title: The ND4 G11696A mutation may influence the phenotypic manifestation of the deafness-associated 12S rRNA A1555G mutation in a four-generation Chinese family.
abstract: We report here the clinical, genetic and molecular characterization of a large Han Chinese family with aminoglycoside-induced and nonsyndromic hearing loss. The penetrance of hearing loss (affected matrilineal relatives/total matrilineal relatives) in this pedigree was 53%, when aminoglycoside-induced deafness was included. When the effect of aminoglycosides was excluded, the penetrance of hearing loss in this pedigree was 42%. These matrilineal relatives exhibited a wide range of severity of hearing loss, varying from profound to normal hearing. Furthermore, these affected matrilineal relatives shared some common features: bilateral hearing loss of high frequencies and symmetries. Sequence analysis of mitochondrial DNA (mtDNA) in the pedigree identified the homoplasmic 12S rRNA A1555G mutation and other 35 variants belonging to Eastern Asian haplogroup D4. Of these, the V313I (G11696A) mutation in ND4 was associated with vision loss. However, the extremely low penetrance of visual loss, and the mild biochemical defect and the presence of one/167 Chinese controls indicted that the G11696A mutation is itself not sufficient to produce a clinical phenotype. Thus, the G11696A mutation may act in synergy with the primary deafness-associated 12S rRNA A1555G mutation in this Chinese family, thereby increasing the penetrance and expressivity of hearing loss in this Chinese pedigree.
authors.affiliation: Department of Otolaryngology, The First Affiliated Hospital, Wenzhou Medical College, Wenzhou, Zhejiang, China.
authors.forename: Zhisu
authors.initials: Z
authors.lastname: Liao
authors.forename: Jianyue
authors.initials: J
authors.lastname: Zhao
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhu
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Aifen
authors.initials: A
authors.lastname: Yang
authors.forename: Dongmei
authors.initials: D
authors.lastname: Sun
authors.forename: Zhongnong
authors.initials: Z
authors.lastname: Zhao
authors.forename: Xinjian
authors.initials: X
authors.lastname: Wang
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Tao
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Tang
authors.forename: Jindan
authors.initials: J
authors.lastname: Wang
authors.forename: Minqiang
authors.initials: M
authors.lastname: Guan
authors.forename: Jiafu
authors.initials: J
authors.lastname: Chen
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Li
authors.forename: Jianxin
authors.initials: J
authors.lastname: Lu
authors.forename: Min-Xin
authors.initials: MX
authors.lastname: Guan
mesh_terms: D000293:Adolescent; D002681:China; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics; D004272:DNA, Mitochondrial / Q000378:metabolism; D003638:Deafness / Q000235:genetics*; D005260:Female; D034381:Hearing Loss / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D009245:NADH Dehydrogenase / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D012335:RNA, Ribosomal / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D017630:Connexins; D004272:DNA, Mitochondrial; C098483:NADH dehydrogenase subunit 4; D012335:RNA, Ribosomal; C075526:RNA, ribosomal, 12S; D000072259:Connexin 26; D009245:NADH Dehydrogenase