Mutational analysis of methyl-CpG binding protein 2 (MECP2) gene in Indian cases of Rett syndrome

Rett syndrome (RTT) is an X-linked postnatal neurological disorder, primarily affecting females and characterized by regression, epilepsy, stereotypical hand movements, and motor abnormalities. Its prevalence is about 1 in 10,000 female births. RTT is caused by mutations within methyl CpG-binding protein 2 (MECP2) gene. Over 200 individual nucleotide changes in the gene, which cause pathogenic mutations, have been reported; however, eight most commonly occurring missense and nonsense mutations account for almost 70% of all mutations. RTT cases have also been reported from India. The phenotype (classical and atypical inclusive) has many differentials. However, a genetically based confirmed diagnosis would help in management and counseling. In this pilot study we have analyzed MECP2 mutations in ten Indian sporadic patients diagnosed clinically as having RTT. Two mutations and one novel variant in MECP2 have been detected. Missense mutations p.R133C and c.806delG have been detected. The missence mutation p.R133C was the part of eight hotspots reported in Rett patients. This patient met all the essential criteria except delayed onset of regression. The other c.806delG mutation positive patient also fulfilled all the obligatory criteria of classical RTT. Another clinically atypical Rett patient showed a novel mutation p.C339S in MECP2 gene. The preliminary result necessitates a large-scale study of RTT patients to determine more precisely the influence of MECP2 mutations in Indian patients and their correlation with clinical phenotypes.