title: A Novel Mutation p.A59P in N-Terminal Domain of Methyl-CpG-Binding Protein 2 Confers Phenotypic Variability in 3 Cases of Tunisian Rett Patients: Clinical Evaluations and In Silico Investigations.
abstract: Rett syndrome is a monogenic X-linked dominant neurodevelopmental disorder related to mutation in MECP2, which encodes the methyl-CpG-binding protein MeCP2. The aim of this study was to search for mutations of MECP2 gene in Tunisian Rett patients and to evaluate the impact of the found variants on structural and functional features of MeCP2. The result of mutation analysis revealed that 3 Rett patients shared the same novel heterozygous point mutation c.175G>C (p.A59P). The p.A59P mutation was located in a conserved amino acid in the N-terminal segment of MeCP2. This novel mutation confers a phenotypic variability with different clinical severity scores (3, 8, and 9) and predicted by Sift and PolyPhen to be damaging. Modeling results showed that p.A59P adds 2 hydrogen bonds and changes the structural conformation of MeCP2 with a significant root mean square deviation value (9.66 Å), suggesting that this mutation could probably affect the conformation, function and stability of MeCP2.
authors: Laboratory of Human Molecular Genetics, The Sfax Faculty of Medicine, Sfax, Tunisia marwa.kharrat.feki@gmail.com.
authors: Marwa
authors: M
authors: Kharrat
authors: Service de Neurologie Infantile, C.H.U. Hédi Chaker de Sfax, Tunisia.
authors: Ines
authors: I
authors: Hsairi
authors: Laboratory of Human Molecular Genetics, The Sfax Faculty of Medicine, Sfax, Tunisia.
authors: Nourhene
authors: N
authors: Fendri-Kriaa
authors: Laboratory of Human Molecular Genetics, The Sfax Faculty of Medicine, Sfax, Tunisia.
authors: Houda
authors: H
authors: Kenoun
authors: Laboratory of Human Molecular Genetics, The Sfax Faculty of Medicine, Sfax, Tunisia.
authors: Houda Ben
authors: HB
authors: Othmen
authors: Laboratory of Human Molecular Genetics, The Sfax Faculty of Medicine, Sfax, Tunisia.
authors: Afif
authors: A
authors: Ben Mahmoud
authors: Laboratory of Human Molecular Genetics, The Sfax Faculty of Medicine, Sfax, Tunisia.
authors: Rania
authors: R
authors: Ghorbel
authors: Service de Neurologie Infantile, C.H.U. Hédi Chaker de Sfax, Tunisia.
authors: Imen
authors: I
authors: Abid
authors: Service de Neurologie Infantile, C.H.U. Hédi Chaker de Sfax, Tunisia.
authors: Chahnez
authors: C
authors: Triki
authors: Laboratory of Human Molecular Genetics, The Sfax Faculty of Medicine, Sfax, Tunisia.
authors: Faiza
authors: F
authors: Fakhfakh
mesh_terms: D002648:Child; D005260:Female; D006801:Humans; D006860:Hydrogen Bonding; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D008958:Models, Molecular; D009154:Mutation; D010641:Phenotype; D015518:Rett Syndrome / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D012720:Severity of Illness Index; D014416:Tunisia
chemical_list: C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2
keywords: MECP2 gene; N-terminal region; Rett syndrome; clinical severity scores; homology modeling; p.A59P