Genetics of Rett syndrome: properties of the newly discovered gene and pathobiology of the disorder

The recent identification of mutations in the gene methyl-Cpg-binding protein-a (MECP2) in girls with Rett syndrome (RS) has firmly established the molecular genetic basis of this unique, X-linked, dominant disorder and provides a dramatic conclusion to an intensive, decade-long search. This finding has ramifications far beyond establishing the gene for RS, Recent data indicate that the clinical phenotypes for MECP2 mutations range from mild disability in the mother of a girl with RS to rapidly progressive encephalopathy in her brother. Further, the pathobiology of MECP2 could be a prototype for other disorders of neurodevelopment. MECP2 encodes a methyl-CpG-binding protein (MeCP2), which is critical for transcriptional silencing of an as yet unknown number and type of genes responsible for the pathobiology of RS. As such, this discovery opens up completely new vistas as to fundamental neurobiologic processes, to disease mechanisms in the neurodevelopmental disabilities, and to potential new therapeutic strategies for RS and related disorders. (C) 2000 Lippincott Williams & Wilkins, Inc.