This case broadens the phenotypic spectrum of MECP2 abnormalities with consequent implication in diagnosis and genetic counselling of girls with non-syndromic mental retardation.
Specific mutations in MECP2 cause Rett syndrome (RTT) in females whereas other mutations in the same gene cause several other syndromes in males, including X-linked intellectual disability (with and without spasticity) (OMIM 300055) and X-linked intellectual disability due to increased dosage of MECP2 (OMIM 300260).
Maintenance of an appropriate level of MeCP2 appears integral to the function of healthy neurons as patients with increased levels of MeCP2, owing to duplication of the Xq28 region encompassing the MECP2 locus, also present with intellectual disability and progressive neurologic symptoms.
We propose that truncating mutations in IQSEC2 are responsible for syndromic severe ID in male patients and should be screened in patients without mutations in MECP2, FOXG1, CDKL5 and MEF2C.
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.
Rett syndrome (RS), a progressive severe neurodevelopmental disorder mainly caused by de novo mutations in the X-chromosomal MeCP2 gene encoding the transcriptional regulator methyl-CpG-binding protein 2, is a leading cause of mental retardation with autistic features in females.
Rett syndrome (RTT), a neurodevelopmental disorder caused by mutations in the X-linked gene encoding methyl-CpG-binding protein2 (MeCP2), is a leading cause of mental retardation in females.
This case, as well as other published studies of males with MECP2 mutations, reveals that the clinical manifestations in viable males vary from neonates with severe encephalopathy to adults with mental retardation and demonstrate genotype-phenotype correlations.
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.
Rett syndrome (RS), an X-linked neurodevelopmental disorder and the common cause of mental retardation in females, is caused by methyl CpG binding protein 2 (MECP2) gene mutations with a frequency of more than 95% in classical Rett patients.
In 2009, four families with a distal duplication of Xq28 not including MECP2 and mediated by low-copy repeats (LCRs) designated "K" and "L" were reported with intellectual disability and epilepsy.
This finding emphasizes the need to consider MECP2 sequencing in females with non-classic Rett phenotypes, particularly those with intellectual disability and neuropsychiatric features.
Rett syndrome, a neurodevelopmental disorder caused by mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MeCP2), is a leading cause of mental retardation with autistic features in females.
Rett syndrome, the most common form of mental retardation in young girls, is due to l mutation of MECP2, encoding a methylated DNA binding protein that translates DNA methylation into gene repression.
The need for tightly controlled MeCP2 levels in brain is strongly suggested by neurologically abnormal phenotypes of mouse models with mild overexpression and by mental retardation in human males with MECP2 duplication.
Mutations in methyl-CpG-binding protein 2 (MECP2) in males can lead to various phenotypes, ranging from neonatal encephalopathy to intellectual disability.
The finding of a significant number of copy number polymorphisms in the genome in the normal population, means that assigning pathogenicity to deletions and duplications in patients with mental retardation can be difficult but has been identified for duplications of MECP2 and L1CAM.
We consider essential proceeding further screening in the whole extension of the MECP2 gene using clinically well-documented and larger sized sample to assure the overall contribution of MECP2 to mental retardation.