Novel mitochondrial gene variants in Northwestern Chinese probands with non-syndromic hearing loss by whole mitochondrial genome screening

Xiaowan Chen; Fang Wang; Aishanjiang Maerhaba; Qianqian Li; Jianchao Wang; Xiaowen Liu; Jing Zheng; Ye Chen; YuFen Guo

doi:10.1016/j.gene.2018.01.098

Novel mitochondrial gene variants in Northwestern Chinese probands with non-syndromic hearing loss by whole mitochondrial genome screening

Gene. 2018 Apr 30:652:59-65. doi: 10.1016/j.gene.2018.01.098. Epub 2018 Jan 31.

Authors

Xiaowan Chen¹, Fang Wang², Aishanjiang Maerhaba³, Qianqian Li³, Jianchao Wang², Xiaowen Liu², Jing Zheng⁴, Ye Chen³, YuFen Guo⁵

Affiliations

¹ Department of Otolaryngology-Head and Neck Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu Province 730000, China; Department of Otolaryngology-Head and Neck Surgery, Lanzhou University First Hospital, Lanzhou, Gansu Province 730000, China.
² Department of Otolaryngology-Head and Neck Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu Province 730000, China.
³ Institute of Genetics, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310058, China.
⁴ Division of Medical Genetics and Genomics, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310058, China; Department of Genetic and Metabolic Diseases, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310058, China.
⁵ Department of Otolaryngology-Head and Neck Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu Province 730000, China; Health and Family Planning Commission of Gansu Province, Lanzhou, Gansu Province 730000, China. Electronic address: guoyflz@163.com.

PMID: 29408584
DOI: 10.1016/j.gene.2018.01.098

Abstract

Mitochondrial DNA mutations play an important role in hereditary hearing loss. The present study aimed at identifying more novel genetic variants of mitochondrial DNA. Complete Mitochondrial genomes were detected in 97 Northwestern Chinese probands with non-syndromic hearing loss and 376 control subjects. The variants were evaluated for the pathogenicity using the following criteria: (1) present in <1% of the controls, (2) evolutional conservation, (3) potential structural and functional alterations. Mutational analysis in probands identified 706 variants, including 180 variants in the D loop region, 27 variants in the 12S rRNA gene, 29 variants in the 16S rRNA gene, 122 missense variants and 312 silent variants in the protein coding gene, 29 variants in the tRNA genes and 7 variants in the non-coding region. After further analysis assessed for the potential structural and functional significance, we identified 5 new candidate variants for hearing loss: 12S rRNA1473C>T, tRNA^Phe 614A>C, tRNA^Lys 8339A>G, ND1 3866T>C and non-coding 5656A>G. Our findings may provide the role of these genes in hearing loss development in China and valuable information for the further understanding of pathogenic mechanism of hearing loss.

Keywords: Mitochondrial DNA; Mitochondrial dysfunction; Non-syndromic hearing loss; Novel mutations.

MeSH terms

Adolescent
Adult
Asian People
Case-Control Studies
Child
Child, Preschool
DNA, Mitochondrial / genetics*
Female
Genes, Mitochondrial*
Genome, Mitochondrial*
Hearing Loss, Bilateral / diagnosis
Hearing Loss, Bilateral / ethnology
Hearing Loss, Bilateral / genetics*
Hearing Loss, Bilateral / physiopathology
High-Throughput Nucleotide Sequencing
Humans
Male
Middle Aged
Mutation
Pedigree
RNA, Ribosomal / genetics*
RNA, Ribosomal, 16S / genetics
RNA, Transfer / genetics

Substances

DNA, Mitochondrial
RNA, Ribosomal
RNA, Ribosomal, 16S
RNA, ribosomal, 12S
RNA, Transfer