated. 9 refs., 2 figs., 5 tabs.

  15. Children's Physical Activity during Recess and Outside of School

    ERIC Educational Resources Information Center

    Beighle, Aaron; Morgan, Charles F.; Le Masurier, Guy; Pangrazi, Robert P.

    2006-01-01

    The purpose of this study was to examine children's physical activity during recess and outside of school. Third-, fourth-, and fifth-grade students (N = 270; 121 boys, age = 9.5 plus or minus 0.9 years; 150 girls, age = 9.6 plus or minus 0.9 years) wore sealed pedometers during a 15-minute recess period and outside of school for 4 consecutive…

  16. Gas insulated transmission line with insulators having field controlling recesses

    DOEpatents

    Cookson, Alan H.; Pederson, Bjorn O.

    1984-01-01

    A gas insulated transmission line having a novel insulator for supporting an inner conductor concentrically within an outer sheath. The insulator has a recess contiguous with the periphery of one of the outer and inner conductors. The recess is disposed to a depth equal to an optimum gap for the dielectric insulating fluid used for the high voltage insulation or alternately disposed to a large depth so as to reduce the field at the critical conductor/insulator interface.

  17. Mutations in the delta-sarcoglycan gene are a rare cause of autosomal recessive limb-girdle muscular dystrophy (LGMD2).

    PubMed

    Duggan, D J; Manchester, D; Stears, K P; Mathews, D J; Hart, C; Hoffman, E P

    1997-05-01

    The dystrophin-based membrane cytoskeleton of muscle fibers has emerged as a critical multi-protein complex which seems to impart structural integrity on the muscle fiber plasma membrane. Deficiency of dystrophin causes the most common types of muscular dystrophy, Duchenne and Becker muscular dystrophies. Muscular dystrophy patients showing normal dystrophin protein and gene analysis are generally isolated cases with a presumed autosomal recessive inheritance pattern (limb-girdle muscular dystrophy). Recently, linkage and candidate gene analyses have shown that some cases of limb-girdle muscular dystrophy can be caused by deficiency of other components of the dystrophin membrane cytoskeleton. The most recently identified component, delta-sarcoglycan, has been found to show mutations in a series of Brazilian muscular dystrophy patients. All patients were homozygous for a protein-truncating carboxy-terminal mutation, and showed a deficiency of the four sarcoglycan proteins. To determine if delta-sarcoglycan deficiency occurred in other world populations, to identify the range of mutations and clinical phenotypes, and to test for the biochemical consequences of delta-sarcoglycan gene mutations, we studied Duchenne-like and limb-girdle muscular dystrophy patients who we had previously shown not to exhibit gene mutations of dystrophin, alpha-, beta-, or gamma-sarcoglycan for delta-sarcoglycan mutations (n = 54). We identified two American patients with novel nonsense mutations of delta-sarcoglycan (W30X, R165X). One was apparently homozygous, and we show likely consanguinity through homozygosity for 13 microsatellite loci covering a 38 cM region of chromosome 5. The second was heterozygous. Both were girls who showed clinical symptoms consistent with Duchenne muscular dystrophy in males. Our data shows that delta-sarcoglycan deficiency occurs in other world populations, and that most or all patients show a deficiency of the entire sarcoglycan complex, adding support to

  18. Xeroderma pigmentosum: a case report and review of the literature.

    PubMed

    Feller, L; Wood, N H; Motswaledi, M H; Khammissa, R A G; Meyer, M; Lemmer, J

    2010-06-01

    Inherited molecular defects in nucleotide excision repair genes cause the autosomal recessive condition xeroderma pigmentosum. Xeroderma pigmentosum is characterized by photo-hypersensitivity of sun-exposed tissues, and by a several thousand-fold increase in the risk of developing malignant neoplasms of the skin and of the eyes. Mutations in xeroderma pigmentosum genes that regulate nucleotide excision repair, not only predispose persons with xeroderma pigmentosum to multiple malignancies, but also promote premature cutaneous and ocular ageing, and in some cases promote progressive neurodegenerative changes. This paper describes a case of xeroderma pigmentosum with advanced cutaneous squamous cell carcinoma, actinic cheilitis and ocular lesions in a 19-year-old black woman. The extensive ultraviolet radiation-induced skin and eye damage are evidence of neglect of sun-protection and lack of appropriate medical care from childhood.

  19. Doubly uniparental inheritance: two mitochondrial genomes, one precious model for organelle DNA inheritance and evolution.

    PubMed

    Passamonti, Marco; Ghiselli, Fabrizio

    2009-02-01

    Eukaryotes have exploited several mechanisms for organelle uniparental inheritance, so this feature arose and evolved independently many times in their history. Metazoans' mitochondria commonly experience strict maternal inheritance; that is, they are only transmitted by females. However, the most noteworthy exception comes from some bivalve mollusks, in which two mitochondrial lineages (together with their genomes) are inherited: one through females (F) and the other through males (M). M and F genomes show up to 30% sequence divergence. This inheritance mechanism is known as doubly uniparental inheritance (DUI), because both sexes inherit uniparentally their mitochondria. Here, we review what we know about this unusual system, and we propose a model for evolution of DUI that might account for its origin as sex determination mechanism. Moreover, we propose DUI as a choice model to address many aspects that should be of interest to a wide range of biological subfields, such as mitochondrial inheritance, mtDNA evolution and recombination, genomic conflicts, evolution of sex, and developmental biology. Actually, as research proceeds, mitochondria appear to have acquired a central role in many fundamental processes of life, which are not only in their metabolic activity as cellular power plants, such as cell signaling, fertilization, development, differentiation, ageing, apoptosis, and sex determination. A function of mitochondria in the origin and maintenance of sex has been also proposed.

  20. Vestibular Extension along with Frenectomy in Management of Localized Gingival Recession in Pediatric Patient: A New Innovative Surgical Approach.

    PubMed

    Jingarwar, Mahesh; Pathak, Anuradha; Bajwa, Navroop Kaur; Kalaskar, Ritesh

    2015-01-01

    This paper reports case of pediatric localized gingival recession (LGR) in mandibular anterior region which was treated by using new innovative surgical approach, i.e. combination of frenectomy and vestibular extension. These interceptive surgeries not only gained sufficient width of attached gingival but also lower the attachment of labial frenum. How to cite this article: Jingarwar M, Pathak A, Bajwa NK, Kalaskar R. Vestibular Extension along with Frenectomy in Management of Localized Gingival Recession in Pediatric Patient: A New Innovative Surgical Approach. Int J Clin Pediatr Dent 2015;8(3):224-226.

  1. Vestibular Extension along with Frenectomy in Management of Localized Gingival Recession in Pediatric Patient: A New Innovative Surgical Approach

    PubMed Central

    Pathak, Anuradha; Bajwa, Navroop Kaur; Kalaskar, Ritesh

    2015-01-01

    ABSTRACT This paper reports case of pediatric localized gingival recession (LGR) in mandibular anterior region which was treated by using new innovative surgical approach, i.e. combination of frenectomy and vestibular extension. These interceptive surgeries not only gained sufficient width of attached gingival but also lower the attachment of labial frenum. How to cite this article: Jingarwar M, Pathak A, Bajwa NK, Kalaskar R. Vestibular Extension along with Frenectomy in Management of Localized Gingival Recession in Pediatric Patient: A New Innovative Surgical Approach. Int J Clin Pediatr Dent 2015;8(3):224-226. PMID:26604542

  2. The Effects of the Great Recession on Educational Attainment: Evidence from a Large Urban High School District

    ERIC Educational Resources Information Center

    Mordechay, Kfir

    2017-01-01

    Economic crises are a recurrent phenomenon in American society, yet there is little knowledge of the impacts on educational opportunity. Using data from a large high school district as a case study, this research explores the impact of the Great Recession (2007-2009) on high school senior graduation rates in an area at the epicenter of the…

  3. Mild recessive mutations in six Fraser syndrome-related genes cause isolated congenital anomalies of the kidney and urinary tract.

    PubMed

    Kohl, Stefan; Hwang, Daw-Yang; Dworschak, Gabriel C; Hilger, Alina C; Saisawat, Pawaree; Vivante, Asaf; Stajic, Natasa; Bogdanovic, Radovan; Reutter, Heiko M; Kehinde, Elijah O; Tasic, Velibor; Hildebrandt, Friedhelm

    2014-09-01

    Congenital anomalies of the kidney and urinary tract (CAKUT) account for approximately 40% of children with ESRD in the United States. Hitherto, mutations in 23 genes have been described as causing autosomal dominant isolated CAKUT in humans. However, >90% of cases of isolated CAKUT still remain without a molecular diagnosis. Here, we hypothesized that genes mutated in recessive mouse models with the specific CAKUT phenotype of unilateral renal agenesis may also be mutated in humans with isolated CAKUT. We applied next-generation sequencing technology for targeted exon sequencing of 12 recessive murine candidate genes in 574 individuals with isolated CAKUT from 590 families. In 15 of 590 families, we identified recessive mutations in the genes FRAS1, FREM2, GRIP1, FREM1, ITGA8, and GREM1, all of which function in the interaction of the ureteric bud and the metanephric mesenchyme. We show that isolated CAKUT may be caused partially by mutations in recessive genes. Our results also indicate that biallelic missense mutations in the Fraser/MOTA/BNAR spectrum genes cause isolated CAKUT, whereas truncating mutations are found in the multiorgan form of Fraser syndrome. The newly identified recessive biallelic mutations in these six genes represent the molecular cause of isolated CAKUT in 2.5% of the 590 affected families in this study.

  4. Inheritance of thelytoky in the honey bee Apis mellifera capensis

    PubMed Central

    Chapman, N C; Beekman, M; Allsopp, M H; Rinderer, T E; Lim, J; Oxley, P R; Oldroyd, B P

    2015-01-01

    Asexual reproduction via thelytokous parthenogenesis is widespread in the Hymenoptera, but its genetic underpinnings have been described only twice. In the wasp Lysiphlebus fabarum and the Cape honey bee Apis mellifera capensis the origin of thelytoky have each been traced to a single recessive locus. In the Cape honey bee it has been argued that thelytoky (th) controls the thelytoky phenotype and that a deletion of 9 bp in the flanking intron downstream of exon 5 (tae) of the gemini gene switches parthenogenesis from arrhenotoky to thelytoky. To further explore the mode of inheritance of thelytoky, we generated reciprocal backcrosses between thelytokous A. m. capensis and the arrhenotokous A. m. scutellata. Ten genetic markers were used to identify 108 thelytokously produced offspring and 225 arrhenotokously produced offspring from 14 colonies. Patterns of appearance of thelytokous parthenogenesis were inconsistent with a single locus, either th or tae, controlling thelytoky. We further show that the 9 bp deletion is present in the arrhenotokous A. m. scutellata population in South Africa, in A. m. intermissa in Morocco and in Africanized bees from Brazil and Texas, USA, where thelytoky has not been reported. Thus the 9 bp deletion cannot be the cause of thelytoky. Further, we found two novel tae alleles. One contains the previously described 9 bp deletion and an additional deletion of 7 bp nearby. The second carries a single base insertion with respect to the wild type. Our data are consistent with the putative th locus increasing reproductive capacity. PMID:25585920

  5. Periosteum as a lateral pedicle graft for the treatment of single tooth root recession: A novel approach.

    PubMed

    Kumar, Avadhesh; Kaushal, Shalini; Verma, Neelu; Chandra, Deepti

    2016-01-01

    The treatment of gingival recession defects is indicated for esthetic and functional reasons to reduce root sensitivity, to remove muscle pull, to create or augment keratinized tissue, and to prevent disease progression. The presence of sufficient amount of periosteum adjacent to gingival recession defects makes it a suitable graft. The adult human periosteum is a highly vascular connective tissue with immense regenerative potential. It contains fibroblasts, osteogenic progenitor cells, and stem cells as a result of which it has the ability to differentiate into fibroblast, osteoblast, chondrocytes, adipocytes, and skeletal myocytes. The tissue provided by these cells includes cementum with periodontal ligament fibers and bone. Therefore, in the present case, periosteum has been used as a lateral pedicle graft for the coverage of the single tooth gingival recession (mandibular central incisor). The procedure is justified by the evidence that periosteum is capable of proliferation and osteogenesis after injury.

  6. Analysis of exome sequence in 604 trios for recessive genotypes in schizophrenia

    PubMed Central

    Rees, E; Kirov, G; Walters, J T; Richards, A L; Howrigan, D; Kavanagh, D H; Pocklington, A J; Fromer, M; Ruderfer, D M; Georgieva, L; Carrera, N; Gormley, P; Palta, P; Williams, H; Dwyer, S; Johnson, J S; Roussos, P; Barker, D D; Banks, E; Milanova, V; Rose, S A; Chambert, K; Mahajan, M; Scolnick, E M; Moran, J L; Tsuang, M T; Glatt, S J; Chen, W J; Hwu, H-G; Faraone, Stephen V; Roe, Cheri A; Chandler, Sharon D; Liu, Chih-Min; Liu, Chen-Chung; Yeh, Ling-Ling; Ouyang, Wen-Chen; Chan, Hung-Yu; Chen, Chun-Ying; Neale, B M; Palotie, A; Sklar, P; Purcell, S M; McCarroll, S A; Holmans, P; Owen, M J; O'Donovan, M C

    2015-01-01

    Genetic associations involving both rare and common alleles have been reported for schizophrenia but there have been no systematic scans for rare recessive genotypes using fully phased trio data. Here, we use exome sequencing in 604 schizophrenia proband–parent trios to investigate the role of recessive (homozygous or compound heterozygous) nonsynonymous genotypes in the disorder. The burden of recessive genotypes was not significantly increased in probands at either a genome-wide level or in any individual gene after adjustment for multiple testing. At a system level, probands had an excess of nonsynonymous compound heterozygous genotypes (minor allele frequency, MAF ⩽1%) in voltage-gated sodium channels (VGSCs; eight in probands and none in parents, P=1.5 × 10−4). Previous findings of multiple de novo loss-of-function mutations in this gene family, particularly SCN2A, in autism and intellectual disability provide biological and genetic plausibility for this finding. Pointing further to the involvement of VGSCs in schizophrenia, we found that these genes were enriched for nonsynonymous mutations (MAF ⩽0.1%) in cases genotyped using an exome array, (5585 schizophrenia cases and 8103 controls), and that in the trios data, synaptic proteins interacting with VGSCs were also enriched for both compound heterozygosity (P=0.018) and de novo mutations (P=0.04). However, we were unable to replicate the specific association with compound heterozygosity at VGSCs in an independent sample of Taiwanese schizophrenia trios (N=614). We conclude that recessive genotypes do not appear to make a substantial contribution to schizophrenia at a genome-wide level. Although multiple lines of evidence, including several from this study, suggest that rare mutations in VGSCs contribute to the disorder, in the absence of replication of the original findings regarding compound heterozygosity, this conclusion requires evaluation in a larger sample of trios. PMID:26196440

  7. A Simple Analysis of an Inherited Trait

    ERIC Educational Resources Information Center

    Aagaard, Stanley; Keller, Elhannan

    1977-01-01

    Described is a classroom activity for analyzing an inherited human trait, the ability to tast phenylthiocarbamide (PTC). Formulas for analyzing gene frequency are given for classroom and neighborhood samples. Additional tables include statistics on the ability to taste PTC and other easily sampled human traits. (MA)

  8. Phylogenetics Exercise Using Inherited Human Traits

    ERIC Educational Resources Information Center

    Tuimala, Jarno

    2006-01-01

    A bioinformatics laboratory exercise based on inherited human morphological traits is presented. It teaches how morphological characters can be used to study the evolutionary history of humans using parsimony. The exercise can easily be used in a pen-and-paper laboratory, but if computers are available, a more versatile analysis can be carried…

  9. Epigenetic Inheritance of Disease and Disease Risk

    PubMed Central

    Bohacek, Johannes; Mansuy, Isabelle M

    2013-01-01

    Epigenetic marks in an organism can be altered by environmental factors throughout life. Although changes in the epigenetic code can be positive, some are associated with severe diseases, in particular, cancer and neuropsychiatric disorders. Recent evidence has indicated that certain epigenetic marks can be inherited, and reshape developmental and cellular features over generations. This review examines the challenging possibility that epigenetic changes induced by environmental factors can contribute to some of the inheritance of disease and disease risk. This concept has immense implications for the understanding of biological functions and disease etiology, and provides potential novel strategies for diagnosis and treatment. Examples of epigenetic inheritance relevant to human disease, such as the detrimental effects of traumatic stress or drug/toxic exposure on brain functions, are reviewed. Different possible routes of transmission of epigenetic information involving the germline or germline-independent transfer are discussed, and different mechanisms for the maintenance and transmission of epigenetic information like chromatin remodeling and small noncoding RNAs are considered. Future research directions and remaining major challenges in this field are also outlined. Finally, the adaptive value of epigenetic inheritance, and the cost and benefit of allowing acquired epigenetic marks to persist across generations is critically evaluated. PMID:22781843

  10. Difficulties in Learning Inheritance and Polymorphism

    ERIC Educational Resources Information Center

    Liberman, Neomi; Beeri, Catriel; Kolikant, Yifat Ben-David

    2011-01-01

    This article reports on difficulties related to the concepts of inheritance and polymorphism, expressed by a group of 22 in-service CS teachers with an experience with the procedural paradigm, as they coped with a course on OOP. Our findings are based on the analysis of tests, questionnaires that the teachers completed in the course, as well as on…

  11. Understanding Genetics and Inheritance in Rural Schools

    ERIC Educational Resources Information Center

    Kibuka-Sebitosi, Esther

    2007-01-01

    Conducted in urban and rural schools in two provinces of South Africa, the present study reports biology learners' understanding of concepts about genetics and inheritance. Participants were Grade 11 and 12 learners, aged 15-16 years. The tools included a written questionnaire, interviews, pre- and post-paper and pencil tests and focus group…

  12. The inheritance of acquired epigenetic variations.

    PubMed

    Jablonka, Eva; Lamb, Marion J

    2015-08-01

    There is evidence that the functional history of a gene in one generation can influence its expression in the next. In somatic cells, changes in gene activity are frequently associated with changes in the pattern of methylation of the cytosines in DNA; these methylation patterns are stably inherited. Recent work suggests that information about patterns of methylation and other epigenetic states can also be transmitted from parents to offspring. This evidence is the basis of a model for the inheritance of acquired epigenetic variations. According to the model, an environmental stimulus can induce heritable chromatin modifications which are very specific and predictable, and might result in an adaptive response to the stimulus. This type of response probably has most significance for adaptive evolution in organisms such as fungi and plants, which lack distinct segregation of the soma and germ line. However, in all organisms, the accumulation of specific and random chromatin modifications in the germ line may be important in speciation, because these modifications could lead to reproductive isolation between populations. Heritable chromatin variations may also alter the frequency and distribution of classical mutations and meiotic recombination. Therefore, inherited epigenetic changes in the structure of chromatin can influence neo-Darwinian evolution as well as cause a type of "Lamarckian" inheritance.

  13. The genetics of inherited macular dystrophies

    PubMed Central

    Michaelides, M; Hunt, D; Moore, A

    2003-01-01

    The aim of this paper is to review current knowledge relating to the monogenic macular dystrophies, with discussion of currently mapped genes, chromosomal loci and genotype-phenotype relationships. Inherited systemic disorders with a macular dystrophy component will not be discussed. PMID:12960208

  14. A Study on the Genetic Inheritance of Ankyloglossia Based on Pedigree Analysis

    PubMed Central

    Han, Soo-Hyung; Choi, Yun-Seok; Lim, Jin-Soo; Han, Ki-Taik

    2012-01-01

    Background Ankyloglossia or tongue-tie is a congenital anomaly characterized by an abnormally short lingual frenum. Its prevalence in the newborn population is approximately 4%. Its mode of inheritance has been studied in some articles, but no conclusion has been established. Also, no relevant report has been published in Korea. This study was conducted to elucidate the genetic inheritance of ankyloglossia via pedigree analysis. Methods In this study, 149 patients with no other congenital anomaly who underwent frenuloplasty between March 2001 and March 2010 were studied. Pedigrees were made via pre- or post-operative history taking, and patients with uncertain histories were excluded. In the patient group that showed a hereditary nature, the male-to-female ratio, inheritance rate, and pattern of inheritance were investigated. Results One hundred (67.11%) of the patients were male and 49 (32.89%) were female (male-female ratio=2.04:1). Ninety-one (61.07%) patients reported no other relative with ankyloglossia, and 58 (38.93%) patients had a relative with this disease. The inheritance rate was 20.69% in the 58 cases with a hereditary nature. In the group with no family history of ankyloglossia, the male-female ratio was 3.79:1, which significantly differed from that of the group with a family history of ankyloglossia. X-chromosome mediated inheritance and variation in the gene expression was revealed in the pedigree drawn for the groups with hereditary ankyloglossia. Conclusions Ankyloglossia has a significant hereditary nature. Our data suggest X-linked inheritance. This study with 149 patients, the first in Korea, showed X-linked inheritance in patients with a sole anomaly. PMID:22872835

  15. Clinical and molecular characterization of seven Egyptian families with autosomal recessive robinow syndrome: Identification of four novel ROR2 gene mutations.

    PubMed

    Aglan, Mona; Amr, Khalda; Ismail, Samira; Ashour, Adel; Otaify, Ghada A; Mehrez, Mennat Allah I; Aboul-Ezz, Eman H A; El-Ruby, Mona; Mazen, Inas; Abdel-Hamid, Mohamed S; Temtamy, Samia A

    2015-12-01

    Robinow syndrome (RS) is a rare genetic disorder characterized by limb shortening, genital hypoplasia, and craniofacial/orodental abnormalities. The syndrome follows both autosomal dominant and recessive patterns of inheritance with similar phenotypic presentation and overlapping features. Autosomal recessive Robinow syndrome (ARRS) is caused by mutations in the ROR2 gene. Here, we present the clinical, radiological and molecular findings of 11 Egyptian patients from 7 unrelated consanguineous families with clinical features of ARRS. Mutation analyses of ROR2 gene identified five pathogenic mutations distributed all over the gene. The identified mutations included four novel (G326A, D166H, S677F, and R528Q) and one previously reported (Y192D). Our results extend the number of ROR2 mutations identified so far, suggest a founder effect in the Egyptian population, and emphasize the important role of genetic testing in proper counseling and patients' management.

  16. The frissonnant mutant mouse, a model of dopamino-sensitive, inherited motor syndrome.

    PubMed

    Callizot, N; Guénet, J L; Baillet, C; Warter, J M; Poindron, P

    2001-06-01

    The frissonnant (fri) mutation is an autosomic recessive mutation which spontaneously appeared in the stock of C3H mice. fri mutant mice have locomotor instability and rapid tremor. Since tremor ceases when mutant mice have sleep or are anaesthetized, and because of their obvious stereotyped motor behavior, these mice could represent an inherited Parkinsonian syndrome. We show here that the fri/fri mouse fulfills two out of the three criteria required to validate an experimental model of human disease, that is isomorphism, homology and predictivity. Indeed, fri/fri mice present an important motor deficit accompanying visible tremor and stereotypies. They display some memory deficits as in human Parkinson's desease. l-Dopa and apomorphine (dopaminergic agonists), ropinirole (selective D2 agonist), and selegiline (an monoamino-oxidase B [MAO-B] inhibitor) improve their clinical status. However, neither anatomopathological evidence of nigrostriatal lesion, nor decrease in tyrosine hydroxylase production could be seen.

  17. Disruptions in asymmetric centrosome inheritance and WDR62-Aurora kinase B interactions in primary microcephaly

    PubMed Central

    Sgourdou, Paraskevi; Mishra-Gorur, Ketu; Saotome, Ichiko; Henagariu, Octavian; Tuysuz, Beyhan; Campos, Cynthia; Ishigame, Keiko; Giannikou, Krinio; Quon, Jennifer L.; Sestan, Nenad; Caglayan, Ahmet O.; Gunel, Murat; Louvi, Angeliki

    2017-01-01

    Recessive mutations in WD repeat domain 62 (WDR62) cause microcephaly and a wide spectrum of severe brain malformations. Disruption of the mouse ortholog results in microcephaly underlain by reduced proliferation of neocortical progenitors during late neurogenesis, abnormalities in asymmetric centrosome inheritance leading to neuronal migration delays, and altered neuronal differentiation. Spindle pole localization of WDR62 and mitotic progression are defective in patient-derived fibroblasts, which, similar to mouse neocortical progenitors, transiently arrest at prometaphase. Expression of WDR62 is closely correlated with components of the chromosome passenger complex (CPC), a key regulator of mitosis. Wild type WDR62, but not disease-associated mutant forms, interacts with the CPC core enzyme Aurora kinase B and staining of CPC components at centromeres is altered in patient-derived fibroblasts. Our findings demonstrate critical and diverse functions of WDR62 in neocortical development and provide insight into the mechanisms by which its disruption leads to a plethora of structural abnormalities. PMID:28272472

  18. De novo and inherited deletions of the 5q13 region in spinal muscular atrophies

    SciTech Connect

    Melki, J.; Lefebvre, S.; Burglen, L.; Burlet, P.; Clermont, O.; Reboullet, S.; Benichou, B.; Zeviani, M. ); Millasseau, P. ); Le Paslier, D. )

    1994-06-03

    Spinal muscular atrophies (SMAs) represent the second most common fatal autosomal recessive disorder after cystic fibrosis. Childhood spinal muscular atrophies are divided into severe (type I) and mild forms (types II and III). By a combination of genetic and physical mapping, a yeast artificial chromosome contig of the 5q13 region spanning the disease locus was constructed that showed the presence of low copy repeats in this region. Allele segregation was analyzed at the closest genetic loci detected by markers C212 and C272 in 201 SMA families. Inherited and de novo deletions were observed in nine unrelated SMA patients. Moreover, deletions were strongly suggested in at least 18 percent of SMA type I patients by the observation of marked heterozygosity deficiency for the loci studied. These results indicate that deletion events are statistically associated with the severe form of spinal muscular atrophy. 25 refs., 5 figs.

  19. Management of the Spring Snowmelt Recession in Regulated Systems

    NASA Astrophysics Data System (ADS)

    Yarnell, S. M.; Lind, A.; Epke, G.; Viers, J. H.

    2013-12-01

    In unregulated rivers in the Sierra Nevada mountains of California, the spring snowmelt recession links high winter flows to low summer baseflow and is a consistent and predictable portion of the annual hydrograph. Consequently, it is an important resource to both riverine ecosystems and California's water supply. In regulated river systems where the spring snowmelt recession is often captured behind dams or diverted for hydropower, restoration of a more natural spring flow regime can provide distinct ecological benefits, such as breeding and migration cues for native species, increased habitat availability, and greater hydraulic habitat diversity. However, knowledge of how to create and manage an ecologically beneficial spring snowmelt recession in a regulated river system has been lacking. This study defined a methodology by which spring flow regimes can be modeled in regulated systems from the quantifiable characteristics of spring snowmelt recessions in unregulated rivers. Using fundamental flow components such as magnitude, timing, and rate of change, the spring snowmelt recession in eight unregulated rivers across the Sierra Nevada range was quantified to gain a better understanding of the predictability and variability across watersheds. The analysis found that unregulated Sierran systems behaved similarly with respect to seasonal patterns and flow recession shape (i.e., recession limb curvature), and thus flows could be modeled in a manner that mimics those predictable characteristics. Using this methodology that quantifies spring recession flows in terms of a daily percent decrease in flow, a series of flow recession scenarios were then created for application on a regulated Sierran river. Four scenarios, ranging from a slow natural recession to a short fast recession typically observed in regulated rivers following cessation of high flow spills, were evaluated within a 2D hydrodynamic model. The effects of the flows on suitable habitat for Foothill yellow

  20. Mutations in CAPN1 Cause Autosomal-Recessive Hereditary Spastic Paraplegia

    PubMed Central

    Gan-Or, Ziv; Bouslam, Naima; Birouk, Nazha; Lissouba, Alexandra; Chambers, Daniel B.; Vérièpe, Julie; Androschuck, Alaura; Laurent, Sandra B.; Rochefort, Daniel; Spiegelman, Dan; Dionne-Laporte, Alexandre; Szuto, Anna; Liao, Meijiang; Figlewicz, Denise A.; Bouhouche, Ahmed; Benomar, Ali; Yahyaoui, Mohamed; Ouazzani, Reda; Yoon, Grace; Dupré, Nicolas; Suchowersky, Oksana; Bolduc, Francois V.; Parker, J. Alex; Dion, Patrick A.; Drapeau, Pierre; Rouleau, Guy A.; Bencheikh, Bouchra Ouled Amar

    2016-01-01

    Hereditary spastic paraplegia (HSP) is a genetically and clinically heterogeneous disease characterized by spasticity and weakness of the lower limbs with or without additional neurological symptoms. Although more than 70 genes and genetic loci have been implicated in HSP, many families remain genetically undiagnosed, suggesting that other genetic causes of HSP are still to be identified. HSP can be inherited in an autosomal-dominant, autosomal-recessive, or X-linked manner. In the current study, we performed whole-exome sequencing to analyze a total of nine affected individuals in three families with autosomal-recessive HSP. Rare homozygous and compound-heterozygous nonsense, missense, frameshift, and splice-site mutations in CAPN1 were identified in all affected individuals, and sequencing in additional family members confirmed the segregation of these mutations with the disease (spastic paraplegia 76 [SPG76]). CAPN1 encodes calpain 1, a protease that is widely present in the CNS. Calpain 1 is involved in synaptic plasticity, synaptic restructuring, and axon maturation and maintenance. Three models of calpain 1 deficiency were further studied. In Caenorhabditis elegans, loss of calpain 1 function resulted in neuronal and axonal dysfunction and degeneration. Similarly, loss-of-function of the Drosophila melanogaster ortholog calpain B caused locomotor defects and axonal anomalies. Knockdown of calpain 1a, a CAPN1 ortholog in Danio rerio, resulted in abnormal branchiomotor neuron migration and disorganized acetylated-tubulin axonal networks in the brain. The identification of mutations in CAPN1 in HSP expands our understanding of the disease causes and potential mechanisms. PMID:27153400

  1. A homozygous mutation in TRIM36 causes autosomal recessive anencephaly in an Indian family.

    PubMed

    Singh, Nivedita; Kumble Bhat, Vishwanath; Tiwari, Ankana; Kodaganur, Srinivas G; Tontanahal, Sagar J; Sarda, Astha; Malini, K V; Kumar, Arun

    2017-01-13

    Anencephaly is characterized by the absence of brain tissues and cranium. During primary neurulation stage of the embryo, the rostral part of the neural pore fails to close, leading to anencephaly. Anencephaly shows a heterogeneous etiology, ranging from environmental to genetic causes. The autosomal recessive inheritance of anencephaly has been reported in several populations. In this study, we employed whole-exome sequencing and identified a homozygous missense mutation c.1522C>A (p.Pro508Thr) in the TRIM36 gene as the cause of autosomal recessive anencephaly (APH) in an Indian family. The TRIM36 gene is expressed in the developing brain, suggesting a role in neurogenesis. In silco analysis showed that proline at codon position 508 is highly conserved in 26 vertebrate species, and the mutation is predicted to affect the conformation of the B30.2/SPRY domain of TRIM36. Both in vitro and in vivo results showed that the mutation renders the TRIM36 protein less stable. TRIM36 is known to associate with microtubules. Transient expression of the mutant TRIM36 in HeLa and LN229 cells resulted in microtubule disruption, disorganized spindles, loosely arranged chromosomes, multiple spindles, abnormal cytokinesis, reduced cell proliferation and increased apoptosis as compared to cells transfected with its wild-type counterpart. The siRNA knock down of TRIM36 in HeLa and LN229 cells also led to reduced cell proliferation and increased apoptosis. We suggest that microtubule disruption and disorganized spindles mediated by mutant TRIM36 affect neural cell proliferation during neural tube formation, leading to anencephaly.

  2. Elevated c-myc protooncogene expression in autosomal recessive polycystic kidney disease

    SciTech Connect

    Cowley, B.D. Jr.; Smardo, F.L. Jr.; Grantham, J.J.; Calvet, J.P.

    1987-12-01

    The polycystic kidney diseases (PKDs) are a group of disorders characterized by the growth of epithelial cysts from the nephrons and collecting ducts of kidney tubules. The diseases can be inherited or can be provoked by environmental factors. To investigate the molecular basis of the abnormal cell growth associated with PKD, c-myc protooncogene expression was studied in a mouse model for autosomal recessive PKD. Homozygous recessive C57BL/6J (cpk/cpk) mice develop massively enlarged cystic kidneys and die from renal failure shortly after 3 weeks of age. Quantitative dot blot and RNA blot hybridization experiments in which whole kidney poly(A)/sup +/ RNA was hybridized with a c-myc RNA probe showed a 2- to 6-fold increase in c-myc mRNA at 2 weeks, and a 25- to 30-fold increase in c-myc mRNA at 3 weeks of age in polycystic mice, as compared to normal littermates. c-myc expression was also examined under two conditions in which kidney cell growth was experimentally induced in normal adult mice: compensatory renal hypertrophy and tubule regeneration following folic acid-induced renal cell injury. While compensatory hypertrophy resulted in only a small increase in c-myc, folic acid treatment gave rise after 24 hr to a 12-fold increase in c-myc RNA. The induction of c-myc by folic acid is consistent with increased cellular proliferation regenerating tubules. In contrast, polycystic kidneys show only a minimal increase in cellular proliferation over that seen in normal kidneys, while c-myc levels were found to be markedly elevated. Thus, the level of c-myc expression in cystic kidneys appears to be out of proportion to the rate of cell division, suggesting that elevated and potentially abnormal c-myc expression may be involved in the pathogenesis of PKD.

  3. Precarious Slopes? The Great Recession, Federal Stimulus, and New Jersey Schools. Working Paper #02-12

    ERIC Educational Resources Information Center

    Chakrabarti, Rajashri; Sutherland, Sarah

    2012-01-01

    While sparse literature exists investigating the impact of the Great Recession on various sectors of the economy, there is virtually no research that studies the effect of the Great Recession, or past recessions, on schools. This paper starts to fill the void. Studying school funding during the recession is of paramount importance because schools…

  4. Inherited and acquired immunodeficiencies underlying tuberculosis in childhood

    PubMed Central

    Boisson-Dupuis, Stéphanie; Bustamante, Jacinta; El-Baghdadi, Jamila; Camcioglu, Yildiz; Parvaneh, Nima; Azbaoui, Safaa El; Agader, Aomar; Hassani, Amal; Hafidi, Naima El; Mrani, Nidal Alaoui; Jouhadi, Zineb; Ailal, Fatima; Najib, Jilali; Reisli, Ismail; Zamani, Adil; Yosunkaya, Sebnem; Gulle-Girit, Saniye; Yildiran, Alisan; Cipe, Funda Erol; Torun, Selda Hancerli; Metin, Ayse; Atikan, Basak Yildiz; Hatipoglu, Nevin; Aydogmus, Cigdem; Kilic, Sara Sebnem; Dogu, Figen; Karaca, Neslihan; Aksu, Guzide; Kutukculer, Necil; Keser-Emiroglu, Melike; Somer, Ayper; Tanir, Gonul; Aytekin, Caner; Adimi, Parisa; Mahdaviani, Seyed Alireza; Mamishi, Setareh; Bousfiha, Aziz; Sanal, Ozden; Mansouri, Davood; Casanova, Jean-Laurent; Abel, Laurent

    2015-01-01

    Summary Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb) and a few related mycobacteria, is a devastating disease, killing more than a million individuals per year worldwide. However, its pathogenesis remains largely elusive, as only a small proportion of infected individuals develop clinical disease either during primary infection or during reactivation from latency or secondary infection. Subacute, hematogenous, and extrapulmonary disease tends to be more frequent in infants, children, and teenagers than in adults. Life-threatening primary TB of childhood can result from known acquired or inherited immunodeficiencies, although the vast majority of cases remain unexplained. We review here the conditions conferring a predisposition to childhood clinical diseases caused by mycobacteria, including not only M.tb but also weakly virulent mycobacteria, such as BCG vaccines and environmental mycobacteria. Infections with weakly virulent mycobacteria are much rarer than TB, but the inherited and acquired immunodeficiencies underlying these infections are much better known. Their study has also provided genetic and immunological insights into childhood TB, as illustrated by the discovery of single-gene inborn errors of IFN-γ immunity underlying severe cases of TB. Novel findings are expected from ongoing and future human genetic studies of childhood TB in countries that combine a high proportion of consanguineous marriages, a high incidence of TB, and an excellent clinical care, such as Iran, Morocco, and Turkey. PMID:25703555

  5. The inheritance of organelle genes and genomes: patterns and mechanisms.

    PubMed

    Xu, Jianping

    2005-12-01

    Unlike nuclear genes and genomes, the inheritance of organelle genes and genomes does not follow Mendel's laws. In this mini-review, I summarize recent research progress on the patterns and mechanisms of the inheritance of organelle genes and genomes. While most sexual eukaryotes show uniparental inheritance of organelle genes and genomes in some progeny at least part of the time, increasing evidence indicates that strictly uniparental inheritance is rare and that organelle inheritance patterns are very diverse and complex. In contrast with the predominance of uniparental inheritance in multicellular organisms, organelle genes in eukaryotic microorganisms, such as protists, algae, and fungi, typically show a greater diversity of inheritance patterns, with sex-determining loci playing significant roles. The diverse patterns of inheritance are matched by the rich variety of potential mechanisms. Indeed, many factors, both deterministic and stochastic, can influence observed patterns of organelle inheritance. Interestingly, in multicellular organisms, progeny from interspecific crosses seem to exhibit more frequent paternal leakage and biparental organelle genome inheritance than those from intraspecific crosses. The recent observation of a sex-determining gene in the basidiomycete yeast Cryptococcus neoformans, which controls mitochondrial DNA inheritance, has opened up potentially exciting research opportunities for identifying specific molecular genetic pathways that control organelle inheritance, as well as for testing evolutionary hypotheses regarding the prevalence of uniparental inheritance of organelle genes and genomes.

  6. Elusive inheritance: Transgenerational effects and epigenetic inheritance in human environmental disease.

    PubMed

    Martos, Suzanne N; Tang, Wan-Yee; Wang, Zhibin

    2015-07-01

    Epigenetic mechanisms involving DNA methylation, histone modification, histone variants and nucleosome positioning, and noncoding RNAs regulate cell-, tissue-, and developmental stage-specific gene expression by influencing chromatin structure and modulating interactions between proteins and DNA. Epigenetic marks are mitotically inherited in somatic cells and may be altered in response to internal and external stimuli. The idea that environment-induced epigenetic changes in mammals could be inherited through the germline, independent of genetic mechanisms, has stimulated much debate. Many experimental models have been designed to interrogate the possibility of transgenerational epigenetic inheritance and provide insight into how environmental exposures influence phenotypes over multiple generations in the absence of any apparent genetic mutation. Unexpected molecular evidence has forced us to reevaluate not only our understanding of the plasticity and heritability of epigenetic factors, but of the stability of the genome as well. Recent reviews have described the difference between transgenerational and intergenerational effects; the two major epigenetic reprogramming events in the mammalian lifecycle; these two events making transgenerational epigenetic inheritance of environment-induced perturbations rare, if at all possible, in mammals; and mechanisms of transgenerational epigenetic inheritance in non-mammalian eukaryotic organisms. This paper briefly introduces these topics and mainly focuses on (1) transgenerational phenotypes and epigenetic effects in mammals, (2) environment-induced intergenerational epigenetic effects, and (3) the inherent difficulties in establishing a role for epigenetic inheritance in human environmental disease.

  7. The pouch and tunnel technique for management of multiple gingival recession defects

    PubMed Central

    Dani, Sneha; Dhage, Aditi; Gundannavar, Gayatri

    2014-01-01

    The desire for improved esthetics has increased tremendously over the years. Periodontal plastic surgery deals with regenerative procedures designed to restore form, function and enhance esthetics. The aim of this study was to evaluate the effectiveness of subepithelial connective tissue graft using pouch and tunnel technique as root coverage procedure. Three patients corresponding to a total of 8 sites participated in the study. Maxillary teeth with miller's class I gingival recession were included in the study. All the sites were treated using subepithelial connective tissue graft using pouch and tunneling technique. Patients were followed up for a period of 6 months and 1 year. All the treated teeth showed 100% root coverage at the end of 6 months and 1 year. Gingival recession is a common occurrence and its prevalence increases with age. It can lead to clinical problems, diminished cosmetic appeal and hence esthetic concern. There are various techniques for root coverage. Subepithelial connective tissue graft has shown the best predictability (95%) of root coverage in Millers class I & II cases. This technique preserves the intermediate papilla, accelerates the initial wound healing & also applies less traction. Due to minimal trauma at the recipient site, this procedure may be advantageous in treatment of recession as compared to other treatment modalities. PMID:25624637

  8. Suprapedicular Foraminal Endoscopic Approach to Lumbar Lateral Recess Decompression Surgery to Treat Degenerative Lumbar Spinal Stenosis

    PubMed Central

    Wang, Ya-peng; Zhang, Wei; Li, Bao-li; Sun, Ya-peng; Ding, Wen-yuan; Shen, Yong

    2016-01-01

    Background To discuss the strategy of suprapedicular foraminal endoscopic approach to lumbar lateral recess decompression and evaluate the safety and effectiveness of this strategy. Material/Methods Complete clinical information of 52 cases of lumbar lateral recess decompression with therapy of suprapedicular foraminal endoscopic approach were analyzed during the period from February 2010 to April 2014 in the Third Hospital of Hebei. All patients were followed up for 24 months, and VAS, JOA, ODI, and LRD were compared between preoperative and postoperative therapy and changes of FA. Intraoperative and postoperative complications were recorded and the safety of the surgery was evaluated. The surgical “excellent” and “good” rates were evaluated using MacNab score. Results VAS scores for lumbago and leg pain at 3, 6, 12, and 24 months after surgery were significantly lower than before surgery (p<0.05). JOA scores at 12 and 24 months after surgery were significantly higher than before surgery (p<0.05). ODI at 12 and 24 months after surgery were significantly lower than before surgery (p<0.05). LRD after surgery was higher (p<0.05), and FA was lower than before surgery. Conclusions Use of the suprapedicular foraminal endoscopic approach to lumbar lateral recess decompression is safe and effective, and this minimally invasive treatment can achieve satisfactory results, especially for elderly patients with complicated underlying diseases. PMID:27890911

  9. Molecular analysis of the genes causing recessive demyelinating Charcot-Marie-Tooth disease in Japan.

    PubMed

    Hayashi, Makiko; Abe, Akiko; Murakami, Tatsufumi; Yamao, Satoshi; Arai, Hidee; Hattori, Hideji; Iai, Mizue; Watanabe, Kyoko; Oka, Nobuyuki; Chida, Keiji; Kishikawa, Yumiko; Hayasaka, Kiyoshi

    2013-05-01

    Charcot-Marie-Tooth disease (CMT), the most common hereditary neuropathy, has been classified into two types, demyelinating and axonal types. We previously analyzed the genes causing dominant demyelinating CMT in 227 Japanese patients to identify the genetic background, but could not find any mutations in 110 patients. To investigate the frequency of patients with autosomal recessive demyelinating CMT (CMT4) mutations, we analyzed the coding sequence of known causative genes of CMT4 in 103 demyelinating CMT patients, excluding seven patients owing to lack of specimens. We found one patient with a GDAP1 mutation, one patient with an MTMR2 mutation, two patients with SH3TC2/KIAA1985 mutations and three patients with FGD4 mutations. Twelve patients, including five previously detected patients with PRX mutations, were diagnosed as CMT4, accounting for 5.5% of demyelinating CMT. In the patient with GDAP1 mutation, only one mutation inherited from his mother was detected by genomic sequencing. Analysis by reverse transcription polymerase chain reaction using messenger RNA (mRNA) from the patient's leukocytes revealed the absence of transcription from the allele inherited from his father, suggesting the existence of one more mutation leading to a lack or destabilization of mRNA. Most patients carrying CMT4 gene mutations present with early-onset and slowly progressive symptoms, which may be associated with the function of mutants. We could not identify the disease-causing gene in 96 patients (about 45%). Further studies including studies with next-generation sequencers will be required to identify the causative gene in Japanese CMT.

  10. Inheritance of resistance to zucchini yellow mosaic virus and watermelon mosaic virus in watermelon.

    PubMed

    Xu, Y; Kang, D; Shi, Z; Shen, H; Wehner, T

    2004-01-01

    High resistance to zucchini yellow mosaic virus-China strain (ZYMV-CH) and moderate resistance to watermelon mosaic virus (WMV) were found in a selection of PI 595203 (Citrullus lanatus var. lanatus), an Egusi type originally collected in Nigeria. Mixed inoculations showed primarily that these two viruses have no cross-protection. This fact may explain the high frequency of mixed infection often observed in commercial fields. When plants were inoculated with a mixture of the two viruses, the frequency of plants resistant to ZYMV was lower than expected, indicating that WMV infection may reduce the ability of a plant to resist ZYMV. We studied inheritance of resistance to ZYMV-CH and WMV, using crosses between a single-plant selection of PI 595203 and the ZYMV-susceptible watermelon inbreds 9811 and 98R. According to virus ratings of the susceptible parents, the resistant parent, and the F1, F2, and BC1 generations, resistance to ZYMV-CH was conferred by a single recessive gene, for which the symbol zym-CH is suggested. The high tolerance to WMV was controlled by at least two recessive genes.

  11. The effects of extensional inheritance on transtensional deformation patterns

    NASA Astrophysics Data System (ADS)

    Naliboff, J.; Buiter, S. J.; Le Pourhiet, L.; May, D.

    2015-12-01

    Continental rifting and breakup frequently occurs through multiple phases of extension in which margin architecture is governed by distinct modes of brittle and viscous deformation, as well as surface processes. Transitions between such phases of extension may in some cases reflect plate-scale changes in extension obliquity and velocity. For example, recent studies indicate that localization of transtensional deformation onto a narrow shear zone in the Gulf of California Rift corresponds temporally with an increase in rift obliquity. Here, we use high-resolution 3-D models (run with pTatin3D) to examine how transtensional deformation patterns evolve with such increases in extension obliquity. Our models build on previous crustal-scale analogue and numerical studies examining oblique reactivation of normal faults. These studies show that the orientation and strength of inherited normal faults strongly control the style of slip and deformation partitioning between new and reactivated faults. While highly insightful, these studies examine deformation over limited spatial extents and do not account for key processes such as isostasy and temperature-dependent rock strength. Here, we model the thermal-mechanical evolution of the lithosphere and asthenosphere to a depth of 200 km. Deformation occurs through an initial phase of orthogonal, Basin and Range style extension, followed by 1-2 phases of extension at different obliquities. The initial lithospheric structure and time-dependent boundary conditions follow geologic observations and plate-reconstructions within the Gulf of California. Our experiments highlight the strong control of inheritance on transtensional crustal deformation. By comparing fault development, crustal thickness evolution and block rotations directly with observations from the Gulf of California and other extensional and transtensional regions, we can better evaluate the relative control of structural inheritance on passive margin architecture.

  12. Association between inherited monogenic liver disorders and chronic hepatitis C

    PubMed Central

    Piekuse, Linda; Kreile, Madara; Zarina, Agnese; Steinberga, Zane; Sondore, Valentina; Keiss, Jazeps; Lace, Baiba; Krumina, Astrida

    2014-01-01

    AIM: To determine the frequencies of mutations that cause inherited monogenic liver disorders in patients with chronic hepatitis C. METHODS: This study included 86 patients with chronic hepatitis C (55 men, 31 women; mean age at diagnosis, 38.36 ± 14.52 years) who had undergone antiviral therapy comprising pegylated interferon and ribavirin. Viral load, biochemical parameter changes, and liver biopsy morphological data were evaluated in all patients. The control group comprised 271 unrelated individuals representing the general population of Latvia for mutation frequency calculations. The most frequent mutations that cause inherited liver disorders [gene (mutation): ATP7B (H1069Q), HFE (C282Y, H63D), UGT1A1 (TA)7, and SERPINA1 (PiZ)] were detected by polymerase chain reaction (PCR), bidirectional PCR allele-specific amplification, restriction fragment length polymorphism analysis, and sequencing. RESULTS: The viral genotype was detected in 80 of the 86 patients. Viral genotypes 1, 2, and 3 were present in 61 (76%), 7 (9%), and 12 (15%) patients, respectively. Among all 86 patients, 50 (58%) reached an early viral response and 70 (81%) reached a sustained viral response. All 16 patients who did not reach a sustained viral response had viral genotype 1. Case-control analysis revealed a statistically significant difference in only the H1069Q mutation between patients and controls (patients, 0.057; controls, 0.012; odds ratio, 5.514; 95%CI: 1.119-29.827, P = 0.022). However, the H1069Q mutation was not associated with antiviral treatment outcomes or biochemical indices. The (TA) 7 mutation of the UGT1A1 gene was associated with decreased ferritin levels (beta regression coefficient = -295.7, P = 0.0087). CONCLUSION: Genetic mutations that cause inherited liver diseases in patients with hepatitis C should be studied in detail. PMID:24575168

  13. Sex linked recessive dystonia parkinsonism of Panay, Philippines (XDP)

    PubMed Central

    Lee, L V; Munoz, E L; Tan, K T; Reyes, M T

    2001-01-01

    Sex linked dystonia parkinsonism (XDP), also referred to as “lubag” in American literature, was described in 1975 occurring endemically in Panay, Philippines. It is an adult onset, sex linked, predominantly male, severe, progressive movement disorder with high penetrance and a high frequency of generalisation. The movement disorder is characterised by dystonic movements, usually starting in the 3rd or 4th decade, spreading to generalisation within two to five years. The dystonia coexists or is replaced by parkinsonism usually beyond the 10th year of illness. No treatment has been found to be effective. Neuroimaging shows caudate and putamenal atrophy in patients reaching the parkinsonian stage. Neuropathology reveals pronounced atrophy of the caudate and putamen, mostly in the cases with long standing illness. The sex linked pattern of inheritance has been established. Genetic studies have located the affected gene (DYT3) to Xq13.1, with one group mapping the XDP gene to a < 350 kb locus in the DXS 7117–DXS 559 region. PMID:11724910

  14. Inheritance is where physiology meets evolution

    PubMed Central

    Danchin, Étienne; Pocheville, Arnaud

    2014-01-01

    Physiology and evolutionary biology have developed as two separated disciplines, a separation that mirrored the hypothesis that the physiological and evolutionary processes could be decoupled. We argue that non-genetic inheritance shatters the frontier between physiology and evolution, and leads to the coupling of physiological and evolutionary processes to a point where there exists a continuum between accommodation by phenotypic plasticity and adaptation by natural selection. This approach is also profoundly affecting the definition of the concept of phenotypic plasticity, which should now be envisaged as a multi-scale concept. We further suggest that inclusive inheritance provides a quantitative way to help bridging infra-individual (i.e. physiology) with supra-individual (i.e. evolution) approaches, in a way that should help building the long sough inclusive evolutionary synthesis. PMID:24882815

  15. Medical Problems in Obstetrics: Inherited Metabolic Disease.

    PubMed

    Murphy, Elaine

    2015-07-01

    An increasing number of women with rare inherited disorders of metabolism are becoming pregnant. Although, in general, outcomes for women and their children are good, there are a number of issues that need to be considered. Currently, limited specific guidance on the management of these conditions in pregnancy is available. Prepregnancy counselling with information on inheritance, options for reproduction, teratogenicity risk, potential impact on maternal health and long-term health of children should be offered. With appropriate specialist management, the teratogenic risk of conditions such as maternal phenylketonuria (PKU) can be eliminated, and the risk of metabolic decompensation in disorders of energy metabolism or intoxication significantly reduced. Multidisciplinary management, and close liaison between obstetricians and other specialists, is required for those women in whom there is cardiac, renal, respiratory, joint or other organ involvement.

  16. Novel approaches for diagnosing inherited platelet disorders.

    PubMed

    Bastida Bermejo, José María; Hernández-Rivas, Jesús María; González-Porras, José Ramón

    2017-01-20

    Inherited platelet disorders diagnosis is based on the clinical history and bleeding assessment tools. The laboratory functional assays as well as the molecular test to identify the pathogenic genetic variant are essential to confirm the accurate diagnosis of these disorders. Nowadays, the main challenges to developing a new diagnostic system are involved in reducing the samples' volume, and faster and more helpful analysis. Moreover, there are no widely available and standardised global tests. High throughput genetic testing such as next-generation sequencing has revolutionised DNA sequencing technologies as it allows the simultaneous and faster investigation of multiple genes at a manageable cost. This technology has improved the molecular characterisation of inherited platelet disorders and has been implemented in the research studies and the clinical routine practice.

  17. Management of inherited atherogenic dyslipidemias in children.

    PubMed

    Guardamagna, Ornella; Cagliero, Paola; Abello, Francesca

    2013-04-01

    In order to prevent cardiovascular disease, the treatment of inherited dyslipidemias in childhood represents an emerging topic capturing scientists' consideration. A body of findings emerged in the last decade for diagnosis and therapy, and results were recently summarized to introduce new guidelines by the American Academy of Pediatrics and National Institute for Health and Clinical Excellence. It is well known and generally shared the need to detect affected children precociously, when the family history address to genetic dyslipidemia and when familial premature cardiovascular disease occurs. A spectrum of disorders involving lipoproteins could be recognized by specific biochemical and genetic markers. A defined diagnosis represents the starting point to establish a correct treatment and follow-up program. This review represents a literature synthesis of the main cornerstones and criticisms concerning the screening program and management of atherogenic inherited dyslipidemias in children and adolescents.

  18. Dominant and recessive compound heterozygous mutations in epidermolysis bullosa simplex demonstrate the role of the stutter region in keratin intermediate filament assembly.

    PubMed

    Yasukawa, Kana; Sawamura, Daisuke; McMillan, James R; Nakamura, Hideki; Shimizu, Hiroshi

    2002-06-28

    Keratin intermediate filaments are important cytoskeletal structural proteins involved in maintaining cell shape and function. Mutations in the epidermal keratin genes, keratin 5 or keratin 14 lead to the disruption of keratin filament assembly, resulting in an autosomal dominant inherited blistering skin disease, epidermolysis bullosa simplex (EBS). We investigated a large EBS kindred who exhibited a markedly heterogeneous clinical presentation and detected two distinct keratin 5 mutations in the proband, the most severely affected. One missense mutation (E170K) in the highly conserved helix initiation peptide sequence of the 1A rod domain was found in all the affected family members. In contrast, the other missense mutation (E418K) was found only in the proband. The E418K mutation was located in the stutter region, an interruption in the heptad repeat regularity, whose function as yet remains unclear. We hypothesized that this mutated stutter allele was clinically silent when combined with the wild type allele but aggravates the clinical severity of EBS caused by the E170K mutation on the other allele. To confirm this in vitro, we transfected mutant keratin 5 cDNA into cultured cells. Although only 12.7% of the cells transfected with the E170K mutation alone showed disrupted keratin filament aggregations, significantly more cells (30.0%) cotransfected with both E170K and E418K mutations demonstrated keratin aggregation (p < 0.05). These transfection assay results corresponded to the heterogeneous clinical findings of the EBS patient in this kindred. We have identified the first case of both compound heterozygous dominant (E170K) and recessive (E418K) mutations in any keratin gene and confirmed the significant involvement of the stutter region in the assembly and organization of the keratin intermediate filament network in vitro.

  19. Familial heterotaxia: What is the inheritance in this family?

    SciTech Connect

    Delatycki, M.B.; Sheffield, L.J.

    1997-04-14

    Recently, Alonso and colleagues reported on a number of cases of autosomal dominant heterotaxia in the American Journal of Medical Genetics. We would like to report a case of familial heterotaxia whose inheritance is unclear. II-2 and II-3 are sisters married to men who are related neither to themselves nor to each other. III-1 was diagnosed on antenatal ultrasonography as having complex congenital heart disease. Foetal blood sampling was carried out and was normal (46,XX). Postnatally she was found to have a complete atrioventricular septal defect, separate apical VSD, small left ventricle, interrupted inferior vena cava, hypoplastic aortic arch, and aortic coarctation. The child developed necrotising enterocolitis on day 2 and died at age 11 days. Autopsy confirmed these findings; the abdominal organs were all in their normal sites with a single spleen of normal size. 6 refs., 1 fig.

  20. CZ: Multimethods and Multiple Inheritance Without Diamonds

    DTIC Science & Technology

    2009-12-01

    Then, we would use the Scala solution for ensuring that C ’ s constructor is called only once. 15 To solve the multiple dispatch problem, if methods m(B...CZ:Multimethods andMultiple Inheritance Without Diamonds 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR( S ) 5d. PROJECT...NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME( S ) AND ADDRESS(ES) Carnegie Mellon University ,School of Computer

  1. Dog models for blinding inherited retinal dystrophies.

    PubMed

    Petersen-Jones, Simon M; Komáromy, András M

    2015-03-01

    Spontaneous canine models exist for several inherited retinal dystrophies. This review will summarize the models and indicate where they have been used in translational gene therapy trials. The RPE65 gene therapy trials to treat childhood blindness are a good example of how studies in dogs have contributed to therapy development. Outcomes in human clinical trials are compared and contrasted with the result of the preclinical dog trials.

  2. Dog Models for Blinding Inherited Retinal Dystrophies

    PubMed Central

    Komáromy, András M.

    2015-01-01

    Abstract Spontaneous canine models exist for several inherited retinal dystrophies. This review will summarize the models and indicate where they have been used in translational gene therapy trials. The RPE65 gene therapy trials to treat childhood blindness are a good example of how studies in dogs have contributed to therapy development. Outcomes in human clinical trials are compared and contrasted with the result of the preclinical dog trials. PMID:25671556

  3. Problem of technological inheritance in machine engineering

    NASA Astrophysics Data System (ADS)

    Blumenstein, Valery; Rakhimyanov, Kharis; Heifetz, Mikhail; Kleptzov, Alexander

    2016-01-01

    This article demonstrates the importance of the research study with regard to the technological inheritance of the properties, which characterize the surface layer, at different stages of a part's life cycle. It looks back at the major achievements and gives the findings relating to the technological inheritance of the parameters of the surface layer strength and quality as well as to how they affect the performance properties of machine parts. It demonstrates that high rates of machine engineering development, occurrence of new materials and more complicated machine operation environment require a shorter period for design-to-manufacture facility by reducing experiments and increasing design work. That, in its turn, generates the necessity in more complex but also more accurate models of metal behavior under stressing. It is especially critical for strengthening treatment. Among them are the models developed within the mechanics of technological inheritance. It is assumed that at the stages of a part's life cycle deformation accumulates on a continuous basis and the plasticity reserve of the metal, which the surface layer is made of, depletes. The research study of technological inheritance and the discovery of physical patterns of the evolution and degradation of the structures in a thin surface layer, which occur during machining and operational stressing of parts made from existing and unique including nanopatterned metals, is a crucial scientific challenge. This leads to the acquisition of new knowledge in the plasticity of state-of-the-art metals in the conditions of complex non monotonous stressing and to the development of efficient integrated and combined methods of technological impact.

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

    MedlinePlus

    ... with neuromyotonia is a rare form of inherited peripheral neuropathy. This group of conditions affects an estimated 1 ... Page National Institute of Neurological Disorders and Stroke: Peripheral Neuropathy Fact Sheet Educational Resources (2 links) Merck Manual ...

  5. Paternal inheritance in mealybugs (Hemiptera: Coccoidea: Pseudococcidae).

    PubMed

    Kol-Maimon, Hofit; Mendel, Zvi; Franco, José Carlos; Ghanim, Murad

    2014-10-01

    Mealybugs have a haplodiploid reproduction system, with paternal genome elimination (PGE); the males are diploid soon after fertilization, but during embryogenesis, the male paternal set of chromosomes becomes heterochromatic (HC) and therefore inactive. Previous studies have suggested that paternal genes can be passed on from mealybug males to their sons, but not necessarily by any son, to the next generation. We employed crosses between two mealybug species--Planococcus ficus (Signoret) and Planococcus citri (Risso)--and between two populations of P. ficus, which differ in their mode of pheromone attraction, in order to demonstrate paternal inheritance from males to F2 through F1 male hybrids. Two traits were monitored through three generations: mode of male pheromone attraction (pherotype) and sequences of the internal transcribed spacer 2 (ITS2) gene segment (genotype). Our results demonstrate that paternal inheritance in mealybugs can occur from males to their F2 offspring, through F1 males (paternal line). F2 backcrossed hybrid males expressed paternal pherotypes and ITS2 genotypes although their mother originated through a maternal population. Further results revealed other, hitherto unknown, aspects of inheritance in mealybugs, such as that hybridization between the two species caused absence of paternal traits in F2 hybrid females produced by F1 hybrid females. Furthermore, hybridization between the two species raised the question of whether unattracted males have any role in the interactions between P. ficus and P. citri.

  6. Phenotype as Agent for Epigenetic Inheritance

    PubMed Central

    Torday, John S.; Miller, William B.

    2016-01-01

    The conventional understanding of phenotype is as a derivative of descent with modification through Darwinian random mutation and natural selection. Recent research has revealed Lamarckian inheritance as a major transgenerational mechanism for environmental action on genomes whose extent is determined, in significant part, by germ line cells during meiosis and subsequent stages of embryological development. In consequence, the role of phenotype can productively be reconsidered. The possibility that phenotype is directed towards the effective acquisition of epigenetic marks in consistent reciprocation with the environment during the life cycle of an organism is explored. It is proposed that phenotype is an active agent in niche construction for the active acquisition of epigenetic marks as a dominant evolutionary mechanism rather than a consequence of Darwinian selection towards reproductive success. The reproductive phase of the life cycle can then be appraised as a robust framework in which epigenetic inheritance is entrained to affect growth and development in continued reciprocal responsiveness to environmental stresses. Furthermore, as first principles of physiology determine the limits of epigenetic inheritance, a coherent justification can thereby be provided for the obligate return of all multicellular eukaryotes to the unicellular state. PMID:27399791

  7. Paternal inheritance in mealybugs (Hemiptera: Coccoidea: Pseudococcidae)

    NASA Astrophysics Data System (ADS)

    Kol-Maimon, Hofit; Mendel, Zvi; Franco, José Carlos; Ghanim, Murad

    2014-10-01

    Mealybugs have a haplodiploid reproduction system, with paternal genome elimination (PGE); the males are diploid soon after fertilization, but during embryogenesis, the male paternal set of chromosomes becomes heterochromatic (HC) and therefore inactive. Previous studies have suggested that paternal genes can be passed on from mealybug males to their sons, but not necessarily by any son, to the next generation. We employed crosses between two mealybug species— Planococcus ficus (Signoret) and Planococcus citri (Risso)—and between two populations of P. ficus, which differ in their mode of pheromone attraction, in order to demonstrate paternal inheritance from males to F2 through F1 male hybrids. Two traits were monitored through three generations: mode of male pheromone attraction (pherotype) and sequences of the internal transcribed spacer 2 (ITS2) gene segment (genotype). Our results demonstrate that paternal inheritance in mealybugs can occur from males to their F2 offspring, through F1 males (paternal line). F2 backcrossed hybrid males expressed paternal pherotypes and ITS2 genotypes although their mother originated through a maternal population. Further results revealed other, hitherto unknown, aspects of inheritance in mealybugs, such as that hybridization between the two species caused absence of paternal traits in F2 hybrid females produced by F1 hybrid females. Furthermore, hybridization between the two species raised the question of whether unattracted males have any role in the interactions between P. ficus and P. citri.

  8. Mitochondrial inheritance in a mitochondrially mediated disease.

    PubMed

    Egger, J; Wilson, J

    1983-07-21

    Mendelian inheritance involves the transmission to successive generations of DNA contained in genes in the nucleus, but DNA is also contained in mitochondria, where it is believed to be responsible for the encoding of certain mitochondrial enzymes. Since nearly all mitochondrial DNA is maternally transmitted, one might expect a nonmendelian pattern of inheritance in mitochondrial cytopathy, a syndrome in which there are abnormalities in mitochondrial structure and deficiencies in a variety of mitochondrial enzymes. We studied the pedigrees of 6 affected families whose members we had examined personally and of 24 families described in the literature. In 27 families, exclusively maternal transmission occurred; in 3 there was also paternal transmission in one generation. Altogether, 51 mothers but only 3 fathers had transmitted the condition. These results are consistent with mitochondrial transmission of mitochondrial cytopathy; the inheritance and enzyme defects of mitochondrial cytopathy can be considered in the light of recent evidence that subunits of respiratory-enzyme complexes are encoded solely by mitochondrial DNA. The occasional paternal transmission may be explained if certain enzyme subunits that are encoded by nuclear DNA are affected.

  9. Qualitative analysis of dermatoglyphics of the digito-palmar complex in children with severe recessive perceptively impaired hearing.

    PubMed

    Sikić, Nada; Milicić, Jasna; Vrca, Andelko; Dulcić, Adinda; Runjić, Nada

    2009-06-01

    The possible hereditary indicated differences in the ascending family tree was investigated in children with severe recessive perceptively impaired hearing, their parents, and healthy controls, using qualitative analysis of dermatoglyphics of the digito-palmar complex. The chi2 test was performed and biological distance was investigated by means according to Hiernaux Ag methods, and presented using Ward's method for the examined groups. The results show that the healthy control group differs from the groups of boys and girls with impaired hearing and also from their fathers mostly in palmar variables. The mothers were biologically more distant from the examined groups of patients, and more similar to the control group of randomly selected healthy female controls. The results indicate polygenic inheritance of sporadic sensoneurial hearing loss.

  10. The Great Recession, somatic symptomatology and alcohol use and abuse.

    PubMed

    Vijayasiri, Ganga; Richman, Judith A; Rospenda, Kathleen M

    2012-09-01

    While most research has examined the long-term effects of alcohol consumption on health, the current study examines how health status impacts on drinking behavior. Using data from a national study conducted between 2010 and 2011 to assess the impact of the recession on drinking behavior, this study examines how economic hardships linked to the recent economic recession affect physical health, and how physical health may in turn affect alcohol use. Structural equation models were used to test the predicted associations. The data demonstrate that many of the economic stressors linked to the recession are associated with increased somatic symptoms. Somatic symptoms are also associated with increased drinking for men, but not for women. These findings suggest that men may use alcohol to self medicate somatic symptomatology. The current findings are consistent with gender role-based explanations that account for gender disparities in the utilization of medical care.

  11. The Great Recession and the risk for child maltreatment.

    PubMed

    Brooks-Gunn, Jeanne; Schneider, William; Waldfogel, Jane

    2013-10-01

    This study draws on the Fragile Families and Child Wellbeing Study (N=2,032), a birth cohort study of families with children from 20 U.S. cities. Interviews occurred between August 2007, and February 2010, when the children were approximately 9 years old. Macro-economic indicators of the Great Recession such as the Consumer Sentiment Index and unemployment and home foreclosure rates were matched to the data to estimate the links between different measures of the Great Recession and high frequency maternal spanking. We find that the large decline in consumer confidence during the Great Recession, as measured by the Consumer Sentiment Index, was associated with worse parenting behavior. In particular, lower levels of consumer confidence were associated with increased levels of high frequency spanking, a parenting behavior that is associated with greater likelihood of being contacted by child protective services.

  12. The Great Recession and the Risk for Child Maltreatment

    PubMed Central

    Brooks-Gunn, Jeanne; Schneider, William; Waldfogel, Jane

    2013-01-01

    This study draws on the Fragile Families and Child Wellbeing Study (N = 2,032), a birth cohort study of families with children from 20 U.S. cities. Interviews occurred between August 2007, and February 2010, when the children were approximately 9 years old. Macro-economic indicators of the Great Recession such as the Consumer Sentiment Index and unemployment and home foreclosure rates were matched to the data to estimate the links between different measures of the Great Recession and high frequency maternal spanking. We find that the large decline in consumer confidence during the Great Recession, as measured by the Consumer Sentiment Index, was associated with worse parenting behavior. In particular, lower levels of consumer confidence were associated with increased levels of high frequency spanking, a parenting behavior that is associated with greater likelihood of being contacted by child protective services. PMID:24045057

  13. The Great Recession, Somatic Symptomatology and Alcohol Use and Abuse

    PubMed Central

    Vijayasiri, Ganga; Richman, Judith A.; Rospenda, Kathleen M.

    2012-01-01

    While most research has examined the long-term effects of alcohol consumption on health, the current study examines how health status impacts on drinking behavior. Using data from a national study conducted between 2010 and 2011 to assess the impact of the recession on drinking behavior, this study examines how economic hardships linked to the recent economic recession affect physical health, and how physical health may in turn affect alcohol use. Structural equation models were used to test the predicted associations. The data demonstrate that many of the economic stressors linked to the recession are associated with increased somatic symptoms. Somatic symptoms are also associated with increased drinking for men, but not for women. These findings suggest that men may use alcohol to self medicate somatic symptomatology. The current findings are consistent with gender role-based explanations that account for gender disparities in the utilization of medical care. PMID:22632797

  14. Maternal inheritance and mitochondrial DNA variants in familial Parkinson's disease

    PubMed Central

    2010-01-01

    Background Mitochondrial function is impaired in Parkinson's disease (PD) and may contribute to the pathogenesis of PD, but the causes of mitochondrial impairment in PD are unknown. Mitochondrial dysfunction is recapitulated in cell lines expressing mitochondrial DNA (mtDNA) from PD patients, implicating mtDNA variants or mutations, though the role of mtDNA variants or mutations in PD risk remains unclear. We investigated the potential contribution of mtDNA variants or mutations to the risk of PD. Methods We examined the possibility of a maternal inheritance bias as well as the association between mitochondrial haplogroups and maternal inheritance and disease risk in a case-control study of 168 multiplex PD families in which the proband and one parent were diagnosed with PD. 2-tailed Fisher Exact Tests and McNemar's tests were used to compare allele frequencies, and a t-test to compare ages of onset. Results The frequency of affected mothers of the proband with PD (83/167, 49.4%) was not significantly different from the frequency of affected females of the proband generation (115/259, 44.4%) (Odds Ratio 1.22; 95%CI 0.83 - 1.81). After correcting for multiple tests, there were no significant differences in the frequencies of mitochondrial haplogroups or of the 10398G complex I gene polymorphism in PD patients compared to controls, and no significant associations with age of onset of PD. Mitochondrial haplogroup and 10398G polymorphism frequencies were similar in probands having an affected father as compared to probands having an affected mother. Conclusions These data fail to demonstrate a bias towards maternal inheritance in familial PD. Consistent with this, we find no association of common haplogroup-defining mtDNA variants or for the 10398G variant with the risk of PD. However, these data do not exclude a role for mtDNA variants in other populations, and it remains possible that other inherited mitochondrial DNA variants, or somatic mDNA mutations, contribute

  15. A new autosomal recessive spastic ataxia associated with frequent white matter changes maps to 2q33-34.

    PubMed

    Thiffault, I; Rioux, M F; Tetreault, M; Jarry, J; Loiselle, L; Poirier, J; Gros-Louis, F; Mathieu, J; Vanasse, M; Rouleau, G A; Bouchard, J P; Lesage, J; Brais, B

    2006-09-01

    Recessive ataxias are a heterogeneous group of diseases. We identified a group of 23 French-Canadian cases belonging to 17 families affected by an autosomal recessive spastic ataxia associated with frequent white matter changes. The fact that 59% of these families have a genealogical relationship to the Portneuf County of Quebec suggests that this is a new form of ataxia with a regional founder effect. All cases present with cerebellar ataxia and spasticity. There is great intrafamilial and interfamilial variability, as illustrated by the spectrum of age of diagnosis (range: 2-59 years, mean: 15.0) and the presence of white matter changes on MRI in 52.4% of cases. The more severe cases have spasticity from birth, scoliosis, dystonia and cognitive impairment and were considered cases of cerebral palsy. Brain MRI constantly shows cerebellar atrophy, which in some cases may be associated with cortical atrophy, leucoencephalopathy and corpus callosum thinning. A genome wide scan uncovered linkage of three families to marker D2S2321 localized on chromosome 2q33-34. Linkage analysis confirmed that all families are linked to the same region [multipoint log of the odds (LOD) score of 5.95]. Haplotype analysis and allele sharing suggest that one common mutation may account for 97% of carrier chromosomes in Quebec. The uncovering of the mutated gene may point to a common pathway for pyramidal and cerebellar degeneration as both are often observed in recessive ataxias and complicated paraplegias.

  16. Inheritance and characterization of strong resistance to phosphine in Sitophilus oryzae (L.).

    PubMed

    Nguyen, Tam T; Collins, Patrick J; Ebert, Paul R

    2015-01-01

    Sitophilus oryzae (Linnaeus) is a major pest of stored grain across Southeast Asia and is of increasing concern in other regions due to the advent of strong resistance to phosphine, the fumigant used to protect stored grain from pest insects. We investigated the inheritance of genes controlling resistance to phosphine in a strongly resistant S. oryzae strain (NNSO7525) collected in Australia and find that the trait is autosomally inherited and incompletely recessive with a degree of dominance of -0.66. The strongly resistant strain has an LC50 52 times greater than a susceptible reference strain (LS2) and 9 times greater than a weakly resistant strain (QSO335). Analysis of F2 and backcross progeny indicates that two or more genes are responsible for strong resistance, and that one of these genes, designated So_rph1, not only contributes to strong resistance, but is also responsible for the weak resistance phenotype of strain QSO335. These results demonstrate that the genetic mechanism of phosphine resistance in S. oryzae is similar to that of other stored product insect pests. A unique observation is that a subset of the progeny of an F1 backcross generation are more strongly resistant to phosphine than the parental strongly resistant strain, which may be caused by multiple alleles of one of the resistance genes.

  17. Advancing our understanding of the inheritance and transmission of pectus excavatum.

    PubMed

    Horth, Lisa; Stacey, Michael W; Proud, Virginia K; Segna, Kara; Rutherford, Chelsea; Nuss, Donald; Kelly, Robert E

    2012-09-01

    Pectus excavatum is the most common congenital chest wall abnormality expressed in children, yet its inheritance is poorly understood. Here we present the first comprehensive assessment of the inheritance of this disorder. After evaluating 48 pedigrees and 56 clinical traits of probands and family members, we find strong evidence of autosomal recessive, genetic control for this disorder. Additionally there is likely more than one pectus disease-associated allele, as well as a relatively large number of disease allele carriers in the human population. Some clinical traits appear important and may serve as reliable indicators for predicting the likelihood of pectus excavatum in children before severe symptoms present. Quantifying sex-ratio bias in probands demonstrates a highly significant male bias associated with pectus excavatum. When combined with pedigree data, sex-bias is indicative of sex-linked, sex-limited, and/or epigenetic control such as X-inactivation, reiterating a point made with pedigrees alone, which is that more than one mutation is likely responsible for this disorder.

  18. Prevalence of inherited ichthyosis in France: a study using capture-recapture method

    PubMed Central

    2014-01-01

    Background Inherited ichthyoses represent a group of rare skin disorders characterized by scaling, hyperkeratosis and inconstant erythema, involving most of the tegument. Epidemiology remains poorly described. This study aims to evaluate the prevalence of inherited ichthyosis (excluding very mild forms) and its different clinical forms in France. Methods Capture – recapture method was used for this study. According to statistical requirements, 3 different lists (reference/competence centres, French association of patients with ichthyosis and internet network) were used to record such patients. The study was conducted in 5 areas during a closed period. Results The prevalence was estimated at 13.3 per million people (/M) (CI95%, [10.9 – 17.6]). With regard to autosomal recessive congenital ichthyosis, the prevalence was estimated at 7/M (CI 95% [5.7 – 9.2]), with a prevalence of lamellar ichthyosis and congenital ichthyosiform erythroderma of 4.5/M (CI 95% [3.7 – 5.9]) and 1.9/M (CI 95% [1.6 – 2.6]), respectively. Prevalence of keratinopathic forms was estimated at 1.1/M (CI 95% [0.9 – 1.5]). Prevalence of syndromic forms (all clinical forms together) was estimated at 1.9/M (CI 95% [1.6 – 2.6]). Conclusions Our results constitute a crucial basis to properly size the necessary health measures that are required to improve patient care and design further clinical studies. PMID:24393603

  19. OPTN 691_692insAG is a founder mutation causing recessive ALS and increased risk in heterozygotes

    PubMed Central

    Goldstein, Orly; Nayshool, Omri; Nefussy, Beatrice; Traynor, Bryan J.; Renton, Alan E.; Gana-Weisz, Mali; Drory, Vivian E.

    2016-01-01

    Objective: To detect genetic variants underlying familial and sporadic amyotrophic lateral sclerosis (ALS). Methods: We analyzed 2 founder Jewish populations of Moroccan and Ashkenazi origins and ethnic matched controls. Exome sequencing of 2 sisters with ALS from Morocco was followed by genotyping the identified causative null mutation in 379 unrelated patients with ALS and 1,000 controls. The shared risk haplotype was characterized using whole-genome single nucleotide polymorphism array. Results: We identified 5 unrelated patients with ALS homozygous for the null 691_692insAG mutation in the optineurin gene (OPTN), accounting for 5.8% of ALS of Moroccan origin and 0.3% of Ashkenazi. We also identified a high frequency of heterozygous carriers among patients with ALS, 8.7% and 2.9%, respectively, compared to 0.75% and 1.0% in controls. The risk of carriers for ALS was significantly increased, with odds ratio of 13.46 and 2.97 in Moroccan and Ashkenazi Jews, respectively. We determined that 691_692insAG is a founder mutation in the tested populations with a minimal risk haplotype of 58.5 Kb, encompassing the entire OPTN gene. Conclusions: Our data show that OPTN 691_692insAG mutation is a founder mutation in Moroccan and Ashkenazi Jews. This mutation causes autosomal recessive ALS and significantly increases the risk to develop the disease in heterozygous carriers, suggesting both a recessive mode of inheritance and a dominant with incomplete penetrance. These data emphasize the important role of OPTN in ALS pathogenesis, and demonstrate the complex genetics of ALS, as the same mutation leads to different phenotypes and appears in 2 patterns of inheritance. PMID:26740678

  20. The fate of 12 recessive mutations in a single village.

    PubMed

    Zlotogora, J; Hujerat, Y; Barges, S; Shalev, S A; Chakravarti, A

    2007-03-01

    In a Muslim Arab village, relatively isolated because of the preference of consanguineous marriages, we studied the fate of 12 mutations in 5 different genes. The study was based on carriers detected among relatives of affected patients and of carriers discovered in a random sample of 424 adults. Most of the mutations have been introduced by a carrier(s) originating from another village, but a few have been de novo events. Mutations that are very frequent in the entire village were introduced soon after the foundation of the village. Examples of such mutations are [GBJ2, 35Gdel] and [MEFV, M680I], with a carrier frequency of 7.8% and 6.2%, respectively. Many of the other mutations that are rare were introduced recently into the village and are frequent only among the descendants of the first couple carrying the mutation. For instance all the carriers of [ARSA, Q190H], responsible for metachromatic leukodystrophy, were found among the 218 descendants of a couple who were living in the village 4 generations ago. Since the village is typical for the region this study allows for some general conclusions to be drawn. In a population with a high degree of inbreeding the diagnosis of a single family with a patient(s) affected with a recessive disorder points to a recent event, while the finding of a rare disease in several families from an inbred population points to an older mutation. Mutations are often "exported" from one population to another by marriage. In the new inbred population this novel mutation will either be lost or will become frequent as the result of a founder effect. These observations are important for genetic counselling in the case of a recent mutation, since only the descendants of the founder couple are at risk, while in the case of older mutations the risk may be for the entire village. In the case of those frequent ancient mutations, the risk for a relative of an affected individual will be similar whether he marries a close relative or any random