Search results for "INHERIT"
showing 10 items of 237 documents
Heterozygous HMGB1 loss-of-function variants are associated with developmental delay and microcephaly
2021
International audience; 13q12.3 microdeletion syndrome is a rare cause of syndromic intellectual disability. Identification and genetic characterization of patients with 13q12.3 microdeletion syndrome continues to expand the phenotypic spectrum associated with it. Previous studies identified four genes within the approximately 300 Kb minimal critical region including two candidate protein coding genes: KATNAL1 and HMGB1. To date, no patients carrying a sequence-level variant or a single gene deletion in HMGB1 or KATNAL1 have been described. Here we report six patients with loss-of-function variants involving HMGB1 and who had phenotypic features similar to the previously described 13q12.3 m…
Inheritance patterns of ATCCT repeat interruptions in spinocerebellar ataxia type 10 (SCA10) expansions
2017
Spinocerebellar ataxia type 10 (SCA10), an autosomal dominant cerebellar ataxia disorder, is caused by a non-coding ATTCT microsatellite repeat expansion in the ataxin 10 gene. In a subset of SCA10 families, the 5'-end of the repeat expansion contains a complex sequence of penta- and heptanucleotide interruption motifs which is followed by a pure tract of tandem ATCCT repeats of unknown length at its 3'-end. Intriguingly, expansions that carry these interruption motifs correlate with an epileptic seizure phenotype and are unstable despite the theory that interruptions are expected to stabilize expanded repeats. To examine the apparent contradiction of unstable, interruption-positive SCA10 e…
Incorporating Functional Genomic Information to Enhance Polygenic Signal and Identify Variants Involved in Gene-by-Environment Interaction for Young …
2018
BACKGROUND: Characterizing aggregate genetic risk for alcohol misuse and identifying variants involved in gene-by-environment (G × E) interaction effects has so far been a major challenge. We hypothesized that functional genomic information could be used to enhance detection of polygenic signal underlying alcohol misuse and to prioritize identification of single nucleotide polymorphisms (SNPs) most likely to exhibit G × E effects.METHODS: We examined these questions in the young adult FinnTwin12 sample (n = 1,170). We used genomewide association estimates from an independent sample to derive 2 types of polygenic scores for alcohol problems in FinnTwin12. Genomewide polygenic scores included…
Shared genetic etiology between alcohol dependence and major depressive disorder
2018
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A de novo microdeletion of SEMA5A in a boy with autism spectrum disorder and intellectual disability.
2016
AbstractSemaphorins are a large family of secreted and membrane-associated proteins necessary for wiring of the brain. Semaphorin 5A (SEMA5A) acts as a bifunctional guidance cue, exerting both attractive and inhibitory effects on developing axons. Previous studies have suggested that SEMA5A could be a susceptibility gene for autism spectrum disorders (ASDs). We first identified a de novo translocation t(5;22)(p15.3;q11.21) in a patient with ASD and intellectual disability (ID). At the translocation breakpoint on chromosome 5, we observed a 861-kb deletion encompassing the end of the SEMA5A gene. We delineated the breakpoint by NGS and observed that no gene was disrupted on chromosome 22. We…
Inbreeding removes sex differences in lifespan in a population of Drosophila melanogaster
2016
Sex differences in ageing rates and lifespan are common in nature, and an enduring puzzle for evolutionary biology. One possibility is that sex-specific mortality rates may result from recessive deleterious alleles in ‘unguarded’ heterogametic X or Z sex chromosomes (the unguarded X hypothesis). Empirical evidence for this is, however, limited. Here, we test a fundamental prediction of the unguarded X hypothesis in Drosophila melanogaster, namely that inbreeding shortens lifespan more in females (the homogametic sex in Drosophila) than in males. To test for additional sex-specific social effects, we studied the lifespan of males and females kept in isolation, in related same-sex groups, and…
Dopamine and serotonin transporter genotypes moderate sensitivity to maternal expressed emotion: the case of conduct and emotional problems in attent…
2009
Contains fulltext : 80906.pdf (Publisher’s version ) (Closed access) BACKGROUND: Mothers' positive emotions expressed about their children with attention deficit/hyperactivity disorder (ADHD) are associated with a reduced likelihood of comorbid conduct problems (CP). We examined whether this association with CP, and one with emotional problems (EMO), is moderated by variants within three genes, previously reported to be associated with ADHD and to moderate the impact of environmental risks on conduct and/or emotional problems; the dopamine transporter gene (SLC6A3/DAT1), the dopamine D4 receptor gene (DRD4) and the serotonin transporter gene (SLC6A4/5HTT). METHODS: Seven hundred and twenty-…
Linkage to chromosome 1p36 for attention-deficit/hyperactivity disorder traits in school and home settings.
2008
Contains fulltext : 69485.pdf (Publisher’s version ) (Closed access) BACKGROUND: Limited success has been achieved through previous attention-deficit/hyperactivity disorder (ADHD) linkage scans, which were all designed to map genes underlying the dichotomous phenotype. The International Multi-centre ADHD Genetics (IMAGE) project performed a whole genome linkage scan specifically designed to map ADHD quantitative trait loci (QTL). METHODS: A set of 1094 single selected Caucasian ADHD nuclear families was genotyped on a highly accurate and informative single nucleotide polymorphism (SNP) panel. Two quantitative traits measuring the children's symptoms in home and school settings were collecte…
Twelve Variants Polygenic Score for Low-Density Lipoprotein Cholesterol Distribution in a Large Cohort of Patients With Clinically Diagnosed Familial…
2022
: Background A significant proportion of individuals clinically diagnosed with familial hypercholesterolemia (FH), but without any disease-causing mutation, are likely to have polygenic hypercholesterolemia. We evaluated the distribution of a polygenic risk score, consisting of 12 low-density lipoprotein cholesterol (LDL-C)-raising variants (polygenic LDL-C risk score), in subjects with a clinical diagnosis of FH. Methods and Results Within the Lipid Transport Disorders Italian Genetic Network (LIPIGEN) study, 875 patients who were FH-mutation positive (women, 54.75%; mean age, 42.47±15.00 years) and 644 patients who were FH-mutation negative (women, 54.21%; mean age, 49.73±13.54 years) wer…
Loss-of-function maternal-effect mutations of PADI6 are associated with familial and sporadic Beckwith-Wiedemann syndrome with multi-locus imprinting…
2020
Abstract Background PADI6 is a component of the subcortical maternal complex, a group of proteins that is abundantly expressed in the oocyte cytoplasm, but is required for the correct development of early embryo. Maternal-effect variants of the subcortical maternal complex proteins are associated with heterogeneous diseases, including female infertility, hydatidiform mole, and imprinting disorders with multi-locus imprinting disturbance. While the involvement of PADI6 in infertility is well demonstrated, its role in imprinting disorders is less well established. Results We have identified by whole-exome sequencing analysis four cases of Beckwith-Wiedemann syndrome with multi-locus imprintin…