Mitochondrial 12S rRNA A1555G mutation associated with nonsyn-dromic hearing loss in twenty-five Han Chinese pedigrees

Abstract Background Hearing loss is among the most frequent sensory disorders. Preventable causes include medications given to genetically susceptible individuals. Several families around the world with an A1555G mitochondrial mutation who became profoundly deaf after receiving aminoglycosides have been described. However, none has been reported in Thailand. Objectives To identify the cause of hearing loss of a large Thai family with 11 members who reportedly turned deaf after receiving antibiotics. Methods We obtained blood samples from 5 members; 4 of whom had hearing loss. Mutation analyses were performed using molecular techniques including polymerase chain reaction, Sanger sequencing, and restriction fragment length polymorphism. Results All 4 affected members were found to harbor the same A1555G mitochondrial mutation, while the unaffected had only the wild-type A. Conclusions We have identified the mitochondrial mutation leading to aminoglycoside-induced hearing loss in a Thai population. Raising awareness for medical practitioners of this genetic susceptibility in Thailand is warranted. Avoidance of certain medications in these individuals would prevent this acquired permanent hearing loss.

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Associations between GJB2, Mitochondrial 12S rRNA, SLC26A4 Mutations, and Hearing Loss among Three Ethnicities

BioMed Research International ◽

10.1155/2014/746838 ◽

2014 ◽

Vol 2014 ◽

pp. 1-6 ◽

Cited By ~ 8

Author(s):

Wan Du ◽

Qiuju Wang ◽

Yiming Zhu ◽

Yanli Wang ◽

Yufen Guo

Keyword(s):

Hearing Loss ◽

Sensorineural Hearing Loss ◽

Direct Sequencing ◽

Han Chinese ◽

Chinese Patients ◽

12S Rrna ◽

Mutational Spectrum ◽

Mitochondrial 12S Rrna ◽

Homozygous Mutations ◽

Gjb2 Mutations

The epidemiological researches show that the mutations of GJB2, mitochondrial 12S rRNA, and SLC26A4 genes have played an important role in the hearing loss. This study aims to investigate the mutation spectrum of GJB2, mitochondrial 12S rRNA, and SLC26A4 genes of Han Chinese, Hui people, and Uyghur ethnicities in sensorineural hearing loss (SNHL) patients in northwest of China. Mutational analyses in the three genes were brought by direct sequencing and each fragment was analyzed using an ABI 3730 DNA Sequencer. The mutation frequencies for the three HL causative genes were 34.05% in Han Chinese participants, 27.47% in Hui people, and 14.44% in Uyghur participants, respectively. The prevalence of GJB2 mutations was 13.7%, 11.4%, and 11.4% in Han Chinese, Hui people, and Uyghur participants (χ2=10.2,P<0.05), respectively. The prevalence of mtDNA 12S rRNA A1555G homozygous mutations was 6.05%, 3.27%, and 1.44% in Han Chinese, Hui people, and Uyghur participants (χ2=13.9,P<0.05), respectively. The prevalence of SLC26A4 mutations was 14.3%, 12.8%, and 1.6% in Han Chinese, Hui people, and Uyghur participants, respectively. In summary, we find that Uyghur and Hui SNHL individuals vary significantly from Han Chinese patients in three causative HL genes' mutational spectrum, especially for Uyghur.

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Co-segregation of the T1095C with the A1555G mutation of the mitochondrial 12S rRNA gene in a patient with non-syndromic hearing loss

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2008.10.132 ◽

2008 ◽

Vol 377 (4) ◽

pp. 1152-1155 ◽

Cited By ~ 4

Author(s):

Dachun Dai ◽

Yajie Lu ◽

Zhibin Chen ◽

Qinjun Wei ◽

Xin Cao ◽

...

Keyword(s):

Hearing Loss ◽

12S Rrna ◽

Rrna Gene ◽

A1555g Mutation ◽

12S Rrna Gene ◽

Mitochondrial 12S Rrna ◽

Syndromic Hearing Loss

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Very low penetrance of hearing loss in seven Han Chinese pedigrees carrying the deafness-associated 12S rRNA A1555G mutation

Gene ◽

10.1016/j.gene.2007.01.001 ◽

2007 ◽

Vol 393 (1-2) ◽

pp. 11-19 ◽

Cited By ~ 39

Author(s):

Xiaowen Tang ◽

Li Yang ◽

Yi Zhu ◽

Zhisu Liao ◽

Jindan Wang ◽

...

Keyword(s):

Hearing Loss ◽

Han Chinese ◽

12S Rrna ◽

A1555g Mutation

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Analysis of the heteroplasmy level and transmitted features in hearing-loss pedigrees with mitochondrial 12S rRNA A1555G mutation

BMC Genetics ◽

10.1186/1471-2156-15-26 ◽

2014 ◽

Vol 15 (1) ◽

pp. 26 ◽

Cited By ~ 8

Author(s):

Yuhua Zhu ◽

Shasha Huang ◽

Dongyang Kang ◽

Mingyu Han ◽

Guojian Wang ◽

...

Keyword(s):

Hearing Loss ◽

12S Rrna ◽

A1555g Mutation ◽

Mitochondrial 12S Rrna

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Interaction of Aminoglycosides with Human Mitochondrial 12S rRNA Carrying the Deafness-Associated Mutation

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00965-08 ◽

2009 ◽

Vol 53 (11) ◽

pp. 4612-4618 ◽

Cited By ~ 56

Author(s):

Yaping Qian ◽

Min-Xin Guan

Keyword(s):

Hearing Loss ◽

Chemical Modification ◽

Conformational Changes ◽

Dimethyl Sulfate ◽

12S Rrna ◽

A1555g Mutation ◽

Mitochondrial 12S Rrna ◽

A Site ◽

Insight Into ◽

Type Sequence

ABSTRACT The mitochondrial 12S rRNA A1555G mutation is one of the important causes of aminoglycoside-induced and nonsyndromic hearing loss. Here we employed an RNA-directed chemical-modification approach to understanding the pathogenesis of aminoglycoside-induced hearing loss. The patterns of chemical modification of RNA oligonucleotides carrying the A1555G mutation by dimethyl sulfate (DMS) were distinct from those of the RNA oligonucleotides carrying wild-type sequence in the presence of aminoglycosides. In the RNA analogue carrying the A1555G mutation, reduced reactivity to DMS occurred in base G1555 as well as in bases C1556 and A1553 in the presence of paromomycin, neomycin, gentamicin, kanamycin, tobramycin, or streptomycin. In particular, base G1555 exhibited marked but similar levels of protection in the presence of 0.1 μM to 100 μM neomycin, gentamicin, or kanamycin. In contrast, the levels of protection in base G1555 appeared to be correlated with the concentration of paromycin, tobramycin, or steptomycin. Furthermore, increasing reactivities to DMS in the presence of these aminoglycosides were observed for bases A1492, C1493, C1494, and A1557 in the RNA analogue carrying the A1555G mutation. These data suggested that the A1555G mutation altered the binding properties of aminoglycosides at the A site of 12S rRNA and led to local conformational changes in 12S rRNA carrying the A1555G mutation. The interaction between aminoglycosides and 12S rRNA carrying the A1555G mutation provides new insight into the pathogenesis of aminoglycoside ototoxicity.

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