Detection and Confirmation of Deafness-Causing Copy Number Variations in the STRC Gene by Massively Parallel Sequencing and Comparative Genomic Hybridization

Hideaki Moteki; Hela Azaiez; Christina M Sloan-Heggen; Kevin Booth; Shin-Ya Nishio; Keiko Wakui; Tomomi Yamaguchi; Diana L Kolbe; Yoh-Ichiro Iwasa; A Eliot Shearer; Yoshimitsu Fukushima; Richard J H Smith; Shin-Ichi Usami

doi:10.1177/0003489416661345

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Detection and Confirmation of Deafness-Causing Copy Number Variations in the STRC Gene by Massively Parallel Sequencing and Comparative Genomic Hybridization

Journal article

Peer reviewed

Detection and Confirmation of Deafness-Causing Copy Number Variations in the STRC Gene by Massively Parallel Sequencing and Comparative Genomic Hybridization

Hideaki Moteki, Hela Azaiez, Christina M Sloan-Heggen, Kevin Booth, Shin-Ya Nishio, Keiko Wakui, Tomomi Yamaguchi, Diana L Kolbe, Yoh-Ichiro Iwasa, A Eliot Shearer, …

Annals of otology, rhinology & laryngology, Vol.125(11), pp.918-923

11/2016

DOI: 10.1177/0003489416661345

PMCID: PMC5537730

PMID: 27469136

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Abstract

Copy number variations (CNVs), a major cause of genetic hearing loss, most frequently involve the STRC gene, located on chr15q15.3 and causally related to autosomal recessive non-syndromic hearing loss (ARNSHL) at the DFNB16 locus. The interpretation of STRC sequence data can be challenging due to the existence of a virtually identical pseudogene, pSTRC, that promotes complex genomic rearrangements in this genomic region. Targeted genomic enrichment with massively parallel sequencing (TGE+MPS) has emerged as the preferred method by which to provide comprehensive genetic testing for hearing loss. We aimed to identify CNVs in the STRC region using established and validated bioinformatics methods. We used TGE+MPS to identify the genetic cause of hearing loss. The CNV results were confirmed with customized array comparative genomic hybridization (array CGH). Three probands with progressive mild to moderate hearing loss were found among 40 subjects with ARNSHL to segregate homozygous STRC deletions and gene to pseudogene conversion. Array CGH showed that the deletions/conversions span multiple genes outside of the exons captured by TGE+MPS. These data further validate the necessity to integrate the detection of both simple variant changes and complex genomic rearrangements in the clinical diagnosis of genetic hearing loss.

Deafness - genetics

Membrane Proteins - genetics

Humans

Adult

Female

Male

Comparative Genomic Hybridization - methods

High-Throughput Nucleotide Sequencing - methods

Child

Genetic Testing - methods

DNA Copy Number Variations

Details

Title: Subtitle: Detection and Confirmation of Deafness-Causing Copy Number Variations in the STRC Gene by Massively Parallel Sequencing and Comparative Genomic Hybridization
Creators: Hideaki Moteki - Department of Otorhinolaryngology, Shinshu University School of Medicine, Matsumoto, Japan Molecular Otolaryngology & Renal Research Laboratories, Department of Otolaryngology-Head and Neck Surgery, University of Iowa Hospital and Clinics, Iowa, USA
Hela Azaiez - Molecular Otolaryngology & Renal Research Laboratories, Department of Otolaryngology-Head and Neck Surgery, University of Iowa Hospital and Clinics, Iowa, USA
Christina M Sloan-Heggen - Molecular Otolaryngology & Renal Research Laboratories, Department of Otolaryngology-Head and Neck Surgery, University of Iowa Hospital and Clinics, Iowa, USA
Kevin Booth - Molecular Otolaryngology & Renal Research Laboratories, Department of Otolaryngology-Head and Neck Surgery, University of Iowa Hospital and Clinics, Iowa, USA
Shin-Ya Nishio - Department of Otorhinolaryngology, Shinshu University School of Medicine, Matsumoto, Japan
Keiko Wakui - Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto, Japan
Tomomi Yamaguchi - Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto, Japan
Diana L Kolbe - Molecular Otolaryngology & Renal Research Laboratories, Department of Otolaryngology-Head and Neck Surgery, University of Iowa Hospital and Clinics, Iowa, USA
Yoh-Ichiro Iwasa - Department of Otorhinolaryngology, Shinshu University School of Medicine, Matsumoto, Japan
A Eliot Shearer - Molecular Otolaryngology & Renal Research Laboratories, Department of Otolaryngology-Head and Neck Surgery, University of Iowa Hospital and Clinics, Iowa, USA
Yoshimitsu Fukushima - Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto, Japan
Richard J H Smith - Molecular Otolaryngology & Renal Research Laboratories, Department of Otolaryngology-Head and Neck Surgery, University of Iowa Hospital and Clinics, Iowa, USA
Shin-Ichi Usami - Department of Otorhinolaryngology, Shinshu University School of Medicine, Matsumoto, Japan usami@shinshu-u.ac.jp
Resource Type: Journal article
Publication Details: Annals of otology, rhinology & laryngology, Vol.125(11), pp.918-923
DOI: 10.1177/0003489416661345
PMID: 27469136
PMCID: PMC5537730
NLM abbreviation: Ann Otol Rhinol Laryngol
ISSN: 0003-4894
eISSN: 1943-572X
Publisher: SAGE Publications; United States
Grant note: R01 DC003544 / NIDCD NIH HHS R01 DC012049 / NIDCD NIH HHS R01 DC002842 / NIDCD NIH HHS T32 GM007337 / NIGMS NIH HHS
Language: English
Date published: 11/2016
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; Otolaryngology; Internal Medicine; Iowa Institute of Human Genetics
Record Identifier: 9984006348702771

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