title: Maternally inherited non-syndromic hearing loss associated with mitochondrial 12S rRNA A827G mutation in a Chinese family.
abstract: We explored the clinical and molecular characterization of a Chinese family with non-syndromic hearing impairment. Clinical evaluations revealed a possible maternal inheritance pattern, and showed an extremely similar phenotype of hearing loss including the age of onset, severity, and audiometric configuration. Sequence analysis of the mitochondrial 12S rRNA and tRNA(Ser(UCN)) genes led to the identification of a homoplasmic A827G mutation in all maternal relatives, which was absent in other family members and 40 Chinese controls. This mutation has previously been reported sporadically in a few individuals with aminoglycoside-induced and non-syndromic hearing loss. The A827G mutation is located at the A-site of the mitochondrial 12S rRNA gene which is highly evolutionarily conserved in mammals. The occurrence of the A827G mutation in these genetically unrelated subjects strongly suggests that this mutation is involved in the pathogenesis of hearing impairment. However, incomplete penetrance of hearing loss indicates that the A827G mutation alone is not sufficient to produce clinical phenotype but requires the involvement of modifier factors for the phenotypic expression, even though aminoglycosides and GJB2 gene may not contribute to the penetrance of the A827G mutation in this Chinese family. In contrast with the variable phenotype of hearing loss associated with other mitochondrial mutations, all of the patients in our family exhibited strikingly similar clinical features. This discrepancy likely reflects the difference of genetic backgrounds between this pedigree and others.
authors.affiliation: Department of Otolaryngology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. xing-gq@163.com
authors.forename: Guangqian
authors.initials: G
authors.lastname: Xing
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Chen
authors.forename: Qinjun
authors.initials: Q
authors.lastname: Wei
authors.forename: Huiqin
authors.initials: H
authors.lastname: Tian
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Li
authors.forename: Aidong
authors.initials: A
authors.lastname: Zhou
authors.forename: Xingkuan
authors.initials: X
authors.lastname: Bu
authors.forename: Xin
authors.initials: X
authors.lastname: Cao
mesh_terms: D044466:Asian People / Q000235:genetics*; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D050259:Genes, Mitochondrial / Q000235:genetics*; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D019683:Penetrance; D012335:RNA, Ribosomal
chemical_list: D017630:Connexins; D004272:DNA, Mitochondrial; C000607042:GJB2 protein, human; D012335:RNA, Ribosomal; C075526:RNA, ribosomal, 12S; D000072259:Connexin 26