Open AccessIdentification of a complex genomic rearrangement in TMPRSS3 by massively parallel sequencing in Chinese cases with prelingual hearing loss
Author(s) -
Li Xinlei,
Tan Bo,
Wang Xiaoqian,
Xu Xiaofei,
Wang Cuicui,
Zhong Mingjun,
Zhao Qiuling,
Bao Zhongwei,
Peng Weihua,
Zhang Lei,
Cheng Jing,
Lu Yu,
Wu Peina,
Yuan Huijun
Publication year - 2019
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.685
Subject(s) - genetics , massive parallel sequencing , biology , missense mutation , copy number variation , exon , hearing loss , dna sequencing , mutation , gene , genome , medicine , audiology
Background Genetic variants in TMPRSS3 have been causally linked to autosomal recessive nonsyndromic hearing loss (HL) at the DFNB8 and DFNB10 loci. These variants include both single nucleotide and copy number variations (CNVs). In this study, we aim to identify the genetic cause in three Chinese subjects with prelingual profound sensorineural HL. Methods We applied targeted genomic enrichment and massively parallel sequencing to screen 110 genes associated with nonsyndromic HL in the three affected subjects. CNVplex ® analysis and polymerase chain reaction (PCR) were performed for CNV detection. Results We identified biallelic variations in TMPRSS3 including a novel complex genomic rearrangement and a novel missense mutation, c.551T>C. We have mapped the breakpoints of the genomic rearrangement and showed that it consisted of two deletions and an inversion encompassing exon 3 to exon 9 of TMPRSS3 . Conclusion Our study expanded the mutational spectrum of TMPRSS3 to include complex genomic rearrangements. It showcased the importance of an integrative approach to investigate CNVs and their contribution to HL.