TY - JOUR T1 - Spectrum of mutations in the <em>MECP2</em> gene in patients with infantile autism and Rett syndrome JF - Journal of Medical Genetics JO - J Med Genet SP - e41 LP - e41 DO - 10.1136/jmg.37.12.e41 VL - 37 IS - 12 AU - CHING-WAN LAM AU - WAI-LAN YEUNG AU - CHUNG-HUNG KO AU - PRISCILLA M K POON AU - SUI-FAN TONG AU - KWOK-YIN CHAN AU - IVAN F M LO AU - LISA Y S CHAN AU - JOANNIE HUI AU - VIRGINIA WONG AU - CHI-PUI PANG AU - Y M DENNIS LO AU - TAI-FAI FOK Y1 - 2000/12/01 UR - http://jmg.bmj.com/content/37/12/e41.abstract N2 - Editor—Rett syndrome (RTT, MIM 312750) is a progressive neurological disorder, occurring almost exclusively in females during their first two years of life . RTT is one of the most common causes of mental retardation in females, with an incidence of 1 in 10 000-15 000 female births. Patients with classical RTT appear to develop normally until 6-18 months of age, then gradually lose speech and purposeful hand use, and, eventually, develop microcephaly, seizures, autism, ataxia, hyperventilation, and stereotypic hand movements. After the initial regression, the clinical condition stabilises and patients usually survive into adulthood. Laboratory investigations have not shown any metabolic abnormalities in affected subjects.1 RTT is included in the differential diagnosis of autistic disorder in girls.1-3 Qualitative abnormalities in social and communicative development and stereotypic behaviour are typically present in RTT. Definitive diagnosis is often delayed until after the loss of purposeful hand movements and the relatively characteristic hyperventilation later in childhood,1 and earlier diagnosis would be desirable.The occurrence of a few familial cases with maternal inheritance suggests that RTT is an X linked dominant mutation with lethality in hemizygous males. Previous exclusion mapping studies using RTT families identified a locus in Xq28.4-6 Using a systematic gene screening approach, Amir et al 7and Wan et al 8 have identified mutations in the MECP2 gene, which encodes methyl-CpG binding protein 2, as the cause of some RTT cases. Most of the mutations are de novo and occur at a CpG dinucleotide. The cytosine in the CpG dinucleotide is a frequent site for DNA methylation and deamination of methylated cytosine to thymine causes the transition.The MeCP2 protein silences methylated chromatin by recruiting a histone deacetylase complex.9 Unlike most other transcriptional repressor proteins, however, the binding site of MeCP2 occurs frequently in genomic DNA … ER -