Copy number variants are a common cause of non-syndromic hearing loss

A Eliot Shearer; Diana L Kolbe; Hela Azaiez; Christina M Sloan; Kathy L Frees; Amy E Weaver; Erika T Clark; Carla J Nishimura; E Ann Black-Ziegelbein; Richard J H Smith

doi:10.1186/gm554

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Copy number variants are a common cause of non-syndromic hearing loss

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Copy number variants are a common cause of non-syndromic hearing loss

A Eliot Shearer, Diana L Kolbe, Hela Azaiez, Christina M Sloan, Kathy L Frees, Amy E Weaver, Erika T Clark, Carla J Nishimura, E Ann Black-Ziegelbein and Richard J H Smith

Genome medicine, Vol.6(5), pp.37-37

2014

DOI: 10.1186/gm554

PMCID: PMC4067994

PMID: 24963352

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Abstract

Background: Copy number variants (CNVs) are a well-recognized cause of genetic disease; however, methods for their identification are often gene-specific, excluded as 'routine' in screens of genetically heterogeneous disorders, and not implemented in most next-generation sequencing pipelines. For this reason, the contribution of CNVs to non-syndromic hearing loss (NSHL) is most likely under-recognized. We aimed to incorporate a method for CNV identification as part of our standard analysis pipeline and to determine the contribution of CNVs to genetic hearing loss. Methods: We used targeted genomic enrichment and massively parallel sequencing to isolate and sequence all exons of all genes known to cause NSHL. We completed testing on 686 patients with hearing loss with no exclusions based on type of hearing loss or any other clinical features. For analysis we used an integrated method for detection of single nucleotide changes, indels and CNVs. CNVs were identified using a previously published method that utilizes median read-depth ratios and a sliding-window approach. Results: Of 686 patients tested, 15.2% (104) carried at least one CNV within a known deafness gene. Of the 38.9% (267) of individuals for whom we were able to determine a genetic cause of hearing loss, a CNV was implicated in 18.7% (50). We identified CNVs in 16 different genes including 7 genes for which no CNVs have been previously reported. CNVs of STRC were most common (73% of CNVs identified) followed by CNVs of OTOA (13% of CNVs identified). Conclusion: CNVs are an important cause of NSHL and their detection must be included in comprehensive genetic testing for hearing loss.

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Title: Subtitle: Copy number variants are a common cause of non-syndromic hearing loss
Creators: A Eliot Shearer - Department of Otolaryngology - Head and Neck Surgery, Molecular Otolaryngology & Renal Research Labs, University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242, USA
Diana L Kolbe - Department of Otolaryngology - Head and Neck Surgery, Molecular Otolaryngology & Renal Research Labs, University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242, USA
Hela Azaiez - Department of Otolaryngology - Head and Neck Surgery, Molecular Otolaryngology & Renal Research Labs, University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242, USA
Christina M Sloan - Department of Otolaryngology - Head and Neck Surgery, Molecular Otolaryngology & Renal Research Labs, University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242, USA
Kathy L Frees - Department of Otolaryngology - Head and Neck Surgery, Molecular Otolaryngology & Renal Research Labs, University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242, USA
Amy E Weaver - Department of Otolaryngology - Head and Neck Surgery, Molecular Otolaryngology & Renal Research Labs, University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242, USA
Erika T Clark - Department of Otolaryngology - Head and Neck Surgery, Molecular Otolaryngology & Renal Research Labs, University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242, USA
Carla J Nishimura - Department of Otolaryngology - Head and Neck Surgery, Molecular Otolaryngology & Renal Research Labs, University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242, USA
E Ann Black-Ziegelbein - Department of Otolaryngology - Head and Neck Surgery, Molecular Otolaryngology & Renal Research Labs, University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242, USA
Richard J H Smith - Department of Otolaryngology - Head and Neck Surgery, Molecular Otolaryngology & Renal Research Labs, University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242, USA
Resource Type: Journal article
Publication Details: Genome medicine, Vol.6(5), pp.37-37
DOI: 10.1186/gm554
PMID: 24963352
PMCID: PMC4067994
NLM abbreviation: Genome Med
ISSN: 1756-994X
eISSN: 1756-994X
Publisher: BioMed Central
Language: English
Date published: 2014
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; Iowa Institute of Human Genetics
Record Identifier: 9984007161902771

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