title: Evaluation of the contribution of the EYA4 and GRHL2 genes in Korean patients with autosomal dominant non-syndromic hearing loss.
abstract: EYA4 and GRHL2 encode transcription factors that play an important role in regulating many developmental stages. Since EYA4 and GRHL2 were identified as the transcription factors for the DFNA10 and DFNA28, 8 EYA4 mutations and 2 GRHL2 mutations have been reported worldwide. However, these genes have been reported in few studies of the Korean population. In this study, we performed a genetic analysis of EYA4 and GRHL2 in 87 unrelated Korean patients with autosomal dominant non-syndromic hearing loss (NSHL). A total of 4 genetic variants in the EYA4 gene were identified, including the 2 nonsense mutations p.S288X and p.Q393X. The novel mutation p.Q393X (c.1177C>T) resulted in a change in the codon at amino acid position 393 from a glutamine to a stop codon. The p.Q393X allele was predicted to encode a truncated protein lacking the entire C-terminal Eya homolog region (Eya HR), which is essential for the interaction with the transcription factor SIX3. The p.S288X (c.863C>A) mutation was found in a Korean family from a previous study. We analyzed p.S288X-linked microsatellite markers and determined that p.S288X might be a founder mutation and a hotspot mutation in Koreans. In GRHL2, a total of 4 genetic variants were identified, but none were associated with hearing loss in Korean patients. This suggests that GRHL2 may not be a main causal gene for autosomal dominant NSHL in Korean patients. In conclusion, our data provide fundamental information to predict the genotypes of Korean patients diagnosed with autosomal dominant NSHL.
authors.affiliation: Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu, Republic of Korea; School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Ye-Ri
authors.initials: YR
authors.lastname: Kim
authors.affiliation: Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu, Republic of Korea; School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Min-A
authors.initials: MA
authors.lastname: Kim
authors.affiliation: Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu, Republic of Korea; School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Borum
authors.initials: B
authors.lastname: Sagong
authors.affiliation: Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu, Republic of Korea; School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Seung-Hyun
authors.initials: SH
authors.lastname: Bae
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Hallym University College of Medicine, Anyang, Republic of Korea.
authors.forename: Hyo-Jeong
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Hallym University College of Medicine, Anyang, Republic of Korea.
authors.forename: Hyung-Jong
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jae Young
authors.initials: JY
authors.lastname: Choi
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Kyu-Yup
authors.initials: KY
authors.lastname: Lee
authors.affiliation: Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu, Republic of Korea; School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Un-Kyung
authors.initials: UK
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D005838:Genotype; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D020080:Tandem Repeat Sequences / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; C117736:EYA4 protein, human; C470830:GRHL2 protein, human; D015534:Trans-Activators; D014157:Transcription Factors