Search results for "Intellect"
showing 10 items of 642 documents
Amelioration of the abnormal phenotype of a new L1 syndrome mouse mutation with L1 mimetics
2021
L1 syndrome is a rare developmental disorder characterized by hydrocephalus of varying severity, intellectual deficits, spasticity of the legs, and adducted thumbs. Therapy is limited to symptomatic relief. Numerous gene mutations in the L1 cell adhesion molecule (L1CAM, hereafter abbreviated L1) were identified in L1 syndrome patients, and those affecting the extracellular domain of this transmembrane type 1 glycoprotein show the most severe phenotypes. Previously analyzed rodent models of the L1 syndrome focused on L1-deficient animals or mouse mutants with abrogated cell surface expression of L1, making it difficult to test L1 function-triggering mimetic compounds with potential therapeu…
NFIB Haploinsufficiency Is Associated with Intellectual Disability and Macrocephaly
2018
The nuclear factor I (NFI) family of transcription factors play an important role in normal development of multiple organs. Three NFI family members are highly expressed in the brain, and deletions or sequence variants in two of these, NFIA and NFIX, have been associated with intellectual disability (ID) and brain malformations. NFIB, however, has not previously been implicated in human disease. Here, we present a cohort of 18 individuals with mild ID and behavioral issues who are haploinsufficient for NFIB. Ten individuals harbored overlapping microdeletions of the chromosomal 9p23-p22.2 region, ranging in size from 225 kb to 4.3 Mb. Five additional subjects had point sequence variations c…
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…
Bainbridge-Ropers syndrome caused by loss-of-function variants in ASXL3: a recognizable condition
2016
International audience; Truncating ASXL3 mutations were first identified in 2013 by Bainbridge et al. as a cause of syndromic intellectual disability in four children with similar phenotypes using whole-exome sequencing. The clinical features - postulated by Bainbridge et al. to be overlapping with Bohring-Opitz syndrome - were developmental delay, severe feeding difficulties, failure to thrive and neurological abnormalities. This condition was included in OMIM as 'Bainbridge-Ropers syndrome' (BRPS, #615485). To date, a total of nine individuals with BRPS have been published in the literature in four reports (Bainbridge et al., Dinwiddie et al, Srivastava et al. and Hori et al.). In this re…
Intragenic FMR1 disease-causing variants: a significant mutational mechanism leading to Fragile-X syndrome
2017
International audience; Fragile-X syndrome (FXS) is a frequent genetic form of intellectual disability (ID). The main recurrent mutagenic mechanism causing FXS is the expansion of a CGG repeat sequence in the 5'-UTR of the FMR1 gene, therefore, routinely tested in ID patients. We report here three FMR1 intragenic pathogenic variants not affecting this sequence, identified using high-throughput sequencing (HTS): a previously reported hemizygous deletion encompassing the last exon of FMR1, too small to be detected by array-CGH and inducing decreased expression of a truncated form of FMRP protein, in three brothers with ID (family 1) and two splice variants in boys with sporadic ID: a de novo …
Associations between cognitive performance and the rehabilitation, medical care and social support provided to French children with Prader-Willi synd…
2020
International audience; Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental disorder with a characteristic behavioural phenotype. A multidisciplinary approach to care is required to prevent multiple medical complications in individuals affected by PWS. The aim of this study was to describe the rehabilitation, medical care, educational and social support provided to school-aged French PWS patients with varying neuropsychological profiles. Data were obtained from a French multicentre study that included patients aged 4-20 years with diverse genetic syndromes. Nineteen PWS subjects with a mean age of 9.2 years were included. The mean full-scale intellectual quotient (IQ) was 58 (W…
Development and psychometric properties of an instrument for the Assessment of Sexual Behaviour and Knowledge of people with Intellectual Disability
2020
Background This paper presents psychometric properties of an instrument for the Assessment of Sexual Behaviour and Knowledge of people with Intellectual Disability (ASBKID), other‐reported by professionals who are in daily contact with them. Methods and procedures Assessments of 236 individuals with intellectual disability were obtained from 100 professionals. Results Confirmatory factor analysis revealed a four‐factor structure: concern about the user's inappropriate or uninhibited sexual behaviour; perception of the user's knowledge about privacy and social norms; perception of the user's knowledge about sexuality; and concerns about the user's sexuality. A multi‐group CFA was also conduc…
Participation in collaborative projects as a precursor of trust in organizations for individuals with intellectual disability
2020
The present study focuses on organizations delivering services to individuals with intellectual disability, where trust relations between professionals and family members are required. More specifically, we examine the existence of significant differences in the degree to which family members and professionals trust each other. We also propose that their joint participation in collaborative teams (VI) will improve trust (VD). Specifically, our teams (experimental condition) designed and implemented collaborative projects with the participation of professionals and family members. Participants in the control condition did not participate in the collaborative projects. Our results confirmed t…
Estimating sexual knowledge of people with mild intellectual disability through a valid and reliable assessment scale: The ISK-ID
2021
Background Despite the relevance of assessing sexual knowledge in people with Intellectual Disability, there is a lack of appropriate assessment tools to measure this domain. The current study tests the psychometric properties of the new ‘Inventory of Sexual Knowledge of people with Intellectual Disability’ (ISK-ID). Method 345 individuals with mild intellectual disability completed the ISK-ID before and after the implementation of a sexual education program. Psychometric properties of the ISK-ID were analysed according to Multidimensional Item Response Theory (MIRT). Results Its underlying factorial structure, along with parameters derived from the MIRT (item discrimination, difficulty, an…
Novel KIF7 mutations extend the phenotypic spectrum of acrocallosal syndrome.
2012
Background Acrocallosal syndrome (ACLS) is a rare recessive disorder characterised by corpus callosum agenesis or hypoplasia, craniofacial dysmorphism, duplication of the hallux, postaxial polydactyly, and severe mental retardation. Recently, we identified mutations in KIF7, a key component of the Sonic hedgehog pathway, as being responsible for this syndrome. Methods We sequenced KIF7 in five suspected ACLS cases, one fetus and four patients, based on facial dysmorphism and brain anomalies. Results Seven mutations were identified at the KIF7 locus in these five cases, six of which are novel. We describe the first four compound heterozygous cases. In all patients, the diagnosis was suspecte…