Dataset Information

Identification of a complex genomic rearrangement in TMPRSS3 by massively parallel sequencing in Chinese cases with prelingual hearing loss.

ABSTRACT: 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.

SUBMITTER: Li X

PROVIDER: S-EPMC6565588 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Identification of a complex genomic rearrangement in TMPRSS3 by massively parallel sequencing in Chinese cases with prelingual hearing loss.

Li Xinlei X Tan Bo B Wang Xiaoqian X Xu Xiaofei X Wang Cuicui C Zhong Mingjun M Zhao Qiuling Q Bao Zhongwei Z Peng Weihua W Zhang Lei L Cheng Jing J Lu Yu Y Wu Peina P Yuan Huijun H

Molecular genetics & genomic medicine 20190423 6

<h4>Background</h4>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.<h4>Methods</h4>We applied targeted genomic enrichment and massively parallel sequencing to screen 110 genes associated with nonsyndromic HL i ...[more]

PMID: 31016883

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Project description:A variant in a transcription factor gene, POU4F3, is responsible for autosomal dominant nonsyndromic hereditary hearing loss, DFNA15. To date, 14 variants, including a whole deletion of POU4F3, have been reported to cause HL in various ethnic groups. In the present study, genetic screening for POU4F3 variants was carried out for a large series of Japanese hearing loss (HL) patients to clarify the prevalence and clinical characteristics of DFNA15 in the Japanese population. Massively parallel DNA sequencing of 68 target candidate genes was utilized in 2,549 unrelated Japanese HL patients (probands) to identify genomic variations responsible for HL. The detailed clinical features in patients with POU4F3 variants were collected from medical charts and analyzed. Novel 12 POU4F3 likely pathogenic variants (six missense variants, three frameshift variants, and three nonsense variants) were successfully identified in 15 probands (2.5%) among 602 families exhibiting autosomal dominant HL, whereas no variants were detected in the other 1,947 probands with autosomal recessive or inheritance pattern unknown HL. To obtain the audiovestibular configuration of the patients harboring POU4F3 variants, we collected audiograms and vestibular symptoms of the probands and their affected family members. Audiovestibular phenotypes in a total of 24 individuals from the 15 families possessing variants were characterized by progressive HL, with a large variation in the onset age and severity with or without vestibular symptoms observed. Pure-tone audiograms indicated the most prevalent configuration as mid-frequency HL type followed by high-frequency HL type, with asymmetry observed in approximately 20% of affected individuals. Analysis of the relationship between age and pure-tone average suggested that individuals with truncating variants showed earlier onset and slower progression of HL than did those with non-truncating variants. The present study showed that variants in POU4F3 were a common cause of autosomal dominant HL.

Dataset Information

Identification of a complex genomic rearrangement in TMPRSS3 by massively parallel sequencing in Chinese cases with prelingual hearing loss.

Publications

Identification of a complex genomic rearrangement in TMPRSS3 by massively parallel sequencing in Chinese cases with prelingual hearing loss.

Similar Datasets

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