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.
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.
摘要：
背景：母体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,已知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变体的热点。然而,这些基因变异的频率和频谱，特别是来自中国西南部的多民族听力损失患者，仍然没有完全理解。
方法：在本研究中，我们招募了460名来自不同种族背景的听力损失患者(汉族，Yi,戴,哈尼,等。)在中国西南部。使用下一代测序来分析线粒体MT-RNR1、MT-TL1、MT-TS1、MT-TK和MT-TE基因。随后，使用生物信息学方法来评估所鉴定的变体。
结果：在听力损失患者中，我们在MT-RNR1中鉴定出70个变体(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。我们发现15种变异与听力损失有关,包括m.1555A>G和m.1095T>C。此外，我们发现了三个报道的线粒体变异(m.676G>A，m.7465insC,和m.7474A>G）与听力损失新相关。值得注意的是,某些致病变种，例如m.1555A>G，在听力损失的多种族患者中表现出不一致的分布。此外，与Kra-Dai组(n=38)和Hmong-Mien组(n=26)相比,Sinitic组(n=181)和Tibeto-Burman组(n=215)与听力损失相关的变异数量更高.
结论：本研究揭示了在中国西南部不同民族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。
方法：在本研究中，我们招募了460名来自不同种族背景的听力损失患者(汉族，Yi,戴,哈尼,等。)在中国西南部。使用下一代测序来分析线粒体MT-RNR1、MT-TL1、MT-TS1、MT-TK和MT-TE基因。随后，使用生物信息学方法来评估所鉴定的变体。
结果：在听力损失患者中，我们在MT-RNR1中鉴定出70个变体(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。我们发现15种变异与听力损失有关,包括m.1555A>G和m.1095T>C。此外，我们发现了三个报道的线粒体变异(m.676G>A，m.7465insC,和m.7474A>G）与听力损失新相关。值得注意的是,某些致病变种，例如m.1555A>G，在听力损失的多种族患者中表现出不一致的分布。此外，与Kra-Dai组(n=38)和Hmong-Mien组(n=26)相比,Sinitic组(n=181)和Tibeto-Burman组(n=215)与听力损失相关的变异数量更高.
结论：本研究揭示了在中国西南部不同民族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。
