Search results for "Intellectual Disability"
showing 10 items of 303 documents
Delineation of a new chromosome 20q11.2 duplication syndrome including the ASXL1 gene.
2013
We report on three males with de novo overlapping 7.5, 9.8, and 10 Mb duplication of chromosome 20q11.2. Together with another patient previously published in the literature with overlapping 20q11 microduplication, we show that such patients display common clinical features including metopic ridging/trigonocephaly, developmental delay, epicanthal folds, and short hands. The duplication comprised the ASXL1 gene, in which de novo heterozygous nonsense or truncating mutations have recently been reported in patients with Borhing-Opitz syndrome. Because of craniofacial features in common with Borhing-Opitz syndrome, in particular metopic ridging/trigonocephaly, we suggest that duplication of ASX…
Variable phenotype in 17q12 microdeletions: Clinical and molecular characterization of a new case
2014
Microdeletions of 17q12 including the hepatocyte nuclear factor 1 beta (HNF1B) gene, as well as point mutations of this gene, are associated with the Renal Cysts and Diabetes syndrome (RCAD, OMIM 137920) and genitourinary alterations. Also, microdeletions encompassing HNF1B were identified as a cause of Mayer-Rokitansky-Kuster-Hauser Syndrome (MRKH, OMIM 277000) in females and, recently, were associated with intellectual disability, autistic features, cerebral anomaly and facial dysmorphisms. In this report, we describe a boy with a deletion in 17q12 region detected by SNP array, encompassing the HNF1B gene, that showed dysmorphic features, intellectual disability (ID), serious speech delay…
Widening of the genetic and clinical spectrum of Lamb-Shaffer syndrome, a neurodevelopmental disorder due to SOX5 haploinsufficiency
2020
International audience; PURPOSE: Lamb-Shaffer syndrome (LAMSHF) is a neurodevelopmental disorder described in just over two dozen patients with heterozygous genetic alterations involving SOX5, a gene encoding a transcription factor regulating cell fate and differentiation in neurogenesis and other discrete developmental processes. The genetic alterations described so far are mainly microdeletions. The present study was aimed at increasing our understanding of LAMSHF, its clinical and genetic spectrum, and the pathophysiological mechanisms involved.METHODS: Clinical and genetic data were collected through GeneMatcher and clinical or genetic networks for 41 novel patients harboring various ty…
EPHA7 haploinsufficiency is associated with a neurodevelopmental disorder
2021
International audience; Ephrin receptor and their ligands, the ephrins, are widely expressed in the developing brain. They are implicated in several developmental processes that are crucial for brain development. Deletions in genes encoding for members of the Eph/ephrin receptor family were reported in several neurodevelopmental disorders. The ephrin receptor A7 gene (EPHA7) encodes a member of ephrin receptor subfamily of the protein-tyrosine kinase family. EPHA7 plays a role in corticogenesis processes, determines brain size and shape, and is involved in development of the central nervous system. One patient only was reported so far with a de novo deletion encompassing EPHA7 in 6q16.1. We…
20 ans après: a second mutation in MAOA identified by targeted high-throughput sequencing in a family with altered behavior and cognition
2013
Intellectual disability (ID) is characterized by an extraordinary genetic heterogeneity, with >250 genes that have been implicated in monogenic forms of ID. Because this complexity precluded systematic testing for mutations and because clinical features are often non-specific, for some of these genes only few cases or families have been unambiguously documented. It is the case of the X-linked gene encoding monoamine oxidase A (MAOA), for which only one nonsense mutation has been identified in Brunner syndrome, characterized in a single family by mild non-dysmorphic ID and impulsive, violent and aggressive behaviors. We have performed targeted high-throughput sequencing of 220 genes, includi…
Elevated serum triiodothyronine and intellectual and motor disability with paroxysmal dyskinesia caused by a monocarboxylate transporter 8 gene mutat…
2008
Monocarboxylate transporter 8 (MCT8 or SLC16A2) is important for the neuronal uptake of triiodothyronine (T3) in its function as a specific and active transporter of thyroid hormones across the cell membrane, thus being essential for human brain development. We report on a German male with Allan-Herndon-Dudley syndrome presenting with severe intellectual and motor disability, paroxysmal dyskinesia combined with truncal muscular hypotonia, and peripheral muscular hypertonia at his current age of 9 years. Additionally, the patient has a lesion in the left putamen region revealed by magnetic resonance imaging and elevated serum T3 levels. The male appeared to have a hemizygous mutation (R271H)…
Is it wrong to deliberately conceive or give birth to a child with mental retardation?
2002
This paper discusses the issues of deciding to have a child with mental retardation, and of terminating a pregnancy when the future child is known to have the same disability. I discuss these problems by criticizing a utilitarian argument, namely, that one should act in a way that results in less suffering and less limited opportunity in the world. My argument is that future parents ought to assume a strong responsibility towards the well-being of their prospective children when they decide to reproduce. The moral point in cases in which our acts affect the well-being of future children should be expressed strictly in terms of parents' culpability. Future children thus do not have current m…
ZBTB20 is crucial for the specification of a subset of callosal projection neurons and astrocytes in the mammalian neocortex
2021
ABSTRACT Neocortical progenitor cells generate subtypes of excitatory projection neurons in sequential order followed by the generation of astrocytes. The transcription factor zinc finger and BTB domain-containing protein 20 (ZBTB20) has been implicated in regulation of cell specification during neocortical development. Here, we show that ZBTB20 instructs the generation of a subset of callosal projections neurons in cortical layers II/III in mouse. Conditional deletion of Zbtb20 in cortical progenitors, and to a lesser degree in differentiating neurons, leads to an increase in the number of layer IV neurons at the expense of layer II/III neurons. Astrogliogenesis is also affected in the mut…
Recurrent missense variant in the nuclear export signal of FMR1 associated with FXS-like phenotype including intellectual disability, ASD, facial abn…
2021
Fragile X syndrome (FXS; MIM 300624) is an X-linked genetic disorder characterized by physical abnormalities associated with intellectual disability and a wide spectrum of neurological and psychiatric impairments. FXS occurs more frequently in males, 1 in 5000 males and 1 in 8000 females accounting for 1-2% of overall intellectual disability (ID). In more than 99% of patients, FXS results from expansions of a CGG triplet repeat (>200 in male) of the FMR1 gene. In the last years an increasing number, albeit still limited, of FXS subjects carrying FMR1 mutations including deletions, splicing errors, missense, and nonsense variants was reported. Nevertheless, the studies concerning the func…
Clinical Significance of Rare Copy Number Variations in Epilepsy A Case-Control Survey Using Microarray-Based Comparative Genomic Hybridization
2012
Objective To perform an extensive search for genomic rearrangements by microarray-based comparative genomic hybridization in patients with epilepsy. Design Prospective cohort study. Setting Epilepsy centers in Italy. Patients Two hundred seventy-nine patients with unexplained epilepsy, 265 individuals with nonsyndromic mental retardation but no epilepsy, and 246 healthy control subjects were screened by microarray-based comparative genomic hybridization. Main Outcomes Measures Identification of copy number variations (CNVs) and gene enrichment. Results Rare CNVs occurred in 26 patients (9.3%) and 16 healthy control subjects (6.5%) (P = .26). The CNVs identified in patients were larger (P = …