title: Clinical profiles of four patients with Rett syndrome carrying a novel exon 1 mutation or genomic rearrangement in the MECP2 gene.
abstract: Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the X-linked MECP2 gene encoding methyl CpG binding protein 2 (MeCP2). Recently, a new isoform of MeCP2 including exon 1 was identified. This new isoform is more abundantly expressed in brain than the isoform including exons 2-4. Very little is known about the phenotypes associated with mutations in exon 1 of MECP2 since only a limited number of RTT patients carrying such mutations have been identified so far. In this study, we screened a cohort of 20 girls with RTT for exon 1 mutations by sequencing and multiplex ligation-dependent probe amplification (MLPA). We identified one girl with a novel exon 1 mutation (c.30delCinsGA) by sequencing and three with genomic rearrangements by MLPA. Comparison of the phenotypes showed that the girls carrying a mutation or rearrangement encompassing exon 1 were more severely affected than the girls with rearrangements not affecting exon 1.
authors.affiliation: Institute of Medical Genetics, University of Zurich, Schwerzenbach. bartholdi@medgen.unizh.ch
authors.forename: D
authors.initials: D
authors.lastname: Bartholdi
authors.forename: A
authors.initials: A
authors.lastname: Klein
authors.forename: M
authors.initials: M
authors.lastname: Weissert
authors.forename: N
authors.initials: N
authors.lastname: Koenig
authors.forename: A
authors.initials: A
authors.lastname: Baumer
authors.forename: E
authors.initials: E
authors.lastname: Boltshauser
authors.forename: A
authors.initials: A
authors.lastname: Schinzel
authors.forename: W
authors.initials: W
authors.lastname: Berger
authors.forename: G
authors.initials: G
authors.lastname: Mátyás
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005091:Exons; D005260:Female; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics* / Q000378:metabolism; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D015518:Rett Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D017384:Sequence Deletion
chemical_list: C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2