Research

Orphanet Journal of Rare Diseases

, 7:60

Open Access This content is freely available online to anyone, anywhere at any time.

Targeted massive parallel sequencing: the effective detection of novel causative mutations associated with hearing loss in small families

  • Jeong-In BaekAffiliated withDepartment of Biology, College of Natural Sciences, Kyungpook National University
  • , Se-Kyung OhAffiliated withDepartment of Biology, College of Natural Sciences, Kyungpook National University
  • , Dong-Bin KimAffiliated withDepartment of Biology, College of Natural Sciences, Kyungpook National University
  • , Soo-Young ChoiAffiliated withDepartment of Biology, College of Natural Sciences, Kyungpook National University
  • , Un-Kyung KimAffiliated withDepartment of Biology, College of Natural Sciences, Kyungpook National University Email author 
  • , Kyu-Yup LeeAffiliated withDepartment of Otolaryngology, College of Medicine, Kyungpook National University Email author 
  • , Sang-Heun LeeAffiliated withDepartment of Otolaryngology, College of Medicine, Kyungpook National University

Abstract

Background

Hereditary hearing loss is one of the most common heterogeneous disorders, and genetic variants that can cause hearing loss have been identified in over sixty genes. Most of these hearing loss genes have been detected using classical genetic methods, typically starting with linkage analysis in large families with hereditary hearing loss. However, these classical strategies are not well suited for mutation analysis in smaller families who have insufficient genetic information.

Methods

Eighty known hearing loss genes were selected and simultaneously sequenced by targeted next-generation sequencing (NGS) in 8 Korean families with autosomal dominant non-syndromic sensorineural hearing loss.

Results

Five mutations in known hearing loss genes, including 1 nonsense and 4 missense mutations, were identified in 5 different genes (ACTG1, MYO1F, DIAPH1, POU4F3 and EYA4), and the genotypes for these mutations were consistent with the autosomal dominant inheritance pattern of hearing loss in each family. No mutational hot-spots were revealed in these Korean families.

Conclusion

Targeted NGS allowed for the detection of pathogenic mutations in affected individuals who were not candidates for classical genetic studies. This report is the first documenting the effective use of an NGS technique to detect pathogenic mutations that underlie hearing loss in an East Asian population. Using this NGS technique to establish a database of common mutations in Korean patients with hearing loss and further data accumulation will contribute to the early diagnosis and fundamental therapies for hereditary hearing loss.

Keywords

Hearing loss Heterogeneous Next-generation sequencing Mutation Gene