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| ID:
473314.0,
MPI für molekulare Genetik / Department of Human Molecular Genetics |
| Structural variation in Xq28: MECP2 duplications in 1% of patients with unexplained XLMR and in 2% of male patients with severe encephalopathy |
| Authors: | Lugtenberg, Dorien; Kleefstra, Tjitske; Oudakker, Astrid R.; Nillesen, Willy M.; Yntema, Helger G.; Tzschach, Andreas; Raynaud, Martine; Rating, Dietz; Journel, Hubert; Chelly, Jamel; Goizet, Cyril; Lacombe, Didier; Pedespan, Jean-Michel; Echenne, Bernard; Tariverdian, Gholamali; O'Rourke, Declan; King, Mary D.; Green, Andrew; van Kogelenberg, Margriet; Van Esch, Hilde; Gecz, Jozef; Hamel, Ben C. J.; van Bokhoven, Hans; de Brouwer, Arjan P. M. | | Language: | English | | Date of Publication (YYYY-MM-DD): | 2009-04 | | Title of Journal: | European Journal of Human Genetics | | Journal Abbrev.: | Eur J Hum Genet | | Volume: | 17 | | Issue / Number: | 4 | | Start Page: | 444 | | End Page: | 453 | | Copyright: | © 2009 European Society of Human Genetics | | Review Status: | not specified | | Audience: | Experts Only | | Abstract / Description: | Duplications in Xq28 involving MECP2 have been described in patients with severe mental retardation, infantile hypotonia, progressive spasticity, and recurrent infections. However, it is not yet clear to what extent these and accompanying symptoms may vary. In addition, the frequency of Xq28 duplications including MECP2 has yet to be determined in patients with unexplained X-linked mental retardation and (fe)males with severe encephalopathy. In this study, we used multiplex ligation-dependent probe amplification to screen Xq28 including MECP2 for deletions and duplications in these patient cohorts. In the group of 283 patients with X-linked mental retardation, we identified three Xq28 duplications including MECP2, which suggests that approximately 1% of unexplained X-linked mental retardation may be caused by MECP2 duplications. In addition, we found three additional MECP2 duplications in 134 male patients with mental retardation and severe, mostly progressive, neurological symptoms, indicating that the mutation frequency could be as high as 2% in this group of patients. In 329 female patients, no Xq28 duplications were detected. In total, we assessed 13 male patients with a MECP2 duplication from six unrelated families. Moderate to severe mental retardation and childhood hypotonia was noted in all patients. The majority of the patients also presented with absent speech, seizures, and progressive spasticity as well as ataxia or an ataxic gait and cerebral atrophy, two previously unreported symptoms. We propose to implement DNA copy number testing for MECP2 in the current diagnostic testing in all males with moderate to severe mental retardation accompanied by (progressive) neurological symptoms. | | Free Keywords: | MECP2; Xq28; XLMR; Encephalopathy; Duplications | | Comment of the Author/Creator: | email: T.Kleefstra@antrg.umcn.nl | | External Publication Status: | published | | Document Type: | Article |
| Communicated by: | Hans-Hilger Ropers | | Affiliations: | MPI für molekulare Genetik
| | External Affiliations: | Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Department of Paediatric Neurology, University Children's Hospital, Heidelberg, Germany
CH de Vannes, Génétique Médicale, Vannes, France
Institut Cochin (IC), Département de Génétique et Pathologie Moléculaire GDPM, Equipe de Génétique et Physiopathologie du Retard Mental GPRM, Paris, France
Service de Génétique Médicale, Hôpital Pellegrin-Enfants, CHU de Bordeaux, France
Service de Neuropédiatrie Hôpital Saint-Eloi, CHU de Institute for Human Genetics, University Heidelberg, Heidelberg, Germany
Children's University Hospital, Limited Liability Company (Limited by Shares), Dublin, Ireland
Our Lady's Hospital, Crumlin and The Children's University Hospital, Dublin, Ireland
Department of Paediatrics and Child Health, Dunedin School Center for Human Genetics, University Hospital Leuven, Leuven, Belgium
Department of Genetic Medicine, Women's and Children's Hospital and Department of Paediatrics, University of Adelaide, Adelaide, Australia
| | Identifiers: | DOI:10.1038/ejhg.2008.208
ISSN:1018-4813
URL:http://www.nature.com/ejhg/journal/v17/n4/pdf/ejhg... | |
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