title: A case of a Tunisian Rett patient with a novel double-mutation of the MECP2 gene.
abstract: Rett syndrome is an X-linked dominant disorder caused frequently by mutations in the methyl-CpG-binding protein 2 gene (MECP2). Rett patients present an apparently normal psychomotor development during the first 6-18 months of life. Thereafter, they show a short period of developmental stagnation followed by a rapid regression in language and motor development. The aim of this study was to perform a mutational analysis of the MECP2 gene in a classical Rett patient by sequencing the corresponding gene and modeling the found variants. The results showed the presence of a double-mutation: a new and de novo mutation c.535C>T (p.P179S) and the common c.763C>T (p.R255X) transition of the MECP2 gene. The p.P179S mutation was located in a conserved amino acid in CRIR domain (corepressor interacting region). Modeling results showed that the P179S transition could change local electrostatic properties by adding a negative charge due to serine hydroxyl group of this region of MeCP2 which may affect the function and stability of the protein. The p.R255X mutation is located in TRD-NLS domain (transcription repression domain-nuclear localization signal) of MeCP2 protein.
authors.affiliation: Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, Université de Sfax, Tunisia. nourhene.fendri@gmail.com
authors.forename: Nourhene
authors.initials: N
authors.lastname: Fendri-Kriaa
authors.forename: Ines
authors.initials: I
authors.lastname: Hsairi
authors.forename: Chamseddine
authors.initials: C
authors.lastname: Kifagi
authors.forename: Emna
authors.initials: E
authors.lastname: Ellouze
authors.forename: Emna
authors.initials: E
authors.lastname: Mkaouar-Rebai
authors.forename: Chahnez
authors.initials: C
authors.lastname: Triki
authors.forename: Faiza
authors.initials: F
authors.lastname: Fakhfakh
mesh_terms: D000595:Amino Acid Sequence; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D017434:Protein Structure, Tertiary; D015518:Rett Syndrome / Q000097:blood / Q000235:genetics*; D055672:Static Electricity
chemical_list: D051783:Methyl-CpG-Binding Protein 2