This study proposes to map and isolate the gene for Rett syndrome, a central nervous disorder most commonly seen in females, using rare familial cases. The applicant will test the hypothesis that Rett syndrome (RS) is an X-linked dominant condition, with non-penetrant female carriers determined in part by X inactivation patterns. The applicant will extend preliminary mapping experiments that have localized the RS gene to Xq28 and narrow the candidate map interval. They will then screen for deletions within Xq28 in a number of sporadic cases, as an approach to fine map the RS gene by loss-of-heterozygosity studies. Detailed physical mapping to define physical rearrangements in Xq28 will serve as a basis for testing candidate expressed sequence tags (ESTs) from within the critical region and for eventual gene and protein characterization.
| Thistlethwaite, William A; Moses, Linda M; Hoffbuhr, Kristen C et al. (2003) Rapid genotyping of common MeCP2 mutations with an electronic DNA microchip using serial differential hybridization. J Mol Diagn 5:121-6 |
| Hoffbuhr, K C; Moses, L M; Jerdonek, M A et al. (2002) Associations between MeCP2 mutations, X-chromosome inactivation, and phenotype. Ment Retard Dev Disabil Res Rev 8:99-105 |
| Hoffbuhr, K; Devaney, J M; LaFleur, B et al. (2001) MeCP2 mutations in children with and without the phenotype of Rett syndrome. Neurology 56:1486-95 |
