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.
This study examined the effects of sedation on auditory brainstem response interpeak latency intervals (i.e., I-III, III-V, and I-V) in two groups: (1) a group with Rett syndrome who were positive for mutations in the MECP2 gene and (2) a group negative for mutations in the MECP2 gene but who were severely to profoundly delayed with other causes of mental retardation.
The purpose of this study was to investigate the role of evolutionarily conserved cis-elements in regulating the post-transcriptional expression of the MECP2 gene and to explore their possible correlations with a mutation that is known to cause mental retardation.
Mutations in MECP2 cause classic or preserved speech variant Rett syndrome and intellectual disability in females and early demise or marked neurodevelopmental handicap in males.
Only recently have mutations in MECP2 been found to be a cause of Rett Syndrome (RTT), a neuro-developmental disorder characterized by mental retardation, loss of expressive speech, deceleration of head growth and loss of acquired skills that almost exclusively affects females.
In this study we screened several cohorts of children for CDKL5 mutations, totaling 316 patients, including individuals with a clinical diagnosis of RTT but who were negative forMECP2 mutations (n=102), males with X-linked mental retardation (n=9), patients with West syndrome (n=52), patients with autism (n=59), patients with epileptic encephalopathy (n=33), patients with Aicardi syndrome (n=7) and other patients with intellectual disability with or without seizures (n=54).
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).
To date, descriptions have been published of two patients with independent familial mental retardation (MR) and two patients with sporadic MR who harbor this specific mutation in the MECP2 gene.
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.
Normal levels of the methyl CpG-binding protein 2 (MeCP2) are critical to neurologic functioning, and slight alterations result in intellectual disability and autistic features.
These findings corroborate other recent reports in the literature and highlight that the overexpression of MECP2 caused by duplications involving this gene is a relatively frequent genetic cause of mental retardation in males, highlighting the importance of MECP2 gene dosage for diagnostic purposes in such cases.
Identification of a family with nonspecific mental retardation (MRX79) with the A140V mutation in the MECP2 gene: is there a need for routine screening?
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.
Consequently, we have searched for MECP2 mutations in 294 patients (43 Angelman and Prader-Willi like included) with mental retardation (MR) of unknown aetiology.
This case broadens the phenotypic spectrum of MECP2 abnormalities with consequent implication in diagnosis and genetic counselling of girls with non-syndromic mental retardation.
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.