Comprehensive genetic testing in the clinical evaluation of 1119 patients with hearing loss

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Web End = Hum Genet (2016) 135:441450 DOI 10.1007/s00439-016-1648-8

ORIGINAL INVESTIGATION

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Web End = Comprehensive genetic testing in the clinical evaluation of 1119 patients with hearing loss

Abstract Hearing loss is the most common sensory decit 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 identication of the underlying genetic cause for hearing loss in 440 patients (39 %). Pathogenic variants were found in 49 genes and included mis-sense 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

A. O. Bierer, A. E. Shearer, and D. L. Kolbe all contributed equally to this work.

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* Richard J. H. Smith [email protected]

1 Molecular Otolaryngology and Renal Research Laboratories, Department of OtolaryngologyHead and Neck Surgery, University of Iowa Carver College of Medicine, 200 Hawkins Drive, Iowa City, IA 52242, USA

2 Department of Molecular Physiology and Biophysics, University of Iowa Carver College of Medicine, Iowa City 52242, IA, USA

3 Interdepartmental PhD Program in Genetics, University of Iowa, Iowa City 52242, IA, USA

Christina M. SloanHeggen1,2 Amanda O. Bierer1 A. Eliot Shearer1

Diana L. Kolbe1 Carla J. Nishimura1 Kathy L. Frees1 Sean S. Ephraim1 Seiji B. Shibata1 Kevin T. Booth1 Colleen A. Campbell1 Paul T. Ranum1 Amy E. Weaver1 E. Ann BlackZiegelbein1 Donghong Wang1 Hela Azaiez1 Richard J. H. Smith1,2,3

Received: 16 December 2015 / Accepted: 14 February 2016 / Published online: 11 March 2016 The Author(s) 2016. This article is published with open access at Springerlink.com

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