[Mitochondrial DNA G7444A mutation may influence the phenotypic manifestation of the deafness-associated 12S rRNA A1555G mutation].
Mitochondrial 12S rRNA and tRNASer(UCN) genes are the hot spots for mutations associated with hearing loss. We reported here the clinical, genetic and molecular analysis of a Chinese pedigree with maternally inherited sensorineural hearing loss. Molecular analysis showed that the pedigree carried both mitochondrial DNA (mtDNA) A1555G and G7444A mutations. The penetrance of hearing loss in this pedigree was 58% when aminoglycoside-induced hearing loss was included. When the effect of aminoglycosides was excluded, the penetrance of hearing loss in this pedigree was 25%. The penetrance of hearing loss was significantly higher than other families carrying only A1555G mutation. Sequence analysis of the complete mitochondrial genome in the proband showed that there were 28 mtDNA polymorphisms belonging to East-Asian haplogroup B4c1. In addition to the deafness-associated A1555G and G7444A mutations, there were no other functionally significant variants found in this family. This indicated that mtDNA G7444A mutation may aggravate mitochondrial dysfunction associated with the A1555G mutation. Therefore, the coexistence of both mtDNA mutations may contribute to high penetrance of hearing loss.
Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou 325035, China. aifenyang.wzmc@gmail.com
Ai-Fen
AF
Yang
Yi
Y
Zhu
Jian-Xin
JX
Lu
Li
L
Yang
Jian-Yue
JY
Zhao
Dong-Mei
DM
Sun
D000617:Aminoglycosides / Q000009:adverse effects; D002648:Child; D004272:DNA, Mitochondrial / Q000235:genetics*; D003638:Deafness / Q000235:genetics*; D005260:Female; D034381:Hearing Loss / Q000139:chemically induced / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics; D012335:RNA, Ribosomal / Q000235:genetics*
D000617:Aminoglycosides; D004272:DNA, Mitochondrial; D012335:RNA, Ribosomal; C075526:RNA, ribosomal, 12S