A novel missense mutation in the ESRRB gene causes DFNB35 hearing loss in a Tunisian family
| Autor: | Melek Mnejja, Mariem Ben Said, Ayda Khalfallah, Zeineb Benzina, Ignacio del Castillo, Khalil Turki, Leila Ayedi, Bochra Hakim, Mounira Hmani Aifa, Abdelmonem Ghorbel, Hammadi Ayadi, Ilhem Charfeddine, Saber Masmoudi, Chamseddine Khifagi |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Male Models Molecular Tunisia Adolescent Genetic Linkage Hearing loss DNA Mutational Analysis Molecular Sequence Data Mutation Missense Tunisian population Genes Recessive Biology ESRRB gene medicine.disease_cause Consanguinity Coactivator otorhinolaryngologic diseases Genetics medicine Humans Missense mutation Amino Acid Sequence Hearing Loss Gene Genetics (clinical) Mutation Chromosome Mapping General Medicine DNA Fingerprinting Molecular biology Pedigree Receptors Estrogen Genetic Loci Case-Control Studies Female medicine.symptom Novel mutation |
| Zdroj: | European Journal of Medical Genetics. 54:e535-e541 |
| ISSN: | 1769-7212 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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