title: Clinical, Molecular, and Computational Analysis in Patients With a Novel Double Mutation and a New Synonymous Variant in MeCP2: Report of the First Missense Mutation Within the AT-hook1 Cluster in Rett Syndrome.
abstract: Rett syndrome is an X-linked neurodevelopmental disorder, primarily caused by MECP2 mutations. In this study, clinical, molecular and bioinformatics analyses were performed in Rett patients to understand the relationship between MECP2 mutation type and the clinical severity. Two double MeCP2 mutations were detected: a novel one (p.G185 V in cis with p.R255X) in P1 and a known one (p.P179 S in cis with p.R255X) in P2. Besides, a novel synonymous mutation (c.807C>T; p.G269G), which could affect mRNA splicing, was identified in P3. The results from clinical severity analysis have shown that P1 was more severely affected than P2 with CSS being 35 and 14, respectively. Therefore, the phenotypic variability in P1 and P2 could be explained by the potential pathogenic effect of the RTT-causing missense mutation p.G185 V in the AT-hook1. In conclusion, clinical, molecular, and in silico investigations in the studied patients have been proven to be substantial for the genotype-phenotype correlation.
authors.affiliation: 1 Laboratory of Molecular and Functional Genetics, Faculty of Science of Sfax, University of Sfax, Sfax, Tunisia.|2 Laboratory of Human Molecular Genetics, Faculty of Medicine, Sfax, Tunisia.
authors.forename: Marwa
authors.initials: M
authors.lastname: Kharrat
authors.affiliation: 3 Laboratory of Molecular Biotechnologie of Eukaryotes, Centre of Biotechnology of Sfax, University of Sfax, Sfax, Tunisia.
authors.forename: Yosra
authors.initials: Y
authors.lastname: Kamoun
authors.affiliation: 4 Service de Neurologie Infantile, C.H.U. Hédi Chaker de Sfax, Tunisia.
authors.forename: Fatma
authors.initials: F
authors.lastname: Kamoun
authors.affiliation: 4 Service de Neurologie Infantile, C.H.U. Hédi Chaker de Sfax, Tunisia.
authors.forename: Emna
authors.initials: E
authors.lastname: Ellouze
authors.affiliation: 2 Laboratory of Human Molecular Genetics, Faculty of Medicine, Sfax, Tunisia.
authors.forename: Marwa
authors.initials: M
authors.lastname: Maalej
authors.affiliation: 1 Laboratory of Molecular and Functional Genetics, Faculty of Science of Sfax, University of Sfax, Sfax, Tunisia.
authors.forename: Nourhene
authors.initials: N
authors.lastname: Fendri-Kriaa
authors.affiliation: 2 Laboratory of Human Molecular Genetics, Faculty of Medicine, Sfax, Tunisia.
authors.forename: Leila
authors.initials: L
authors.lastname: Ammar-Keskes
authors.affiliation: 2 Laboratory of Human Molecular Genetics, Faculty of Medicine, Sfax, Tunisia.
authors.forename: Neila
authors.initials: N
authors.lastname: Belghith
authors.affiliation: 3 Laboratory of Molecular Biotechnologie of Eukaryotes, Centre of Biotechnology of Sfax, University of Sfax, Sfax, Tunisia.
authors.forename: Ali
authors.initials: A
authors.lastname: Gargouri
authors.affiliation: 4 Service de Neurologie Infantile, C.H.U. Hédi Chaker de Sfax, Tunisia.
authors.forename: Chahnez
authors.initials: C
authors.lastname: Triki
authors.affiliation: 1 Laboratory of Molecular and Functional Genetics, Faculty of Science of Sfax, University of Sfax, Sfax, Tunisia.
authors.forename: Faiza
authors.initials: F
authors.lastname: Fakhfakh
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D019295:Computational Biology; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D008958:Models, Molecular; D020125:Mutation, Missense / Q000235:genetics*; D015518:Rett Syndrome / Q000235:genetics* / Q000503:physiopathology; D012720:Severity of Illness Index
chemical_list: C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2
keywords: AT-hook1; MECP2; Rett syndrome; chromosome X inactivation; double MECP2 mutation; p.G185 V