OBJECTIVE: Our goal was to describe the neurologic and clinical features of affected males from families with X-linked patterns of severe mental retardation, hypotonia, recurrent respiratory infection, and microduplication of Xq28 that consistently includes the MECP2 (methyl-CpG binding protein 2) gene. STUDY DESIGN: To identify duplications, multiplex ligation-dependent probe amplification of the MECP2 gene was performed on male probands from families with X-linked mental retardation. The males either had linkage to Xq28 or had a phenotype consistent with previous reports involving Xq28 functional disomy. After detection of a duplication of MECP2, additional family members were tested to confirm the MECP2 duplication segregated with the affected phenotype, and X-inactivation studies were performed on carrier females. RESULTS: Six families with multiple affected males having MECP2 duplications were identified by multiplex ligation-dependent probe amplification, and the carrier mothers were subsequently shown to have highly skewed X inactivation. In 5 of 6 families, the microduplication extended proximally to include the L1 cell adhesion molecule gene. The primary clinical features associated with this microduplication are infantile hypotonia, recurrent respiratory infection, severe mental retardation, absence of speech development, seizures, and spasticity. CONCLUSIONS: Although many of the phenotypic features of our patients are rather nonspecific in cohorts of individuals with syndromic and nonsyndromic mental retardation, the proneness to infection is quite striking because the patients had normal growth and were not physically debilitated. Although the etiology of the infections is not understood, we recommend considering MECP2 dosage studies and a genetics referral in individuals with severe developmental delay and neurologic findings, especially when a history of recurrent respiratory ailments has been documented.
OBJECTIVE: Our goal was to describe the neurologic and clinical features of affected males from families with X-linked patterns of severe mental retardation, hypotonia, recurrent respiratory infection, and microduplication of Xq28 that consistently includes the MECP2 (methyl-CpG binding protein 2) gene. STUDY DESIGN: To identify duplications, multiplex ligation-dependent probe amplification of the MECP2 gene was performed on male probands from families with X-linked mental retardation. The males either had linkage to Xq28 or had a phenotype consistent with previous reports involving Xq28 functional disomy. After detection of a duplication of MECP2, additional family members were tested to confirm the MECP2 duplication segregated with the affected phenotype, and X-inactivation studies were performed on carrier females. RESULTS: Six families with multiple affected males having MECP2 duplications were identified by multiplex ligation-dependent probe amplification, and the carrier mothers were subsequently shown to have highly skewed X inactivation. In 5 of 6 families, the microduplication extended proximally to include the L1 cell adhesion molecule gene. The primary clinical features associated with this microduplication are infantile hypotonia, recurrent respiratory infection, severe mental retardation, absence of speech development, seizures, and spasticity. CONCLUSIONS: Although many of the phenotypic features of our patients are rather nonspecific in cohorts of individuals with syndromic and nonsyndromic mental retardation, the proneness to infection is quite striking because the patients had normal growth and were not physically debilitated. Although the etiology of the infections is not understood, we recommend considering MECP2 dosage studies and a genetics referral in individuals with severe developmental delay and neurologic findings, especially when a history of recurrent respiratory ailments has been documented.
Authors: Ute Grasshoff; Michael Bonin; Ina Goehring; Arif Ekici; Andreas Dufke; Kirsten Cremer; Nicholas Wagner; Eva Rossier; Anna Jauch; Michael Walter; Claudia Bauer; Peter Bauer; Karl Horber; Stefanie Beck-Woedl; Dagmar Wieczorek Journal: Eur J Hum Genet Date: 2011-02-16 Impact factor: 4.246
Authors: Tianshu Yang; Melissa B Ramocki; Jeffrey L Neul; Wen Lu; Luz Roberts; John Knight; Christopher S Ward; Huda Y Zoghbi; Farrah Kheradmand; David B Corry Journal: Sci Transl Med Date: 2012-12-05 Impact factor: 17.956
Authors: Marijke Bauters; Hilde Van Esch; Michael J Friez; Odile Boespflug-Tanguy; Martin Zenker; Angela M Vianna-Morgante; Carla Rosenberg; Jaakko Ignatius; Martine Raynaud; Karen Hollanders; Karen Govaerts; Kris Vandenreijt; Florence Niel; Pierre Blanc; Roger E Stevenson; Jean-Pierre Fryns; Peter Marynen; Charles E Schwartz; Guy Froyen Journal: Genome Res Date: 2008-04-02 Impact factor: 9.043
Authors: Dorien Lugtenberg; Tjitske Kleefstra; Astrid R Oudakker; Willy M Nillesen; Helger G Yntema; Andreas Tzschach; Martine Raynaud; Dietz Rating; Hubert Journel; Jamel Chelly; Cyril Goizet; Didier Lacombe; Jean-Michel Pedespan; Bernard Echenne; Gholamali Tariverdian; Declan O'Rourke; Mary D King; Andrew Green; Margriet van Kogelenberg; Hilde Van Esch; Jozef Gecz; Ben C J Hamel; Hans van Bokhoven; Arjan P M de Brouwer Journal: Eur J Hum Genet Date: 2008-11-05 Impact factor: 4.246