Variable hearing impairment in a DFNB2 family with a novel MYO7A missense mutation

Michael S Hildebrand; Natalie P Thorne; Catherine J Bromhead; Kimia Kahrizi; Jennifer A Webster; Zohreh Fattahi; Mojgan Bataejad; William J Kimberling; Dietrich Stephan; Hossein Najmabadi; Melanie Bahlo; Richard J.H Smith

doi:10.1111/j.1399-0004.2009.01344.x

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Variable hearing impairment in a DFNB2 family with a novel MYO7A missense mutation

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Variable hearing impairment in a DFNB2 family with a novel MYO7A missense mutation

Michael S Hildebrand, Natalie P Thorne, Catherine J Bromhead, Kimia Kahrizi, Jennifer A Webster, Zohreh Fattahi, Mojgan Bataejad, William J Kimberling, Dietrich Stephan, Hossein Najmabadi, …

Clinical genetics, Vol.77(6), pp.563-571

06/2010

DOI: 10.1111/j.1399-0004.2009.01344.x

PMCID: PMC2891191

PMID: 20132242

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Abstract

Myosin VIIA mutations have been associated with non-syndromic hearing loss (DFNB2; DFNA11) and Usher syndrome type 1B (USH1B). We report clinical and genetic analyzes of a consanguineous Iranian family segregating autosomal recessive non-syndromic hearing loss (ARNSHL). The hearing impairment was mapped to the DFNB2 locus using Affymetrix 50K GeneChips; direct sequencing of the MYO7A gene was completed. The Iranian family (L-1419) was shown to segregate a novel homozygous missense mutation (c.1184G>A) that results in a p.R395H amino acid substitution in the motor domain of the myosin VIIA protein. Since one affected family member had significantly less severe hearing loss we used a candidate approach to search for a genetic modifier. This novel MYO7A mutation is the first reported to cause DFNB2 in the Iranian population and this DFNB2 family is the first to be associated with a potential modifier. The absence of vestibular and retinal defects, and less severe low frequency hearing loss, is consistent with the phenotype of a recently reported Pakistani DFNB2 family. Thus, we conclude this family has non-syndromic hearing loss (DFNB2) rather than Usher syndrome type 1B (USH1B), providing further evidence that these two diseases represent discrete disorders.

myosin VIIA protein

DFNB2

MYO7A gene

genetic modifier

missense mutation

motor domain

USH1B

Details

Title: Subtitle: Variable hearing impairment in a DFNB2 family with a novel MYO7A missense mutation
Creators: Michael S Hildebrand - Department of Otolaryngology - Head and Neck Surgery, University of Iowa, Iowa City, IA, USA
Natalie P Thorne - Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
Catherine J Bromhead - Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
Kimia Kahrizi - Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
Jennifer A Webster - Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA
Zohreh Fattahi - Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
Mojgan Bataejad - Azad University, Tehran Iran
William J Kimberling - Department of Genetics, Boys Town National Research Hospital, Omaha, NE, USA
Dietrich Stephan - Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA
Hossein Najmabadi - Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
Melanie Bahlo - Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
Richard J.H Smith - Department of Otolaryngology - Head and Neck Surgery, University of Iowa, Iowa City, IA, USA
Resource Type: Journal article
Publication Details: Clinical genetics, Vol.77(6), pp.563-571
DOI: 10.1111/j.1399-0004.2009.01344.x
PMID: 20132242
PMCID: PMC2891191
NLM abbreviation: Clin Genet
ISSN: 0009-9163
eISSN: 1399-0004
Language: English
Date published: 06/2010
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Otolaryngology; Internal Medicine
Record Identifier: 9984006312202771

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