title: Deleterious mutations in exon 1 of MECP2 in Rett syndrome.
abstract: 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.
authors.affiliation: Laboratoire de Génétique, EA 3441, CHU Brabois, avenue du Morvan, 54511 Vandoeuvre-les-Nancy cedex, France.
authors.forename: Aline
authors.initials: A
authors.lastname: Quenard
authors.forename: Saliha
authors.initials: S
authors.lastname: Yilmaz
authors.forename: Hervé
authors.initials: H
authors.lastname: Fontaine
authors.forename: Thierry
authors.initials: T
authors.lastname: Bienvenu
authors.forename: Anne
authors.initials: A
authors.lastname: Moncla
authors.forename: Vincent
authors.initials: V
authors.lastname: des Portes
authors.forename: François
authors.initials: F
authors.lastname: Rivier
authors.forename: Michèle
authors.initials: M
authors.lastname: Mathieu
authors.forename: Grégory
authors.initials: G
authors.lastname: Raux
authors.forename: Philippe
authors.initials: P
authors.lastname: Jonveaux
authors.forename: Christophe
authors.initials: C
authors.lastname: Philippe
mesh_terms: D002675:Child, Preschool; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D009154:Mutation; D015518:Rett Syndrome / Q000235:genetics*
chemical_list: C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2