Increased MECP2 gene copy number as the result of genomic duplication in neurodevelopmentally delayed males

Daniela Del Gaudio, Ping Fang, Fernando Scaglia, Patricia A. Ward, William J. Craigen, Daniel G. Glaze, Jeffrey L. Neul, Ankita Patel, Jennifer A. Lee, Mira Irons, Susan A. Berry, Amber A. Pursley, Theresa A. Grebe, Debra Freedenberg, Rick A. Martin, Gary E. Hsich, Jena R. Khera, Neil R. Friedman, Huda Y. Zoghbi, Christine M. EngJames R. Lupski, Arthur L. Beaudet, Sau Wai Cheung, Benjamin B. Roa

Research output: Contribution to journalArticlepeer-review

231 Scopus citations


PURPOSE: Mutations in the MECP2 gene are associated with Rett syndrome, an X-linked mental retardation disorder in females. Mutations also cause variable neurodevelopmental phenotypes in rare affected males. Recent clinical testing for MECP2 gene rearrangements revealed that entire MECP2 gene duplication occurs in some males manifesting a progressive neurodevelopmental syndrome. METHODS: Clinical testing through quantitative DNA methods and chromosomal microarray analysis in our laboratories identified seven male patients with increased MECP2 gene copy number. RESULTS: Duplication of the entire MECP2 gene was found in six patients, and MECP2 triplication was found in one patient with the most severe phenotype. The Xq28 duplications observed in these males are unique and vary in size from approximately 200 kb to 2.2 Mb. Three of the mothers who were tested were asymptomatic duplication carriers with skewed X-inactivation. In silico analysis of the Xq28 flanking region showed numerous low-copy repeats with potential roles in recombination. CONCLUSIONS: These collective data suggest that increased MECP2 gene copy number is mainly responsible for the neurodevelopmental phenotypes in these males. These findings underscore the allelic and phenotypic heterogeneity associated with the MECP2 gene and highlight the value of molecular analysis for patient diagnosis, family members at risk, and genetic counseling.

Original languageEnglish
Pages (from-to)784-792
Number of pages9
JournalGenetics in Medicine
Issue number12
StatePublished - Dec 2006
Externally publishedYes


Dive into the research topics of 'Increased MECP2 gene copy number as the result of genomic duplication in neurodevelopmentally delayed males'. Together they form a unique fingerprint.

Cite this