title: Mutation Spectrum of Common Deafness-Causing Genes in Patients with Non-Syndromic Deafness in the Xiamen Area, China.
abstract: In China, approximately 30,000 babies are born with hearing impairment each year. However, the molecular factors causing congenital hearing impairment in the Xiamen area of Fujian province have not been evaluated. To provide accurate genetic testing and counseling in the Xiamen area, we investigated the molecular etiology of non-syndromic deafness in a deaf population from Xiamen. Unrelated students with hearing impairment (n = 155) who attended Xiamen Special Education School in Fujian Province were recruited for this study. Three common deafness-related genes, GJB2, SLC26A4, and mtDNA12SrRNA, were analyzed using all-exon sequencing. GJB2 mutations were detected in 27.1% (42/155) of the entire cohort. The non-syndromic hearing loss (NSHL) hotspot mutations c.109G>A (p.V37I) and c.235delC were found in this population, whereas the Caucasian hotspot mutation c.35delG was not. The allelic frequency of the c.109G>A mutation was 9.03% (28/310), slightly higher than that of c.235delC (8.39%, 26/310), which is the most common GJB2 mutation in most areas of China. The allelic frequency of the c.109G>A mutation was significantly higher in this Xiamen's deaf population than that in previously reported cohorts (P = 0.00). The SLC26A4 mutations were found in 16.77% (26/155) of this cohort. The most common pathogenic allele was c.IVS7-2A>G (6.13%, 19/310), and the second most common was the c.1079C>T (p.A360V) mutation (1.94%, 6/310) which has rarely been reported as a hotspot mutation in other studies. The mutation rate of mtDNA12SrRNA in this group was 3.87% (6/155), all being the m.A1555G mutation. These findings show the specificity of the common deaf gene-mutation spectrum in this area. According to this study, there were specific hotspot mutations in Xiamen deaf patients. Comprehensive sequencing analysis of the three common deaf genes can help portray the mutation spectrum and develop optimal testing strategies for deaf patients in this area.
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, PLA General Hospital, Beijing, P. R. China; Fujian Medical University ShengLi clinical college, Fujian Provincial Hospital, Fuzhou, P. R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, PLA General Hospital, Beijing, P. R. China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Huang
authors.affiliation: Beijing Capital Bio Independent Clinical Laboratory, Beijing, P. R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Deng
authors.affiliation: Fujian Medical University ShengLi clinical college, Fujian Provincial Hospital, Fuzhou, P. R. China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Wu
authors.affiliation: Fujian Medical University ShengLi clinical college, Fujian Provincial Hospital, Fuzhou, P. R. China.
authors.forename: Juan
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, PLA General Hospital, Beijing, P. R. China.
authors.forename: Dongyang
authors.initials: D
authors.lastname: Kang
authors.affiliation: Beijing Capital Bio Independent Clinical Laboratory, Beijing, P. R. China.
authors.forename: Xiufeng
authors.initials: X
authors.lastname: Xu
authors.affiliation: Fujian Medical University ShengLi clinical college, Fujian Provincial Hospital, Fuzhou, P. R. China.
authors.forename: Ruiyu
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, PLA General Hospital, Beijing, P. R. China.
authors.forename: Dongyi
authors.initials: D
authors.lastname: Han
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, PLA General Hospital, Beijing, P. R. China.
authors.forename: Pu
authors.initials: P
authors.lastname: Dai
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D000595:Amino Acid Sequence; D002648:Child; D002675:Child, Preschool; D002681:China; D015331:Cohort Studies; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D004252:DNA Mutational Analysis; D003638:Deafness / Q000235:genetics; D005091:Exons; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D012313:RNA / Q000235:genetics*; D000077278:RNA, Mitochondrial; D012335:RNA, Ribosomal / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D000076988:Sulfate Transporters; D055815:Young Adult
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D026901:Membrane Transport Proteins; D000077278:RNA, Mitochondrial; D012335:RNA, Ribosomal; C075526:RNA, ribosomal, 12S; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters; D000072259:Connexin 26; D012313:RNA