title: Detection and Confirmation of Deafness-Causing Copy Number Variations in the STRC Gene by Massively Parallel Sequencing and Comparative Genomic Hybridization.
abstract: OBJECTIVE
  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.
  
  
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Moteki
authors.affiliation: Molecular Otolaryngology & Renal Research Laboratories, Department of Otolaryngology-Head and Neck Surgery, University of Iowa Hospital and Clinics, Iowa, USA.
authors.forename: Hela
authors.initials: H
authors.lastname: Azaiez
authors.affiliation: Molecular Otolaryngology & Renal Research Laboratories, Department of Otolaryngology-Head and Neck Surgery, University of Iowa Hospital and Clinics, Iowa, USA.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Sloan-Heggen
authors.affiliation: Molecular Otolaryngology & Renal Research Laboratories, Department of Otolaryngology-Head and Neck Surgery, University of Iowa Hospital and Clinics, Iowa, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Booth
authors.affiliation: Department of Otorhinolaryngology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Shin-Ya
authors.initials: SY
authors.lastname: Nishio
authors.affiliation: Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Wakui
authors.affiliation: Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Yamaguchi
authors.affiliation: Molecular Otolaryngology & Renal Research Laboratories, Department of Otolaryngology-Head and Neck Surgery, University of Iowa Hospital and Clinics, Iowa, USA.
authors.forename: Diana L
authors.initials: DL
authors.lastname: Kolbe
authors.affiliation: Department of Otorhinolaryngology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Yoh-Ichiro
authors.initials: YI
authors.lastname: Iwasa
authors.affiliation: Molecular Otolaryngology & Renal Research Laboratories, Department of Otolaryngology-Head and Neck Surgery, University of Iowa Hospital and Clinics, Iowa, USA.
authors.forename: A Eliot
authors.initials: AE
authors.lastname: Shearer
authors.affiliation: Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Fukushima
authors.affiliation: Molecular Otolaryngology & Renal Research Laboratories, Department of Otolaryngology-Head and Neck Surgery, University of Iowa Hospital and Clinics, Iowa, USA.
authors.forename: Richard J H
authors.initials: RJ
authors.lastname: Smith
authors.affiliation: Department of Otorhinolaryngology, Shinshu University School of Medicine, Matsumoto, Japan usami@shinshu-u.ac.jp.
authors.forename: Shin-Ichi
authors.initials: SI
authors.lastname: Usami
mesh_terms: D000328:Adult; D002648:Child; D055028:Comparative Genomic Hybridization / Q000379:methods; D056915:DNA Copy Number Variations; D003638:Deafness / Q000235:genetics*; D005260:Female; D005820:Genetic Testing / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C499079:STRC protein, human
keywords: STRC; array CHG; copy number variations; hearing loss; massively parallel sequencing