Search results for "Microcephaly"
showing 10 items of 70 documents
Galloway-Mowat syndrome: New insights from bioinformatics and expression during Xenopus embryogenesis.
2021
Abstract Galloway-Mowat syndrome (GAMOS) is a rare developmental disease. Patients suffer from congenital brain anomalies combined with renal abnormalities often resulting in an early-onset steroid-resistant nephrotic syndrome. The etiology of GAMOS has a heterogeneous genetic contribution. Mutations in more than 10 different genes have been reported in GAMOS patients. Among these are mutations in four genes encoding members of the human KEOPS ( k inase, e ndopeptidase and o ther p roteins of small s ize) complex, including OSGEP, TP53RK, TPRKB and LAGE3. Until now, these components have been functionally mainly investigated in bacteria, eukarya and archaea and in humans in the context of t…
Homozygous Truncating Intragenic Duplication in TUSC3 Responsible for Rare Autosomal Recessive Nonsyndromic Intellectual Disability with No Clinical …
2014
Intellectual disability (ID), which affects around 2–3% of the general population, is classically divided into syndromic and nonsyndromic forms, with several modes of inheritance. Nonsyndromic autosomal recessive ID (NS-ARID) appears extremely heterogeneous with numerous genes identified to date, including inborn errors of metabolism. The TUSC3 gene encodes a subunit of the endoplasmic reticulum (ER)-bound oligosaccharyltransferase complex, which mediates a key step of N-glycosylation. To date, only five families with NS-ARID and TUSC3 mutations or rearrangements have been reported in the literature. All patients had speech delay, moderate-to-severe ID, and moderate facial dysmorphism. Micr…
Cohen syndrome is associated with major glycosylation defects
2014
International audience; Cohen syndrome (CS) is a rare autosomal recessive disorder with multisytemic clinical features due to mutations in the VPS13B gene, which has recently been described encoding a mandatory membrane protein involved in Golgi integrity. As the Golgi complex is the place where glycosylation of newly synthesized proteins occurs, we hypothesized that VPS13B deficiency, responsible of Golgi apparatus disturbance, could lead to glycosylation defects and/or mysfunction of this organelle, and thus be a cause of the main clinical manifestations of CS. The glycosylation status of CS serum proteins showed a very unusual pattern of glycosylation characterized by a significant accum…
Clinical and Biochemical Features in a Patient With Mitochondrial Fission Factor Gene Alteration
2018
Mitochondrial Fission Factor (MFF) is part of a protein complex that promotes mitochondria and peroxisome fission. Hitherto, only 5 patients have been reported harboring mutations in MFF, all of them with the clinical features of a very early onset Leigh-like encephalopathy. We report on an 11-year-old boy with epileptic encephalopathy. He presented with neurological regression, epileptic myoclonic seizures, severe intellectual disability, microcephaly, tetraparesis, optic atrophy, and ophthalmoplegia. Brain MRI pattern was compatible with Leigh syndrome. NGS-based analysis of a gene panel for mitochondrial disorders revealed a homozygous c.892C>T (p. Arg298*) in the MFF gene. Fluorescen…
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…
A novel mutation of WDR62 gene associated with severe phenotype including infantile spasm, microcephaly, and intellectual disability
2017
Abstract The autosomal recessive form of primary microcephaly (MCPH) is a rare disorder characterized by head circumference of at least 3 standard deviation below the mean. The MCPH exhibits genetic heterogeneity with thirteen loci (MCPH1-MCPH13) identified, and associated with variable degree of intellectual disability. It has been reported that WDR62 is the second causative gene of autosomal recessive microcephaly (MCPH2) playing a significant role in spindle formation and the proliferation of neuronal progenitor cells. We report a clinical feature, electroclinical findings, and clinical course of a patient with a severe phenotype of MCPH2 including microcephaly, refractory infantile spas…
A new family with an SLC9A6 mutation expanding the phenotypic spectrum of Christianson syndrome
2016
Using targeted next generation sequencing, we have identified a splicing mutation (c.526-9_526-5del) in the SLC9A6 gene in a 9-year-old boy with mild intellectual disability (ID), microcephaly, and social interaction disabilities. This intronic microdeletion leads to the skipping of exon 3 and to an in-frame deletion of 26 amino acids in the TM4 domain. It segregates with cognitive impairment or learning difficulties in other members of the family. Mutations in SLC9A6 have been reported in X-linked Christianson syndrome associating severe to profound intellectual deficiency and an Angelman-like phenotype with microcephaly, absent speech, ataxia with progressive cerebellar atrophy, ophthalmo…
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…
Cerebroarthrodigital syndrome: A newly recognized formal genesis syndrome in three patients with apparent arthromyodysplasia and sacral agenesis, bra…
1980
We describe three patients with a complex syndrome of apparent arthromyodysplasia, dyscephaly, sacral agenesis, and hypoplastic digitis. Cause is unknown, but an environmental cause is suspected on the basis of ergotamine exposure in one case and diazoxide intake in another, together with suggestive similarities to anomalies seen in animals treated with these drugs and to calves with the Australian hydranencephaly/arthrogryposis syndrome caused by Akebane or Aino virus. Pathogenetically the primary defect may be a neural tube-neural crest dysplasia with multiple secondary and tertiary manifestations and deformities.
The DYRK1A gene is a cause of syndromic intellectual disability with severe microcephaly and epilepsy.
2012
Background DYRK1A plays different functions during development, with an important role in controlling brain growth through neuronal proliferation and neurogenesis. It is expressed in a gene dosage dependent manner since dyrk1a haploinsufficiency induces a reduced brain size in mice, and DYRK1A overexpression is the candidate gene for intellectual disability (ID) and microcephaly in Down syndrome. We have identified a 69 kb deletion including the 5′ region of the DYRK1A gene in a patient with growth retardation, primary microcephaly, facial dysmorphism, seizures, ataxic gait, absent speech and ID. Because four patients previously reported with intragenic DYRK1A rearrangements or 21q22 microd…