Journal article
Comprehensive genetic testing in the clinical evaluation of 1119 patients with hearing loss
Human genetics, Vol.135(4), pp.441-450
04/2016
DOI: 10.1007/s00439-016-1648-8
PMCID: PMC4796320
PMID: 26969326
Abstract
Hearing loss is the most common sensory deficit in humans, affecting 1 in 500 newborns. Due to its genetic heterogeneity, comprehensive diagnostic testing has not previously been completed in a large multiethnic cohort. To determine the aggregate contribution inheritance makes to non-syndromic hearing loss, we performed comprehensive clinical genetic testing with targeted genomic enrichment and massively parallel sequencing on 1119 sequentially accrued patients. No patient was excluded based on phenotype, inheritance or previous testing. Testing resulted in identification of the underlying genetic cause for hearing loss in 440 patients (39%). Pathogenic variants were found in 49 genes and included missense variants (49%), large copy number changes (18%), small insertions and deletions (18%), nonsense variants (8%), splice-site alterations (6%), and promoter variants (<1%). The diagnostic rate varied considerably based on phenotype and was highest for patients with a positive family history of hearing loss or when the loss was congenital and symmetric. The spectrum of implicated genes showed wide ethnic variability. These findings support the more efficient utilization of medical resources through the development of evidence-based algorithms for the diagnosis of hearing loss.
Details
- Title: Subtitle
- Comprehensive genetic testing in the clinical evaluation of 1119 patients with hearing loss
- Creators
- Christina M Sloan-Heggen - Department of Molecular Physiology and Biophysics, University of Iowa Carver College of Medicine, Iowa City, 52242, IA, USAAmanda O Bierer - Molecular Otolaryngology and Renal Research Laboratories, Department of Otolaryngology-Head and Neck Surgery, University of Iowa Carver College of Medicine, 200 Hawkins Drive, Iowa City, IA, 52242, USAA Eliot Shearer - Molecular Otolaryngology and Renal Research Laboratories, Department of Otolaryngology-Head and Neck Surgery, University of Iowa Carver College of Medicine, 200 Hawkins Drive, Iowa City, IA, 52242, USADiana L Kolbe - Molecular Otolaryngology and Renal Research Laboratories, Department of Otolaryngology-Head and Neck Surgery, University of Iowa Carver College of Medicine, 200 Hawkins Drive, Iowa City, IA, 52242, USACarla J Nishimura - Molecular Otolaryngology and Renal Research Laboratories, Department of Otolaryngology-Head and Neck Surgery, University of Iowa Carver College of Medicine, 200 Hawkins Drive, Iowa City, IA, 52242, USAKathy L Frees - Molecular Otolaryngology and Renal Research Laboratories, Department of Otolaryngology-Head and Neck Surgery, University of Iowa Carver College of Medicine, 200 Hawkins Drive, Iowa City, IA, 52242, USASean S Ephraim - Molecular Otolaryngology and Renal Research Laboratories, Department of Otolaryngology-Head and Neck Surgery, University of Iowa Carver College of Medicine, 200 Hawkins Drive, Iowa City, IA, 52242, USASeiji B Shibata - Molecular Otolaryngology and Renal Research Laboratories, Department of Otolaryngology-Head and Neck Surgery, University of Iowa Carver College of Medicine, 200 Hawkins Drive, Iowa City, IA, 52242, USAKevin T Booth - Molecular Otolaryngology and Renal Research Laboratories, Department of Otolaryngology-Head and Neck Surgery, University of Iowa Carver College of Medicine, 200 Hawkins Drive, Iowa City, IA, 52242, USAColleen A Campbell - Molecular Otolaryngology and Renal Research Laboratories, Department of Otolaryngology-Head and Neck Surgery, University of Iowa Carver College of Medicine, 200 Hawkins Drive, Iowa City, IA, 52242, USAPaul T Ranum - Molecular Otolaryngology and Renal Research Laboratories, Department of Otolaryngology-Head and Neck Surgery, University of Iowa Carver College of Medicine, 200 Hawkins Drive, Iowa City, IA, 52242, USAAmy E Weaver - Molecular Otolaryngology and Renal Research Laboratories, Department of Otolaryngology-Head and Neck Surgery, University of Iowa Carver College of Medicine, 200 Hawkins Drive, Iowa City, IA, 52242, USAE Ann Black-Ziegelbein - Molecular Otolaryngology and Renal Research Laboratories, Department of Otolaryngology-Head and Neck Surgery, University of Iowa Carver College of Medicine, 200 Hawkins Drive, Iowa City, IA, 52242, USADonghong Wang - Molecular Otolaryngology and Renal Research Laboratories, Department of Otolaryngology-Head and Neck Surgery, University of Iowa Carver College of Medicine, 200 Hawkins Drive, Iowa City, IA, 52242, USAHela Azaiez - Molecular Otolaryngology and Renal Research Laboratories, Department of Otolaryngology-Head and Neck Surgery, University of Iowa Carver College of Medicine, 200 Hawkins Drive, Iowa City, IA, 52242, USARichard J H Smith - Interdepartmental PhD Program in Genetics, University of Iowa, Iowa City, 52242, IA, USA. richard-smith@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- Human genetics, Vol.135(4), pp.441-450
- DOI
- 10.1007/s00439-016-1648-8
- PMID
- 26969326
- PMCID
- PMC4796320
- NLM abbreviation
- Hum Genet
- ISSN
- 1432-1203
- eISSN
- 1432-1203
- Publisher
- Germany
- Grant note
- DC002842 / NIDCD NIH HHS DC012049 / NIDCD NIH HHS NIDCD RO1S DC003544 / PHS HHS R01 DC012049 / NIDCD NIH HHS R01 DC002842 / NIDCD NIH HHS T32 GM007337 / NIGMS NIH HHS
- Language
- English
- Date published
- 04/2016
- 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; Cardiovascular Medicine; Otolaryngology; Internal Medicine; Iowa Institute of Human Genetics
- Record Identifier
- 9984007292102771
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