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.
| De Maio, Antonia; Yalamanchili, Hari Krishna; Adamski, Carolyn J et al. (2018) RBM17 Interacts with U2SURP and CHERP to Regulate Expression and Splicing of RNA-Processing Proteins. Cell Rep 25:726-736.e7 |
| Zoghbi, Huda Y; Beaudet, Arthur L (2016) Epigenetics and Human Disease. Cold Spring Harb Perspect Biol 8:a019497 |
| Suter, Bernhard; Treadwell-Deering, Diane; Zoghbi, Huda Y et al. (2014) Brief report: MECP2 mutations in people without Rett syndrome. J Autism Dev Disord 44:703-11 |
| Glaze, Daniel G; Percy, Alan K; Motil, Kathleen J et al. (2009) A study of the treatment of Rett syndrome with folate and betaine. J Child Neurol 24:551-6 |
| Neul, J L; Fang, P; Barrish, J et al. (2008) Specific mutations in methyl-CpG-binding protein 2 confer different severity in Rett syndrome. Neurology 70:1313-21 |
| Percy, Alan K (2008) Rett syndrome: recent research progress. J Child Neurol 23:543-9 |
| Percy, Alan K; Lane, Jane B; Childers, Jerry et al. (2007) Rett syndrome: North American database. J Child Neurol 22:1338-41 |
| Alvarez-Saavedra, Matias; Saez, Mauricio A; Kang, Dongcheul et al. (2007) Cell-specific expression of wild-type MeCP2 in mouse models of Rett syndrome yields insight about pathogenesis. Hum Mol Genet 16:2315-25 |
| Moretti, Paolo; Zoghbi, Huda Y (2006) MeCP2 dysfunction in Rett syndrome and related disorders. Curr Opin Genet Dev 16:276-81 |
| Tofil, Nancy M; Buckmaster, Mark A; Winkler, Margaret K et al. (2006) Deep sedation with propofol in patients with Rett syndrome. J Child Neurol 21:857-60 |
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