However, mutations in MECP2 also have been identified in normal carrier female individuals, female individuals with mild learning disabilities and features of Angelman syndrome, and male individuals with Klinefelter syndrome or Rett syndrome-like features, fatal neonatal encephalopathy, and familial X-linked mental retardation with or without motor abnormalities.
Chromosome Xq28 duplications encompassing methyl-CpG-binding protein 2 gene (MECP2) are observed most in males with a severe neurodevelopmental disorder associated with hypotonia, spasticity, severe learning disability, delayed psychomotor development, and recurrent pulmonary infections.
MECP2 mutations have subsequently been identified in patients with a variety of clinical syndromes ranging from mild learning disability in females to severe mental retardation, seizures, ataxia, and sometimes neonatal encephalopathy in males.
Favorable (skewed) X inactivation can so spare a patient from the effects of mutant MECP2 that they display only the mildest learning disability or no phenotype at all.
MECP2 mutations have also been identified in individuals with a variety of clinical syndromes, including mild learning-disability in females, neonatal encephalopathy in males, and psychiatric disorders, autism and X-linked mental retardation in both males and females.
Furthermore, the panorama of phenotypes with MECP2 mutations now extends far beyond RS to include normal girls and women, mild learning disability, autistic spectrum disorders, and X-linked mental retardation.
Semi-dominant X-chromosome linked learning disability with progressive ataxia, spasticity and dystonia associated with the novel MECP2 variant p.V122A: akin to the new MECP2 duplication syndrome?
Neurofibromatosis type I (NF1) is an autosomal dominant disorder caused by mutations in the NF1 gene, leading to a variety of abnormalities in cell growth and differentiation, and to learning disabilities.
The functions of neurofibromin and VCP in spinogenesis were shown to correlate with the learning disability and dementia phenotypes seen in patients with IBMPFD.
Gross deletions of the neurofibromatosis type 1 (NF1) gene are predominantly of maternal origin and commonly associated with a learning disability, dysmorphic features and developmental delay.
The MAPT H1 haplotype has been associated with progressive supranuclear palsy, corticobasal degeneration, Parkinson's disease and Alzheimer's disease, while the H2 is linked to recurrent deletion events associated with the 17q21.31 microdeletion syndrome, a disease characterized by developmental delay and learning disability.
Array-CGH and high-throughput sequencing have dramatically expanded the number of genes implicated in isolated intellectual disabilities and LDs, highlighting the implication of neuron-specific post-mitotic transcription factors and synaptic proteins as candidate genes.
We have investigated a population consisted of 276 males with idiopathic mental retardation or learning disability and a control sample of 207 non-affected boys in order to determine if there was a possible phenotype consequence of the expanded unmethylated alleles for FRAXA/FRAXE loci.
We report the results of a five year survey of FRAXA and FRAXE mutations among boys aged 5 to 18 with special educational needs (SEN) related to learning disability.
Array CGH in patients with learning disability (mental retardation) and congenital anomalies: updated systematic review and meta-analysis of 19 studies and 13,926 subjects.
On the basis of these results, we anticipate that array-CGH will become a routine method of genome-wide screening for imbalanced rearrangements in children with learning disability.
To see whether FRAXA or FRAXE can account for the etiology of some unexplained neurodevelopmental disorders in children, we screened for trinucleotide repeat expansion in a consecutive cohort of 73 Chinese children and their mothers seen in 1995 (group 1) referred for developmental assessment due to developmental delay, language delay, attention deficit hyperactivity disorder, autistic spectrum disorder, mental retardation and/or learning disability.
Consistent with our results, (i) SCO2 deficiency and/or CCO activity defects have been reported in patients with learning disabilities including autism and (ii) mutated proteins in ASD have been found associated with p53-signaling pathways.