Ten genes (i.e., ZNF711, SRPX2, RAB40AL, MID2, ACSL4, PAK3, UBE2A, UPF3B, CUL4B, and GRIA3) in the duplication interval have been associated with mental retardation.
Here, using oligoarray-based comparative genomic hybridization (array CGH), we identified a de novo deletion of the CUL4B gene in a boy with syndromic mental retardation, minor facial anomalies, short stature, delayed puberty, hypogonadism, relative macrocephaly, gait ataxia, and pes cavus, all manifestations described previously in patients with CUL4B point mutations.
We conclude that in mentally retarded Brazilian males, non-pathogenic variants in the MECP2 gene are more common than actual pathogenic mutations, and therefore alterations in this gene have a weak relationship with mental retardation in males.
Alternatively, testing for large-scale MECP2 duplications is recommended for males presenting with mental retardation, an X-linked family history of developmental delay, and a significant proportion of previously described clinical features (particularly a history of recurrent respiratory infections).
Consistent with this notion is the recent demonstration that MECP2 mutations cause Rett syndrome (RTT, MIM 312750), a childhood neurological disorder that represents one of the most common causes of mental retardation in females.
Mutations in the X-encoded gene ATRX are known to give rise to syndromic mental retardation in male patients whereas female carriers show preferential inactivation of the mutated X chromosome and appear healthy.
Multiplex XLMR pedigrees have been reported with only one mutated patient having autism and MR: different X-located MR genes have been shown to be involved (NLGN4, MECP2, OPHN1, ZNF674 and FRAXA) which does not suggest that they could be "autism genes".
In this study we summarize the results of diagnostic testing of 30 patients with Rett syndrome (RTT) or mental retardation of unknown etiology using bidirectional sequencing of the open reading frame of the MECP2 gene.
Given that molecular investigation of XNP/ATR-X mutations is made onerous by the length of the gene transcript, we carried out a prenatal diagnosis in a fetus at risk for ATR-X syndrome by initially determining the XNP/ATR-X gene haplotype before considering gene sequencing.
Mutations in the XNP gene have been reported in alpha thalassemia/mental retardation (MR) syndrome (ATR-X) and other severe X-linked MR conditions with facial dysmorphisms.
Mecp2 is a transcriptional repressor protein that is mutated in Rett syndrome, a neurodevelopmental disorder that is the second most common cause of mental retardation in women.
The aim of the study was: (a) to evaluate the incidence and spectrum of MECP2 mutations in children with RTT and variant MR; (b) to evaluate phenotype-genotype correlations.
This case broadens the phenotypic spectrum of MECP2 abnormalities with consequent implication in diagnosis and genetic counselling of girls with non-syndromic mental retardation.
Analysis of highly conserved regions of the 3'UTR of MECP2 gene in patients with clinical diagnosis of Rett syndrome and other disorders associated with mental retardation.