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
Autor: | Rania Ghorbel, Nourhene Fendri-Kriaa, Afif Ben Mahmoud, Marwa Kharrat, Ines Hsairi, Houda Kenoun, Houda Ben Othmen, Imen Abid, Chahnez Triki, Faiza Fakhfakh |
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Rok vydání: | 2015 |
Předmět: |
Models
Molecular congenital hereditary and neonatal diseases and abnormalities Tunisia Methyl-CpG-Binding Protein 2 In silico Rett syndrome Biology Severity of Illness Index MECP2 Neurodevelopmental disorder mental disorders Rett Syndrome medicine Humans Homology modeling Child Genetics Sequence Homology Amino Acid Point mutation Hydrogen Bonding medicine.disease Molecular biology nervous system diseases Phenotype Mutation Pediatrics Perinatology and Child Health Mutation (genetic algorithm) Mutation testing Female Neurology (clinical) |
Zdroj: | Journal of Child Neurology. 30:1715-1721 |
ISSN: | 1708-8283 0883-0738 |
Popis: | 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. |
Databáze: | OpenAIRE |
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