title: Whole-exome sequencing to decipher the genetic heterogeneity of hearing loss in a Chinese family with deaf by deaf mating.
abstract: Inherited deafness has been shown to have high genetic heterogeneity. For many decades, linkage analysis and candidate gene approaches have been the main tools to elucidate the genetics of hearing loss. However, this associated study design is costly, time-consuming, and unsuitable for small families. This is mainly due to the inadequate numbers of available affected individuals, locus heterogeneity, and assortative mating. Exome sequencing has now become technically feasible and a cost-effective method for detection of disease variants underlying Mendelian disorders due to the recent advances in next-generation sequencing (NGS) technologies. In the present study, we have combined both the Deafness Gene Mutation Detection Array and exome sequencing to identify deafness causative variants in a large Chinese composite family with deaf by deaf mating. The simultaneous screening of the 9 common deafness mutations using the allele-specific PCR based universal array, resulted in the identification of the 1555A>G in the mitochondrial DNA (mtDNA) 12S rRNA in affected individuals in one branch of the family. We then subjected the mutation-negative cases to exome sequencing and identified novel causative variants in the MYH14 and WFS1 genes. This report confirms the effective use of a NGS technique to detect pathogenic mutations in affected individuals who were not candidates for classical genetic studies.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Institute of Otology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China; Departments of Otolaryngology-Head and Neck Surgery, Leonard M. Miller School of Medicine, University of Miami, Miami, Florida, United States of America.
authors.forename: Jie
authors.initials: J
authors.lastname: Qing
authors.affiliation: Departments of Otolaryngology-Head and Neck Surgery, Leonard M. Miller School of Medicine, University of Miami, Miami, Florida, United States of America.
authors.forename: Denise
authors.initials: D
authors.lastname: Yan
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Institute of Otology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Departments of Otolaryngology-Head and Neck Surgery, Leonard M. Miller School of Medicine, University of Miami, Miami, Florida, United States of America.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Institute of Otology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Weijing
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Institute of Otology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Zian
authors.initials: Z
authors.lastname: Xiao
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Institute of Otology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Yuyuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Institute of Otology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Departments of Otolaryngology-Head and Neck Surgery, Leonard M. Miller School of Medicine, University of Miami, Miami, Florida, United States of America.
authors.forename: Lilin
authors.initials: L
authors.lastname: Du
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Institute of Otology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Dinghua
authors.initials: D
authors.lastname: Xie
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Institute of Otology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China; Departments of Otolaryngology-Head and Neck Surgery, Leonard M. Miller School of Medicine, University of Miami, Miami, Florida, United States of America.
authors.forename: Xue Zhong
authors.initials: XZ
authors.lastname: Liu
mesh_terms: D017668:Age of Onset; D000483:Alleles; D000595:Amino Acid Sequence; D044466:Asian People; D002681:China; D017124:Conserved Sequence; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial; D059472:Exome; D005260:Female; D018740:Genetic Heterogeneity; D034381:Hearing Loss / Q000175:diagnosis / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D018995:Myosin Heavy Chains / Q000737:chemistry / Q000235:genetics; D024462:Myosin Type II / Q000737:chemistry / Q000235:genetics; D010375:Pedigree; D012335:RNA, Ribosomal; D016415:Sequence Alignment; D014057:Tomography, X-Ray Computed
chemical_list: D004272:DNA, Mitochondrial; D008565:Membrane Proteins; D018995:Myosin Heavy Chains; D024462:Myosin Type II; D012335:RNA, Ribosomal; C477830:MYH7b protein, human; C075526:RNA, ribosomal, 12S; C114987:wolframin protein