Genetic association of MYH genes with hereditary hearing loss in Korea

• Published in: Gene 2016-10, Vol.591 (1), p.177-182
• Main Authors: Kim, Sang-Joo, Lee, Seokwon, Park, Hong-Joon, Kang, Tae-Hun, Sagong, Borum, Baek, Jeong-In, Oh, Se-Kyung, Choi, Jae Young, Lee, Kyu-Yup, Kim, Un-Kyung
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Base Sequence; DNA Mutational Analysis; Female; Genetic Association Studies; Genetic Predisposition to Disease; Hearing Loss, Sensorineural - genetics; Humans; Male; Mutation, Missense - genetics; MYH14 gene; MYH9 gene; Myosin; Myosin Heavy Chains - chemistry; Myosin Heavy Chains - genetics; Non-muscle myosin heavy chain; Non-syndromic hearing loss; Pedigree; Republic of Korea
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2016.07.011

Myosin is a key protein involved in regulating the shape and motility of cells. The MYH9 and MYH14 genes, which encode non-muscle myosin heavy chain IIA (NMMHC II-A) and IIC (NMMHC II-C), respectively, are expressed in the inner ear. These myosin genes are known to be associated with autosomal dominant non-syndromic hearing loss (ADNSHL); however, genetic studies in patients with ADNSHL in Korea have rarely been reported. We analyzed the MYH9 and MYH14 genes in 75 Korean patients with ADNSHL. We identified 4 possible pathogenic variants: a novel variant p.F1303L and 2 previously reported variants (p.R1730C and p.R1785C) in the MYH9 gene, and a novel variant p.A1868T in the MYH14 gene. All the variants were located in the myosin tail domain, which is essential for the interaction of myosin with actin. These variants were predicted to be possibly pathogenic by functional prediction tools and were absent in 100 unrelated normal controls. These results suggest that all the variants identified in this study have a strong potential to affect the structural stability and/or function of non-muscle myosin in the inner ear, which might lead to ADNSHL. This study establishes the link between the genotype and development of ADNSHL and contributes to the establishment of Korean database for hereditary hearing loss. •We performed genetic analysis of MYH genes in Korean patients with ADNSHL.•We found three and one possibly pathogenic variants in MYH9 and MYH14, respectively.•Our research will improve understanding of relations between MYH genes and ADNSHL.