Multiplex Protocol Suitable for Screening for MECP2 Mutations in Girls with Mental Retardation

Abstract

In girls, mutations in the gene for methyl-CpG-binding protein 2 ( MECP2 ) are associated with clinical presentations that include classic Rett syndrome (RTT), Angelman syndrome-like phenotype, autism, and even mild forms of mental retardation (1)(2)(3)(4)(5)(6)(7). The gene, located in chromosome Xq28, is expressed in the brain, where it is involved in the growth and maturation of neurons (8)(9). MECP2 also influences expression of the genes UBE3A and GABRB3 , which may help explain the Angelman syndrome-like and/or autism phenotypes (10). In males, mutations in MECP2 can be associated with X-linked mental retardation or with severe neonatal-onset encephalopathy (11)(12). The molecular diagnosis of MECP2 mutations has been complex and expensive, depending on mutation identification using a scanning technique followed by DNA sequencing. In classic sporadic RTT, a mutation can be detected in 70%–90% of cases. However, in atypical RTT and/or familial cases, this rate drops to 34% and 29%–45%, respectively (13)(14)(15). In Angelman-like patients, MECP2 mutations are …