Abstract
Xq28 duplications including MECP2 are a well-known cause of severe mental retardation in males with seizures, muscular hypotonia, progressive spasticity, poor speech and recurrent infections that often lead to early death. Female carriers usually show a normal intellectual performance due to skewed X-inactivation (XCI). We report on two female patients with a de novo MECP2 duplication associated with moderate mental retardation. In both patients, the de novo duplication occurred on the paternal allele, and both patients show a random XCI, which can be assumed as the triggering factor for the phenotype. Furthermore, we describe the phenotype that might be restricted to unspecific mild-to -moderate mental retardation with neurological features in early adulthood.
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Acknowledgements
This study would not have been possible without the invaluable assistance of the patients and their families. We wish to thank the cooperating physicians for referral of the patients to our departments, especially G Dissemond, L Kämmerling and V Horber. We also thank Bernhard Horsthemke, André Reis and Olaf Riess for continuous support, as well as Juliane Hoyer and Markus Zweier for their essential help. The Institutes for Human Genetics, Essen, Erlangen, Heidelberg and Tübingen, Germany, are members of the ‘German Mental Retardation Network’ (MRNET), which is funded by the German Federal Ministry of Education and Research (BMBF) as a part of the National Genome Research Network (http://www.ngfn.de/en/retardierung.html, project reference numbers 01GS08164, 01GS0816, 01GS08168, 01GS08162).
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Grasshoff, U., Bonin, M., Goehring, I. et al. De novo MECP2 duplication in two females with random X-inactivation and moderate mental retardation. Eur J Hum Genet 19, 507–512 (2011). https://doi.org/10.1038/ejhg.2010.226
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DOI: https://doi.org/10.1038/ejhg.2010.226
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