title: SNaPshot reveals high mutation and carrier frequencies of 15 common hearing loss mutants in a Chinese newborn cohort.
abstract: Genetic causes account for more than half of congenital hearing loss cases. The most frequent mutations found in non-syndromic hearing loss patients occur in GJB2 and SLC26A4. Mitochondrial genome mutations are also prevalent. However, the frequency of common hearing loss mutations in the Chinese population has not yet been well estimated. Here, we implemented the SNaPshot genotyping method to investigate the carrier frequency of 15 commonly reported hearing loss mutations in GJB2, SLC26A4 and the mitochondrial genome based on a cohort of 5800 neonates in China. Up to 15.9% (923/5800) of the newborns carry at least one mutant allele. The top three were GJB2-c.109G>A, GJB2-c.235delC, and SLC26A4-c.919A>G, with notably high carrier frequencies of 1/10, 1/53 and 1/62 respectively, and mt-7444G>A with 1/141 was the most frequent allele in the mitochondrial genome. In this cohort, 0.48% (28/5800) of neonates were genetically diagnosed with hearing loss, from which seven cases failed an OAE test. This is the first epidemiological study of non-syndromic hearing loss in Chinese newborns indicating a notably high carrier frequency (1 per 6.3 newborns) among these 15 mutant alleles. Our carrier frequency data also aid in effective risk assessment and genetic counseling for hearing loss patients in the Chinese population.
authors.affiliation: Department of Neotology, Central Lab Suzhou Hospital Affiliated to Nanjing Medical University, Suzhou, Jiangsu, 215002, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: Y
authors.initials: Y
authors.lastname: Cao
authors.forename: H-B
authors.initials: HB
authors.lastname: Li
authors.forename: J
authors.initials: J
authors.lastname: Mao
authors.forename: M-J
authors.initials: MJ
authors.lastname: Liu
authors.forename: Y-H
authors.initials: YH
authors.lastname: Liu
authors.forename: B-J
authors.initials: BJ
authors.lastname: Wang
authors.forename: D
authors.initials: D
authors.lastname: Jiang
authors.forename: Q
authors.initials: Q
authors.lastname: Zhu
authors.forename: Y
authors.initials: Y
authors.lastname: Ding
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.forename: K W
authors.initials: KW
authors.lastname: Choy
mesh_terms: D000483:Alleles; D044466:Asian People / Q000235:genetics*; D002681:China / Q000453:epidemiology; D015331:Cohort Studies; D000072259:Connexin 26; D017630:Connexins; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing / Q000379:methods; D034381:Hearing Loss / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009154:Mutation
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26
keywords: carrier frequency; genetic diagnosis; hearing loss; newborn screening