Novel myosin mutations for hereditary hearing loss revealed by targeted genomic capture and massively parallel sequencing
| Autor: | Karen B. Avraham, Moshe Frydman, Zippora Brownstein, Anne Houdusse, Serena Sirigu, Amal Abu-Rayyan, Daphne Karfunkel-Doron, Bella Davidov, Mordechai Shohat, Moien Kanaan |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Male
Hearing loss Population Genomics Biology Myosins medicine.disease_cause Article Myosin Genetics medicine otorhinolaryngologic diseases Humans Genetic Predisposition to Disease Israel education Hearing Loss Genetics (clinical) Family Health education.field_of_study Mutation Massive parallel sequencing Base Sequence Myosin Heavy Chains Genetic heterogeneity High-Throughput Nucleotide Sequencing Phenotype Arabs Pedigree Jews Myosin VIIa Female medicine.symptom |
| Popis: | Hereditary hearing loss is genetically heterogeneous, with a large number of genes and mutations contributing to this sensory, often monogenic, disease. This number, as well as large size, precludes comprehensive genetic diagnosis of all known deafness genes. A combination of targeted genomic capture and massively parallel sequencing (MPS), also referred to as next-generation sequencing, was applied to determine the deafness-causing genes in hearing-impaired individuals from Israeli Jewish and Palestinian Arab families. Among the mutations detected, we identified nine novel mutations in the genes encoding myosin VI, myosin VIIA and myosin XVA, doubling the number of myosin mutations in the Middle East. Myosin VI mutations were identified in this population for the first time. Modeling of the mutations provided predicted mechanisms for the damage they inflict in the molecular motors, leading to impaired function and thus deafness. The myosin mutations span all regions of these molecular motors, leading to a wide range of hearing phenotypes, reinforcing the key role of this family of proteins in auditory function. This study demonstrates that multiple mutations responsible for hearing loss can be identified in a relatively straightforward manner by targeted-gene MPS technology and concludes that this is the optimal genetic diagnostic approach for identification of mutations responsible for hearing loss. |
| Databáze: | OpenAIRE |
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