title: A rapid method for simultaneous screening of multi-gene mutations associated with hearing loss in the Korean population.
abstract: Hearing loss (HL) is a congenital disease with a high prevalence, and patients with hearing loss need early diagnosis for treatment and prevention. The GJB2, MT-RNR1, and SLC26A4 genes have been reported as common causative genes of hearing loss in the Korean population and some mutations of these genes are the most common mutations associated with hearing loss. Accordingly, we developed a method for the simultaneous detection of seven mutations (c.235delC of GJB2, c.439A>G, c.919-2A>G, c.1149+3A>G, c.1229C>T, c.2168A>G of SLC26A4, and m.1555A>G of the MT-RNR1 gene) using multiplex SNaPshot minisequencing to enable rapid diagnosis of hereditary hearing loss. This method was confirmed in patients with hearing loss and used for genetic diagnosis of controls with normal hearing and neonates. We found that 4.06% of individuals with normal hearing and 4.32% of neonates were heterozygous carriers. In addition, we detected that an individual is heterozygous for two different mutations of GJB2 and SLC26A4 gene, respectively and one normal hearing showing the heteroplasmy of m.1555A>G. These genotypes corresponded to those determined by direct sequencing. Overall, we successfully developed a robust and cost-effective diagnosis method that detects common causative mutations of hearing loss in the Korean population. This method will be possible to detect up to 40% causative mutations associated with prelingual HL in the Korean population and serve as a useful genetic technique for diagnosis of hearing loss for patients, carriers, neonates, and fetuses.
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.forename: Jeong-In
authors.initials: JI
authors.lastname: Baek
authors.forename: Se-Kyung
authors.initials: SK
authors.lastname: Oh
authors.forename: Kyung Jin
authors.initials: KJ
authors.lastname: Na
authors.forename: Jae Woong
authors.initials: JW
authors.lastname: Bae
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Choi
authors.forename: Ji Yun
authors.initials: JY
authors.lastname: Jeong
authors.forename: Jae Young
authors.initials: JY
authors.lastname: Choi
authors.forename: Sang-Heun
authors.initials: SH
authors.lastname: Lee
authors.forename: Kyu-Yup
authors.initials: KY
authors.lastname: Lee
authors.forename: Un-Kyung
authors.initials: UK
authors.lastname: Kim
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D003638:Deafness / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005820:Genetic Testing / Q000379:methods; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction; D009154:Mutation; D012335:RNA, Ribosomal / Q000235:genetics*; D056910:Republic of Korea / Q000453:epidemiology; D017422:Sequence Analysis, DNA / Q000379:methods; D000076988:Sulfate Transporters
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D026901:Membrane Transport Proteins; D012335:RNA, Ribosomal; C075526:RNA, ribosomal, 12S; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters; D000072259:Connexin 26