Targeted genomic capture and massively parallel sequencing to identify novel variants causing Chinese hereditary hearing loss
| Autor: | Zhibin Chen, Qinjun Wei, Guangqian Xing, Hongmei Zhu, Yajie Lu, Xin Cao, Jun Yao, Xuli Qian |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Exome sequencing Hearing loss Gene mutation medicine.disease_cause General Biochemistry Genetics and Molecular Biology Connexins otorhinolaryngologic diseases Ethnicity Medicine Humans Gene Medicine(all) Genetics Mutation Massive parallel sequencing Targeted genomic capture Biochemistry Genetics and Molecular Biology(all) business.industry Genetic heterogeneity Genome Human Research General Medicine Pedigree Connexin 26 Human genome Female medicine.symptom business Sequence Analysis |
| Zdroj: | Journal of Translational Medicine |
| ISSN: | 1479-5876 |
| Popis: | Background Hereditary hearing loss is genetically heterogeneous, and hundreds of mutations in than 60 genes are involved in this disease. Therefore, it is difficult to identify the causative gene mutations involved. In this study, we combined targeted genomic capture and massively parallel sequencing (MPS) to address this issue. Methods Using targeted genomic capture and MPS, 104 genes and three microRNA regions were selected and simultaneously sequenced in 23 unrelated probands of Chinese families with nonsyndromic hearing loss. The results were validated by Sanger sequencing for all available members of the probands’ families. To analyze the possible pathogenic functional effects of the variants, three types of prediction programs (Mutation Taster, PROVEAN and SIFT) were used. A total of 195 healthy Chinese Han individuals were compared as controls to verify the novel causative mutations. Results Of the 23 probands, six had mutations in DFNA genes [WFS1 (n = 2), COCH, ACTG1, TMC1, and POU4F3] known to cause autosomal dominant nonsyndromic hearing loss. These included one novel in-frame indel mutation, three novel missense mutations and two reported missense mutations. Furthermore, one proband from a family with recessive DFNB carried two monoallelic mutations in the GJB2 and USH2A genes. All of these mutations co-segregated with the hearing loss phenotype in 36 affected individuals from 7 families and were predicted to be pathogenic. Conclusions Mutations in uncommon deafness genes contribute to a portion of nonsyndromic deafness cases. In the future, critical gene mutations may be accurately and quickly identified in families with hereditary hearing loss by targeted genomic capture and MPS. Electronic supplementary material The online version of this article (doi:10.1186/s12967-014-0311-1) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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