Structural variation in Xq28: MECP2 duplications in 1% of patients with unexplained XLMR and in 2% of male patients with severe encephalopathy
Eur J Hum Genet. 2008-11-05; 17(4): 444-453
DOI: 10.1038/EJHG.2008.208
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1. Eur J Hum Genet. 2009 Apr;17(4):444-53. doi: 10.1038/ejhg.2008.208. Epub 2008 Nov
5.
Structural variation in Xq28: MECP2 duplications in 1% of patients with
unexplained XLMR and in 2% of male patients with severe encephalopathy.
Lugtenberg D(1), Kleefstra T, Oudakker AR, Nillesen WM, Yntema HG, Tzschach A,
Raynaud M, Rating D, Journel H, Chelly J, Goizet C, Lacombe D, Pedespan JM,
Echenne B, Tariverdian G, O’Rourke D, King MD, Green A, van Kogelenberg M, Van
Esch H, Gecz J, Hamel BC, van Bokhoven H, de Brouwer AP.
Author information:
(1)Department of Human Genetics, Radboud University Nijmegen Medical Centre,
Nijmegen, The Netherlands.
Erratum in
Eur J Hum Genet. 2009 May;17(5):697.
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.
DOI: 10.1038/ejhg.2008.208
PMCID: PMC2986218
PMID: 18985075 [Indexed for MEDLINE]