title: A novel missense mutation in the ESRRB gene causes DFNB35 hearing loss in a Tunisian family.
abstract: Autosomal recessive non-syndromic hearing loss (ARNSHL) is a genetically heterogenous disorder with 41 genes so far identified. Among these genes, ESRRB whose mutations are responsible for DFNB35 hearing loss in Pakistani and Turkish families. This gene encodes the estrogen-related receptor beta. In this study, we report a novel mutation (p.Y305H) in the ESRRB gene in a Tunisian family with ARNSHL. This mutation was not detected in 100 healthy individuals. Molecular modeling showed that the p.Y305H mutation is likely to alter the conformation of the ligand binding-site by destabilizing the coactivator binding pocket. Interestingly, this ligand-binding domain of the ESRRB protein has been affected in 5 out of 6 mutations causing DFNB35 hearing loss. Using linkage and DHPLC analysis, no more mutations were detected in the ESRRB gene in other 127 Tunisian families with ARNSHL indicating that DFNB35 is most likely to be a rare type of ARNSHL in the Tunisian population.
authors.affiliation: Equipe Procédés de Criblages Moléculaires et Cellulaires, Laboratoire de Microorganismes et de Biomolécules, Centre de Biotechnologie de Sfax, Université de Sfax, Tunisia.
authors.forename: Mariem
authors.initials: M
authors.lastname: Ben Saïd
authors.forename: Leila
authors.initials: L
authors.lastname: Ayedi
authors.forename: Melek
authors.initials: M
authors.lastname: Mnejja
authors.forename: Bochra
authors.initials: B
authors.lastname: Hakim
authors.forename: Ayda
authors.initials: A
authors.lastname: Khalfallah
authors.forename: Ilhem
authors.initials: I
authors.lastname: Charfeddine
authors.forename: Chamseddine
authors.initials: C
authors.lastname: Khifagi
authors.forename: Khalil
authors.initials: K
authors.lastname: Turki
authors.forename: Hammadi
authors.initials: H
authors.lastname: Ayadi
authors.forename: Zeineb
authors.initials: Z
authors.lastname: Benzina
authors.forename: Abdelmonem
authors.initials: A
authors.lastname: Ghorbel
authors.forename: Ignacio Del
authors.initials: ID
authors.lastname: Castillo
authors.forename: Saber
authors.initials: S
authors.lastname: Masmoudi
authors.forename: Mounira Hmani-
authors.initials: MH
authors.lastname: Aifa
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D016022:Case-Control Studies; D002874:Chromosome Mapping; D003241:Consanguinity; D016172:DNA Fingerprinting; D004252:DNA Mutational Analysis; D005260:Female; D005808:Genes, Recessive; D008040:Genetic Linkage; D056426:Genetic Loci / Q000235:genetics*; D034381:Hearing Loss / Q000235:genetics*; D006801:Humans; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D011960:Receptors, Estrogen / Q000235:genetics*; D014416:Tunisia
chemical_list: C490918:ESRRB protein, human; D011960:Receptors, Estrogen