中国西南地区与听力损失相关的线粒体 MT-RNR1、MT-TL1、MT-TS1、MT-TK 和 MT-TE 基因变异的分布。
Distribution of mitochondrial MT-RNR1, MT-TL1, MT-TS1, MT-TK and MT-TE genes variants associated with hearing loss in Southwestern China.
机构信息
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.
The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China.
出版信息
Int J Pediatr Otorhinolaryngol. 2024 Jun;181:111979. doi: 10.1016/j.ijporl.2024.111979. Epub 2024 May 9.
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.
背景
母系遗传性听力损失与线粒体基因有关，包括 MT-RNR1、MT-TL1、MT-TS1、MT-TK 和 MT-TE。在这些基因中，MT-RNR1 是与氨基糖苷类耳毒性和非综合征性听力损失相关的致病性变异的热点。然而，这些基因中的变异的频率和谱，特别是在中国西南部的多民族听力损失患者中，仍然不完全清楚。
方法
在这项研究中，我们招募了来自中国西南部不同民族背景（汉族、彝族、傣族、哈尼族等）的 460 名听力损失患者。使用下一代测序分析线粒体 MT-RNR1、MT-TL1、MT-TS1、MT-TK 和 MT-TE 基因。随后，采用生物信息学方法评估所鉴定的变异。
结果
在听力损失患者中，我们在 MT-RNR1（78.6%，55/70）、MT-TL1（4.3%，3/70）、MT-TS1（4.3%，3/70）、MT-TK（7.1%，5/70）和 MT-TE（5.7%，4/70）基因中发现了 70 个变异。我们发现 15 个变异与听力损失有关，包括 m.1555A>G 和 m.1095T>C。此外，我们发现了三个新报道的与听力损失相关的线粒体变异（m.676G>A、m.7465insC 和 m.7474A>G）。值得注意的是，某些致病性变异，如 m.1555A>G，在多民族听力损失患者中的分布并不一致。此外，与听力损失相关的变异数量在汉藏语系组（n=181）和侗傣语系组（n=215）高于高棉语系组（n=38）和苗瑶语系组（n=26）。
结论
本研究揭示了中国西南部不同民族群体中与听力损失相关的线粒体变异的分布。这些数据表明，与听力损失相关的线粒体变异的分布与种族遗传背景之间存在潜在的相关性。
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