title: Identification of a nonsense mutation in the STRC gene in a Korean family with moderate hearing loss.
abstract: Hereditary hearing loss is a heterogeneous disorder that results in a common sensorineural disorder. To date, more than 150 loci and 89 genes have been reported for non-syndromic hearing loss. Next generation sequencing has recently been developed as a powerful genetic strategy for identifying pathogenic mutations in heterogeneous disorders with various causative genes. In this study, we performed targeted sequencing to identify the causative mutation in a Korean family that had moderate hearing loss. We targeted 64 genes associated with non-syndromic hearing loss and sorted the homozygous variations according to the autosomal recessive inheritance pattern of the family. Implementing a bioinformatic platform for filtering and detecting variations allowed for the identification of two variations within different genes (c.650G>A in TRIOBP and c.4057C>T in STRC). These variants were selected for further analysis. Among these, c.4057C>T (p.Q1353X) was a divergent sequence variation between the STRC gene and the STRC pseudogene. This was the critical difference that resulted in loss of the protein-coding ability of the pseudogene. Therefore, we hypothesized that the p.Q1353X variation in the STRC gene is the causative mutation for hearing loss. This result suggests that application of targeted sequencing will be valuable for the diagnosis of heterogeneous disorders.
authors.affiliation: Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu, South Korea.
authors.forename: Borum
authors.initials: B
authors.lastname: Sagong
authors.affiliation: Division of Nephrology, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Jeong-In
authors.initials: JI
authors.lastname: Baek
authors.affiliation: Department of Anatomy, BrainKorea21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Jinwoong
authors.initials: J
authors.lastname: Bok
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, School of Medicine, Kyungpook National University, Daegu, South Korea. Electronic address: kylee@knu.ac.kr.
authors.forename: Kyu-Yup
authors.initials: KY
authors.lastname: Lee
authors.affiliation: Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu, South Korea; School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, South Korea. Electronic address: kimuk@knu.ac.kr.
authors.forename: Un-Kyung
authors.initials: UK
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D044466:Asian People / Q000235:genetics*; D018389:Codon, Nonsense; D019295:Computational Biology; D004252:DNA Mutational Analysis; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006720:Homozygote; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D010375:Pedigree; D011544:Pseudogenes / Q000235:genetics*; D056910:Republic of Korea
chemical_list: D018389:Codon, Nonsense; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C499079:STRC protein, human
keywords: DFNB16; Hearing loss; STRC; Stereocilin; Targeted sequencing