Ling Zong1, Kaitian Chen2, Xuan Wu2, Min Liu2, Hongyan Jiang3. 1. Department of Otorhinolaryngology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, PR China; Department of Otorhinolaryngology, The First Affiliated Hospital, Sun Yat-sen University and Institute of Otorhinolaryngology, Sun Yat-sen University, Guangzhou, 510080, PR China. 2. Department of Otorhinolaryngology, The First Affiliated Hospital, Sun Yat-sen University and Institute of Otorhinolaryngology, Sun Yat-sen University, Guangzhou, 510080, PR China. 3. Department of Otorhinolaryngology, The First Affiliated Hospital, Sun Yat-sen University and Institute of Otorhinolaryngology, Sun Yat-sen University, Guangzhou, 510080, PR China; Department of Otorhinolaryngology, Hainan General Hospital, Haikou, 570311, PR China. Electronic address: jhongy@mail.sysu.edu.cn.
Abstract
OBJECTIVE: Identification of rare deafness genes for inherited congenital sensorineural hearing impairment remains difficult, because a large variety of genes are implicated. In this study we applied targeted capture and next-generation sequencing to uncover the underlying gene in a three-generation Han family segregating recessive inherited hearing loss and retinitis pigmentosa. METHODS: After excluding mutations in common deafness genes GJB2, SLC26A4 and the mitochondrial gene, genomic DNA of the proband of a Han family was subjected to targeted next-generation sequencing. The candidate mutations were confirmed by Sanger sequencing and subsequently analyzed with in silico tools. RESULTS: An unreported splice site mutation c.3924+1G > C compound with c.6028G > A in the MYO7A gene were detected to cosegregate with the phenotype in this pedigree. Both mutations, located in the evolutionarily conserved FERM domain in myosin VIIA, were predicted to be pathogenic. In this family, profound sensorineural hearing impairment and retinitis pigmentosa without vestibular disorder, constituted the typical Usher syndrome type 2. CONCLUSION: Identification of novel mutation in compound heterozygosity in MYO7A gene revealed the genetic origin of Usher syndrome type 2 in this Han family.
OBJECTIVE: Identification of rare deafness genes for inherited congenital sensorineural hearing impairment remains difficult, because a large variety of genes are implicated. In this study we applied targeted capture and next-generation sequencing to uncover the underlying gene in a three-generation Han family segregating recessive inherited hearing loss and retinitis pigmentosa. METHODS: After excluding mutations in common deafness genes GJB2, SLC26A4 and the mitochondrial gene, genomic DNA of the proband of a Han family was subjected to targeted next-generation sequencing. The candidate mutations were confirmed by Sanger sequencing and subsequently analyzed with in silico tools. RESULTS: An unreported splice site mutation c.3924+1G > C compound with c.6028G > A in the MYO7A gene were detected to cosegregate with the phenotype in this pedigree. Both mutations, located in the evolutionarily conserved FERM domain in myosin VIIA, were predicted to be pathogenic. In this family, profound sensorineural hearing impairment and retinitis pigmentosa without vestibular disorder, constituted the typical Usher syndrome type 2. CONCLUSION: Identification of novel mutation in compound heterozygosity in MYO7A gene revealed the genetic origin of Usher syndrome type 2 in this Han family.