Distribution of mitochondrial MT-RNR1, MT-TL1, MT-TS1, MT-TK and MT-TE genes variants associated with hearing loss in Southwestern China

Shiyu Zhou; Menglan Chen; Jiahong Pei; Chen Zhang; Xiaofei Ren; Jingyu Li; Yaliang Sa; Baosheng Zhu; Yunlong Li

doi:10.1016/j.ijporl.2024.111979

Distribution of mitochondrial MT-RNR1, MT-TL1, MT-TS1, MT-TK and MT-TE genes variants associated with hearing loss in Southwestern China

Int J Pediatr Otorhinolaryngol. 2024 May 9:181:111979. doi: 10.1016/j.ijporl.2024.111979. Online ahead of print.

Authors

Shiyu Zhou¹, Menglan Chen¹, Jiahong Pei², Chen Zhang¹, Xiaofei Ren¹, Jingyu Li¹, Yaliang Sa³, Baosheng Zhu⁴, Yunlong Li⁵

Affiliations

¹ Department of Medical Genetics, The First People's Hospital of Yunnan Province, Kunming, Yunnan, China; The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China.
² The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China.
³ The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China. Electronic address: sayalian@126.com.
⁴ Department of Medical Genetics, The First People's Hospital of Yunnan Province, Kunming, Yunnan, China; The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China; National Health Commission Key Laboratory of Healthy Birth and Birth Defect Prevention in Western China, Kunming, Yunnan, China. Electronic address: bszhu@aliyun.com.
⁵ Department of Medical Genetics, The First People's Hospital of Yunnan Province, Kunming, Yunnan, China; The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China; National Health Commission Key Laboratory of Healthy Birth and Birth Defect Prevention in Western China, Kunming, Yunnan, China. Electronic address: yunlongli.km@qq.com.

PMID: 38739980
DOI: 10.1016/j.ijporl.2024.111979

Abstract

Background: Maternally inherited hearing loss has been associated with mitochondrial genes, including MT-RNR1, MT-TL1, MT-TS1, MT-TK and MT-TE. Among these genes, MT-RNR1 is known to be a hotspot for pathogenic variants related to aminoglycoside ototoxicity and nonsyndromic hearing loss. However, the frequency and spectrum of variants in these genes, particularly in multi-ethnic hearing loss patients from Southwestern China, are still not fully understood.

Methods: In this study, we enrolled 460 hearing loss patients from various ethnic backgrounds (Han, Yi, Dai, Hani, etc.) in Southwestern China. Next-generation sequencing was used to analyze the mitochondrial MT-RNR1, MT-TL1, MT-TS1, MT-TK and MT-TE genes. Subsequently, bioinformatical methods were employed to evaluate the identified variants.

Results: Among the patients with hearing loss, we identified 70 variants in MT-RNR1 (78.6 %, 55/70), MT-TL1 (4.3 %, 3/70), MT-TS1 (4.3 %, 3/70), MT-TK (7.1 %, 5/70) and MT-TE (5.7 %, 4/70) genes. We found that 15 variants were associated with hearing loss, including m.1555 A > G and m.1095 T > C. Additionally, we discovered three reported mitochondrial variants (m.676 G > A, m.7465 insC, and m.7474 A > G) newly correlated with hearing loss. Notably, certain pathogenic variants, such as m.1555 A > G, displayed non-consistent distributions among the multi-ethnic patients with hearing loss. Furthermore, the number of variants associated with hearing loss was higher in the Sinitic group (n = 181) and Tibeto-Burman group (n = 215) compared to the Kra-Dai group (n = 38) and Hmong-Mien group (n = 26).

Conclusions: This present study revealed the distribution of mitochondrial variants linked to hearing loss across various ethnic groups in Southwestern China. These data suggest a potential correlation between the distribution of mitochondrial variants associated with hearing loss and ethnic genetic backgrounds.

Keywords: Hearing loss; MT-RNR1; MT-TE; MT-TK; MT-TL1; MT-TS1; Multi-ethnic.