BMC Medical Genetics, 2013, 01, 72─79

Whole-exome sequencing identifies MYO15A mutations as a cause of autosomal recessive nonsyndromic hearing loss in Korean families

Hae-Mi Woo, Hong-Joon Park, Jeong-In Baek, Mi-Hyun Park, Un-Kyung Kim, Borum Sagong, Soo Kyung Koo

Abstract

Background: The genetic heterogeneity of hearing loss makes genetic diagnosis expensive and time consuming using available methods. Whole-exome sequencing has recently been introduced as an alternative approach to identifying causative mutations in Mendelian disorders.
Methods: To identify the hidden mutations that cause autosomal recessive nonsyndromic hearing loss (ARNSHL), we performed whole-exome sequencing of 13 unrelated Korean small families with ARNSHL who were negative for GJB2 or SLC26A4 mutations.
Results: We found two novel compound heterozygous mutations, IVS11 + 1 and p.R2146Q, of MYO15A in one (SR903 family) of the 13 families with ARNSHL. In addition to these causative mutations, 13 nonsynonymous variants, including variants with uncertain pathogenicity (SR285 family), were identified in the coding exons of MYO15A from Korean exomes.
Conclusion: This is the first report of MYO15A mutations in an East Asian population. We suggest that close attention should be paid to this gene when performing genetic testing of patients with hearing loss in East Asia. The present results also indicate that whole-exome sequencing is a valuable method for comprehensive medical diagnosis of a genetically heterogeneous recessive disease, especially in small-sized families.

• ISBN or ISSN: 1471-2350

• 본 연구는 질병관리본부 연구개발과제(과제번호 2012-N61001-00) 연구비를 지원받아 수행되었습니다.
• This research was supported by a fund(code 2012-N61001-00) by Research of Korea Centers for Disease Control and Prevention.