title: Identifying Children With Poor Cochlear Implantation Outcomes Using Massively Parallel Sequencing.
abstract: Cochlear implantation is currently the treatment of choice for children with severe to profound hearing impairment. However, the outcomes with cochlear implants (CIs) vary significantly among recipients. The purpose of the present study is to identify the genetic determinants of poor CI outcomes. Twelve children with poor CI outcomes (the "cases") and 30 "matched controls" with good CI outcomes were subjected to comprehensive genetic analyses using massively parallel sequencing, which targeted 129 known deafness genes. Audiological features, imaging findings, and auditory/speech performance with CIs were then correlated to the genetic diagnoses. We identified genetic variants which are associated with poor CI outcomes in 7 (58%) of the 12 cases; 4 cases had bi-allelic PCDH15 pathogenic mutations and 3 cases were homozygous for the DFNB59 p.G292R variant. Mutations in the WFS1, GJB3, ESRRB, LRTOMT, MYO3A, and POU3F4 genes were detected in 7 (23%) of the 30 matched controls. The allele frequencies of PCDH15 and DFNB59 variants were significantly higher in the cases than in the matched controls (both P < 0.001). In the 7 CI recipients with PCDH15 or DFNB59 variants, otoacoustic emissions were absent in both ears, and imaging findings were normal in all 7 implanted ears. PCDH15 or DFNB59 variants are associated with poor CI performance, yet children with PCDH15 or DFNB59 variants might show clinical features indistinguishable from those of other typical pediatric CI recipients. Accordingly, genetic examination is indicated in all CI candidates before operation.
authors.affiliation: From Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan (C-CW, Y-HL, T-CL, K-NL, C-JH); Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan (C-CW, W-SY, P-LC); Graduate Institute of Medical Genomics and Proteomics, National Taiwan University College of Medicine, Taipei, Taiwan (Y-HL, P-LC); Department of Otolaryngology, Cardinal Tien Hospital, New Taipei, Taiwan (K-NL); Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan (W-SY, P-LC); Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan (W-SY, P-LC); Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan (W-SY, P-LC); Department of Otolaryngology, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan (C-JH); and Department of Otolaryngology, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan (C-MW).
authors.forename: Chen-Chi
authors.initials: CC
authors.lastname: Wu
authors.forename: Yin-Hung
authors.initials: YH
authors.lastname: Lin
authors.forename: Tien-Chen
authors.initials: TC
authors.lastname: Liu
authors.forename: Kai-Nan
authors.initials: KN
authors.lastname: Lin
authors.forename: Wei-Shiung
authors.initials: WS
authors.lastname: Yang
authors.forename: Chuan-Jen
authors.initials: CJ
authors.lastname: Hsu
authors.forename: Pei-Lung
authors.initials: PL
authors.lastname: Chen
authors.forename: Che-Ming
authors.initials: CM
authors.lastname: Wu
mesh_terms: D001299:Audiometry; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000235:genetics*; D002675:Child, Preschool; D019929:Cochlear Implantation / Q000379:methods*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D034381:Hearing Loss / Q000235:genetics* / Q000601:surgery*; D006319:Hearing Loss, Sensorineural / Q000235:genetics / Q000601:surgery; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D013060:Speech; D016896:Treatment Outcome; D000094524:Gasdermins
chemical_list: D000070585:Cadherin Related Proteins; D015820:Cadherins; D009419:Nerve Tissue Proteins; C498835:CDHR15, human; C519847:PJVK protein, human; D000094524:Gasdermins