Deleterious mutations in exon 1 of  MECP2 in Rett syndrome

• Published in: European journal of medical genetics Vol. 49; no. 4; pp. 313 - 322
• Main Authors: Quenard, Aline, Yilmaz, Saliha, Fontaine, Hervé, Bienvenu, Thierry, Moncla, Anne, des Portes, Vincent, Rivier, François, Mathieu, Michèle, Raux, Grégory, Jonveaux, Philippe, Philippe, Christophe
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Masson SAS 01.07.2006; Elsevier
• Subjects: Biological and medical sciences; Child, Preschool; Cognitive science; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Deleterious mutation; Exon 1; Exons - genetics; Female; Fundamental and applied biological sciences. Psychology; General aspects. Genetic counseling; Genetics of eukaryotes. Biological and molecular evolution; Humans; MeCP2 isoforms; Medical genetics; Medical sciences; Methyl-CpG-Binding Protein 2 - genetics; Molecular and cellular biology; Mutation; Neurology; Neuroscience; Rett; Rett Syndrome - genetics; MeCP2 isoforms; Rett; Exon 1; Deleterious mutation; Human; Nervous system diseases; Cerebral disorder; Genetic disease; Exon; Central nervous system disease; Rett syndrome; Genetics; Degenerative disease; Mutation
• ISSN: 1769-7212; 1878-0849
• DOI: 10.1016/j.ejmg.2005.11.002

The MECP2 gene is responsible for 80–85% of typical cases of Rett syndrome with deleterious mutations affecting exons 3 and 4. Recently, an alternate transcript including exon 1 was discovered with a new protein isoform (MeCP2_e1) much more abundant in brain. We screened exon 1 of MECP2 for mutations and for large rearrangements in a panel of 212 typical cases of Rett syndrome and one family case with atypical Rett syndrome. We identified two deleterious mutations (c.48_55dup and c.62+2_62+3del) and four large rearrangements encompassing exon 1 of MECP2. We also identified the c.16_21dup alteration formerly reported as c.3_4insGCCGCC and give additional support to classify this sequence variation as polymorphic. In our large panel of typical Rett, mutations affecting exon 1 of MECP2 represent 1% of the deleterious alleles. This study confirms that mutations in exon 1 of MECP2 are a rare cause of Rett syndrome.