Clinical pathophysiology of Rett and MECP2 mutations

Baylor College Of Medicine, Houston TX

Investigators

Linked publications & trials

Abstract

Project 2 will study the clinical pathophysiology of Rett Syndrome (RTT) and MECP2 mutations. Three specific aims will be addressed. Mutations in the MECP2 gene have been shown to cause a wide phenotypic spectrum ranging from mild learning disabilities to classic RTT in females and several neonatal encephalopathy in males. Females with some features of RTT or mental retardation of unknown etiology may have mutations in the MECP2 gene. MECP2 mutations may also be responsible for variant cases and have a specific phenotype/genotype formulation distinct from classic RTT. (1) To define the phenotypic spectrum of children with MECP2 mutations, we will study 150 girls who are known to display autistic features, learning disabilities, or non- syndromic mental retardation of unknown etiology and 25 siblings or near relatives of girls with RTT who have associated learning or behavior problems. (2) To carry out extensive phenotype/genotype correlation studies in RTT, we will study 200 girls with classic RTT and 50 girls with atypical RTT. To accomplish these two specific aims, clinical data will be collected and blood will be obtained for DNA mutational analysis to be conducted by r. Zoghbi (Project 1). (3) The combined results of this program project will improve our understanding of the pathogenesis and enhance our ability to make the diagnosis of RTT and extend diagnosis to other neurodevelopmental disorders.