Novel myosin mutations for hereditary hearing loss revealed by targeted genomic capture and massively parallel sequencing

Zippora Brownstein, Amal Abu-Rayyan, Daphne Karfunkel-Doron, Serena Sirigu, Bella Davidov, Mordechai Shohat, Moshe Frydman, Anne Houdusse, Moien Kanaan, Karen B. Avraham*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)768-775
Number of pages8
JournalEuropean Journal of Human Genetics
Issue number6
StatePublished - Jun 2014


FundersFunder number
ARC subvention fixeSFI20121205398
Hedrich Charitable Trust
I-CORE Gene Regulation in Complex Human Disease Center41/11
National Institutes of Health
National Institute on Deafness and Other Communication DisordersR01DC011835
Kansas Bioscience Authority
Agence Nationale de la Recherche
Fondation pour la Recherche Médicale


    • consanguinity
    • deafness
    • diagnosis
    • exome sequencing
    • next-generation sequencing


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