Novel Mutations and Mutation Combinations of TMPRSS3 Cause Various Phenotypes in One Chinese Family with Autosomal Recessive Hearing Impairment

• Type of Material: Article
• Authors: Xue Gao, The General Hospital of the PLA Rocket Force; Yong-yi Yuan, PLA General Hospital; Guo-Jian Wang, PLA General Hospital; Jin-Cao Xu, The General Hospital of the PLA Rocket Force; Yu Su, PLA General Hospital; Xi Lin, Emory University; Pu Dai, PLA General Hospital
• Language: English
• Date: 2017-01-29
• Publisher: Hindawi Publishing Corporation
• Publication Version: Final Published Version
• Copyright Statement: © 2017 Xue Gao et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1155/2017/4707315
• Title of Journal or Parent Work: BioMed Research International
• ISSN: 2314-6133
• Volume: 2017
• Start Page: 1
• End Page: 8
• Grant/Funding Information: These investigations were supported by National Key Research and Development Project (2016YFC1000700, 2016YFC1000704) and National Natural Science Foundation of China (81230020, 81371096) to Pu Dai; grants from National Natural Science Foundation of China (81570929) to Xue Gao; grants from National Natural Science Foundation of China (81371098) and National Key Research and Development Project (2016YFC1000706) to Yong-Yi Yuan; grants from the US National Institute on Deafness and other Communication Disorders (NIDCD R01DC010204, RO1 DC006483, and 4R33DC010476) to Xi Lin; grants from National Natural Science Foundation of China (81360159) and National Basic Research Program of China (2014CB541706) to Guo-Jian Wang; grants from Military Health Care Special Project (15BJZ23) to Jin-Cao Xu; grants from National Natural Science Foundation of China (81400471) to Yu Su.
• Research Categories: Health Sciences, Medicine and Surgery

Abstract

Autosomal recessive hearing impairment with postlingual onset is rare. Exceptions are caused by mutations in the TMPRSS3 gene, which can lead to prelingual (DFNB10) as well as postlingual deafness (DFNB8). TMPRSS3 mutations can be classified as mild or severe, and the phenotype is dependent on the combination of TMPRSS3 mutations. The combination of two severe mutations leads to profound hearing impairment with a prelingual onset, whereas severe mutations in combination with milder TMPRSS3 mutations lead to a milder phenotype with postlingual onset. We characterized a Chinese family (number FH1523) with not only prelingual but also postlingual hearing impairment. Three mutations in TMPRSS3, one novel mutation c.36delC [p.(Phe13Serfs⁎12)], and two previously reported pathogenic mutations, c.916G>A (p.Ala306Thr) and c.316C>T (p.Arg106Cys), were identified. Compound heterozygous mutations of p.(Phe13Serfs⁎12) and p.Ala306Thr manifest as prelingual, profound hearing impairment in the patient (IV: 1), whereas the combination of p.Arg106Cys and p.Ala306Thr manifests as postlingual, milder hearing impairment in the patient (II: 2, II: 3, II: 5), suggesting that p.Arg106Cys mutation has a milder effect than p.(Phe13Serfs⁎12). We concluded that different combinations of TMPRSS3 mutations led to different hearing impairment phenotypes (DFNB8/DFNB10) in this family.