Identification of CDH23 mutations in Korean families with hearing loss by whole-exome sequencing

BMC Medical Genetics

Soo Kyung Koo³  Won Gi Yoo¹  Joong-Wook Shin²  Bo-Young Kim³  Mi-Hyun Park³  Hong-Joon Park²  Hae-Mi Woo³ 

[1] Division of Malaria and Parasitic Diseases, Center for Immunology and Pathology, National Institute of Health, Chungcheongbuk-do South Korea;Soree Ear Clinic, Seoul, South Korea;Division of Intractable Diseases, Center for Biomedical Sciences, National Institute of Health, Chungcheongbuk-do 363-951, South Korea

关键词: Whole-exome sequencing;    Mutation;    CDH23;    Hearing loss;   

Others  :  1092049
DOI  :  10.1186/1471-2350-15-46

 received in 2013-12-23, accepted in 2014-04-22,  发布年份 2014

【 摘 要 】

Background

Patient genetic heterogeneity renders it difficult to discover disease-cause genes. Whole-exome sequencing is a powerful new strategy that can be used to this end. The purpose of the present study was to identify a hitherto unknown mutation causing autosomal recessive nonsyndromic hearing loss (ARNSHL) in Korean families.

Methods

We performed whole-exome sequencing in 16 individuals from 13 unrelated small families with ARNSHL. After filtering out population-specific polymorphisms, we focused on known deafness genes. Pathogenic effects of the detected mutations on protein structure or function were predicted via in silico analysis.

Results

We identified compound heterozygous CDH23 mutations in hearing-loss genes of two families. These include two previously reported pathological mutations, p.Pro240Leu and p.Glu1595Lys, as well as one novel mutation, p.Asn342Ser. The p.Pro240Leu mutation was found in both families. We also identified 26 non-synonymous variants in CDH23 coding exons from 16 hearing-loss patients and 30 Korean exomes.

Conclusion

The present study is the first to show that CDH23 mutations cause hearing loss in Koreans. Although the precise contribution made by such mutations needs to be determined using a larger patient cohort, our data indicate that mutations in the CDH23 gene are one of the most important causes of non-syndromic hearing loss in East Asians. Further exome sequencing will identify common mutations or polymorphisms and contribute to the molecular diagnosis of, and development of new therapies for, hereditary hearing loss.

【 授权许可】

   
2014 Woo et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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