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Molecular screening of MECP2 gene in a cohort of Lebanese patients suspected with Rett syndrome: report on a mild case with a novel indel mutation
Author(s) -
Corbani S.,
Chouery E.,
Fayyad J.,
Fawaz A.,
El Tourjuman O.,
Badens C.,
Lacoste C.,
Delague V.,
Megarbane A.
Publication year - 2012
Publication title -
journal of intellectual disability research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.941
H-Index - 104
eISSN - 1365-2788
pISSN - 0964-2633
DOI - 10.1111/j.1365-2788.2011.01479.x
Subject(s) - rett syndrome , mecp2 , genetics , exon , microcephaly , mutation , genotype , neurodevelopmental disorder , cohort , biology , gene , pediatrics , medicine , phenotype
Background Rett syndrome (RTT), an X‐linked, dominant, neurodevelopment disorder represents 10% of female subjects with profound intellectual disability. Mutations in the MECP2 gene are responsible for up to 95% of the classical RTT cases, and nearly 500 different mutations distributed throughout the gene have been reported. Methods We report here the molecular study of two isoforms, MECP2_e1 and MECP2_e2 , in 45 Lebanese girls presenting developmental delay and at least one of the following features: microcephaly, neurodegeneration, abnormal behaviour, stereotypical hand movements, teeth grinding and difficulty in walking. Mutation screening was performed by denaturating high‐performance liquid chromatography combined with direct sequencing. Results Sixteen variants were noted, of which 14 have been previously reported: five suspected polymorphisms and nine mutations. Two variants were novel mutations in exon 4: c.1093_1095delGAG (p.E365del) and c.1164_1184delACCTCCACCTGAGCCCGAGAGinsCTGAGCCCCAGGACTTGAGCA (p.P388PfsX389). The deletion was found in an 8‐year‐old girl with typical clinical features of RTT. The indel was found in a 6‐year‐old girl with a very mild phenotype. Conclusion Genotype/phenotype correlation is discussed and the importance of a molecular study of MECP2 gene in patients with very mild features or a regression after the age of 2 is raised.