Frontiers in Genetics (Jul 2019)
Proband Whole-Exome Sequencing Identified Genes Responsible for Autosomal Recessive Non-Syndromic Hearing Loss in 33 Chinese Nuclear Families
- Shushan Sang,
- Shushan Sang,
- Jie Ling,
- Jie Ling,
- Jie Ling,
- Xuezhong Liu,
- Xuezhong Liu,
- Xuezhong Liu,
- Lingyun Mei,
- Lingyun Mei,
- Xinzhang Cai,
- Xinzhang Cai,
- Taoxi Li,
- Taoxi Li,
- Taoxi Li,
- Wu Li,
- Wu Li,
- Meng Li,
- Meng Li,
- Jie Wen,
- Jie Wen,
- Xianlin Liu,
- Xianlin Liu,
- Jing Liu,
- Jing Liu,
- Yalan Liu,
- Yalan Liu,
- Hongsheng Chen,
- Hongsheng Chen,
- Chufeng He,
- Chufeng He,
- Yong Feng,
- Yong Feng,
- Yong Feng,
- Yong Feng
Affiliations
- Shushan Sang
- Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha, China
- Shushan Sang
- Key Laboratory of Otolaryngology Major Diseases Research of Hunan Province, Changsha, China
- Jie Ling
- Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha, China
- Jie Ling
- Institute of Molecular Precision Medicine, Xiangya Hospital, Central South University, Changsha, China
- Jie Ling
- Hunan Key Laboratory of Molecular Precision Medicine, Changsha, China
- Xuezhong Liu
- Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha, China
- Xuezhong Liu
- Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL, United States
- Xuezhong Liu
- Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, United States
- Lingyun Mei
- Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha, China
- Lingyun Mei
- Key Laboratory of Otolaryngology Major Diseases Research of Hunan Province, Changsha, China
- Xinzhang Cai
- Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha, China
- Xinzhang Cai
- Key Laboratory of Otolaryngology Major Diseases Research of Hunan Province, Changsha, China
- Taoxi Li
- Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha, China
- Taoxi Li
- Key Laboratory of Otolaryngology Major Diseases Research of Hunan Province, Changsha, China
- Taoxi Li
- Hunan Jiahui Genetics Hospital, Changsha, China
- Wu Li
- Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha, China
- Wu Li
- Key Laboratory of Otolaryngology Major Diseases Research of Hunan Province, Changsha, China
- Meng Li
- Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha, China
- Meng Li
- Key Laboratory of Otolaryngology Major Diseases Research of Hunan Province, Changsha, China
- Jie Wen
- Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha, China
- Jie Wen
- Key Laboratory of Otolaryngology Major Diseases Research of Hunan Province, Changsha, China
- Xianlin Liu
- Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha, China
- Xianlin Liu
- Key Laboratory of Otolaryngology Major Diseases Research of Hunan Province, Changsha, China
- Jing Liu
- Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha, China
- Jing Liu
- Key Laboratory of Otolaryngology Major Diseases Research of Hunan Province, Changsha, China
- Yalan Liu
- Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha, China
- Yalan Liu
- Key Laboratory of Otolaryngology Major Diseases Research of Hunan Province, Changsha, China
- Hongsheng Chen
- Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha, China
- Hongsheng Chen
- Key Laboratory of Otolaryngology Major Diseases Research of Hunan Province, Changsha, China
- Chufeng He
- Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha, China
- Chufeng He
- Key Laboratory of Otolaryngology Major Diseases Research of Hunan Province, Changsha, China
- Yong Feng
- Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha, China
- Yong Feng
- Key Laboratory of Otolaryngology Major Diseases Research of Hunan Province, Changsha, China
- Yong Feng
- Hunan Jiahui Genetics Hospital, Changsha, China
- Yong Feng
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- DOI
- https://doi.org/10.3389/fgene.2019.00639
- Journal volume & issue
-
Vol. 10
Abstract
Autosomal recessive non-syndromic hearing loss (ARNSHL) is a highly heterogeneous disease involving more than 70 pathogenic genes. However, most ARNSHL families have small-sized pedigrees with limited genetic information, rendering challenges for the molecular diagnosis of these patients. Therefore, we attempted to establish a strategy for identifying deleterious variants associated with ARNSHL by applying proband whole-exome sequencing (proband-WES). Aside from desiring to improve molecular diagnostic rates, we also aimed to search for novel deafness genes shared by patients with similar phenotype, making up for the deficiency of small ARNSHL families. In this study, 48.5% (16/33) families were detected the pathogenic variants in eight known deafness genes, including 10 novel variants identified in TMPRSS3 (MIM 605551), MYO15A (MIM 602666), TMC1 (MIM 606706), ADGRV1 (MIM 602851), and PTPRQ (MIM 603317). Apart from six novel variants with a truncating effect (nonsense, deletion, insertion, and splice-site), four novel missense variants were not found in 200 unrelated control population by using Sanger sequencing. It is important to note that none of novel genes were shared across different pedigrees, indicating that a larger sample size might be needed. Proband-WES is a cost-effective and precise way of identifying causative variants in nuclear families with ARNSHL. This economical strategy may be appropriated as a clinical application to provide molecular diagnostics, genetic counseling, and individualized health maintenance measures for patients with ARNSHL at hearing clinics.
Keywords
