Methyl-CpG-binding protein 2 gene mutations and its association with epilepsy: a single centre study from the Indian subcontinent

Rett syndrome (RTT) is an X-linked disorder caused by mutations in MECP2 in majority of cases. It is characterized by arrested development between 6 and 18 months of age, regression of acquired hand skills and speech, stereotypic hand movements, gait abnormalities and seizures. There are a very few studies in India which illustrates mutation spectrum in RTT. None of the studies have correlated seizures with the genotype. This study describes the phenotype and genotype spectrum in children with RTT syndrome and analyses the association of epilepsy with various clinical features and molecular findings. All children with RTT in our cohort had global developmental delay. Genetic diagnosis identified mutations of the MECP2 in all 25 children where RTT was suspected. We have identified point mutations in 20 patients, one insertion and four deletions by Sanger sequencing, namely c.1164_1207 (44 bp), c.1165_1207 (43 bp), c.1157_1197 (41 bp) del and c.1157_1188 (32 bp). Clinically, none of the patients with deletion had seizures. We identified one novel insertion variant c.337_338 (p.S113Ffs*9). All the deletions were located in the C-terminal region. Majority of the mutations (22/25) were identified in exon 4 which comprised of nonsense and missense types. Screening of hotspot mutations in exon 4 should be the first line evaluation in diagnosis of RTT. Molecular testing could help in specific management of seizures in RTT.

Rett syndrome: a neurodevelopmental disorder

Rett Syndrome is a rare genetic disorder caused by a mutation on the MECP2 gene on the X chromosome. It classically presents with neuroregression, loss of purposeful hand use, stereotypical involuntary hand wringing movements, an ataxic gait and acquired microcephaly with a large proportion of patients developing seizures. The authors present the case of a 3.5 year old girl with severe global developmental delay and regression, loss of purposeful hand use and an ataxic gait for 2 years and seizures since 5 days along with microcephaly with involuntary hand movements but no classic wringing movements with no significant findings on MRI and EEG and diagnosed with Rett Syndrome on the basis of genetic testing.

Association study of the gene MeCP2 polymorphisms with schizophrenia in female / 中华行为医学与脑科学杂志

Objective To explore the association of methyl-CpG-binding protein2 (MeCP2) polymorphisms with female schizophrenia in Chinese Han population.Methods By using the technology based on microarray Chip,gene polymorphism analysis of 4 locus located in the gene MeCP2 was performed in 126 schizophrenia patients fulfilled with DSM-Ⅳ-TR criteria for schizophrenia and in 144 healthy controls.Chi square test was used to compare the inter-group differences of genotypic and allelic distribution.Haplotype case-control association analysis based on linkage disequilibrium was conducted using SNP stats online software after the data was screened.The significance of results was corrected by permutation test.Results To the point of Locus rs1616369 which located in Gene MeCP2,the distribution of the genotype G/A between two groups(24.8％ vs 34.3％) reached significance (P＜0.05) ; rs3027933,genotype G/C(25.6％ vs 34.8％),P＜0.05 ; rs17435,genotype T/A(25.6％ vs 35.5％),P ＜ 0.05 ; rs2239464,genotype C/A (58.5％ vs 71.8％),P＜ 0.05.The distribution prevalence of Haplotype GCCA was 0.1581 in case group,and 0.2389 in control group,reached significant difference(P＜0.05).Conclusion As to female MeCP2 gene,the genotype on the four locations might associate with the onset of schizophrenia,MeCP2 might be susceptibility gene of female schizophrenia.The Haplotype GCCA maybe the protective factor.

Progress of diagnosis and treatment of Rett syndrome / 中华实用儿科临床杂志

Rett syndrome (RTT) is a disorder characterized by regression of spoken language and hand use,distinctive hand stereotypies,accompanying with severe psychomotor developmental retardation and retrogression.RTT becomes recognizable at 6-18 months and female are absolutely susceptive.MECP2 mutations are closely related to the development of RTT.Revised diagnostic criteria for RTT (2010) ensure a high degree of homogeneity in cases enrolled in treatment and clinical studies throughout the world.As for the treatment,no crucial advancement has been clinically applied recently,but some valuable basic research is in progress.This paper reviews the genetic research,clinical diagnosis and treatment of RTT,and promotes understanding of the new diagnostic criteria and basic research.