Pathogenic variants in the HINT1 gene lead to hereditary axonopathy with neuromyotonia. However, many studies show that neuromyotonia may remain undiagnosed, while axonopathy is the major clinical finding. The most common cause of neuromyotonia and axonopathy, especially in patients of Slavic origin, is a c.110G>C (p.Arg37Pro) pathogenic variant in homozygous or compound heterozygous state. In this study, we analyzed a peripheral neuropathy caused by pathogenic variants in the HINT1 gene and evaluated its contribution to the hereditary neuropathy structure. The studied group included 1596 non-related families diagnosed with hereditary motor and sensory neuropathy (HMSN). The results show that HINT1 gene pathogenic variants make a significant contribution to the hereditary neuropathy epidemiology in Russian patients. They account for at least 1.9% of all HMSN cases and 9% of axonopathy cases. The most common HINT1 pathogenic variant in Russian patients is the c.110G>C (p.Arg37Pro) substitution. Its allelic frequency is 0.2% (95% CI 0.19-0.21%), carrier frequency is 1 in 250 people in Russian Federation, and the estimated disease incidence is 1 in 234,000 individuals. It was determined that the cause of this pathogenic variant's prevalence is the founder effect.

中文翻译：

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HINT1基因致病变异：俄罗斯患者隐性遗传性运动和感觉神经病的最常见原因。

HINT1基因的致病性变异导致遗传性轴索病并伴有神经强直性。然而，许多研究表明，神经肌强直可能仍未得到诊断，而轴突病是主要的临床发现。神经肌强直和轴突病的最常见原因，特别是在斯拉夫血统的患者中，是纯合或复合杂合状态的c.110G> C（p.Arg37Pro）致病变异。在这项研究中，我们分析了由HINT1基因致病性变异引起的周围神经病变，并评估了其对遗传性神经病变结构的贡献。研究组包括1596个被诊断为遗传性运动和感觉神经病（HMSN）的无关家庭。结果表明，HINT1基因致病变异对俄罗斯患者的遗传性神经病流行病学做出了重大贡献。它们至少占1。在所有HMSN病例中占9％，在轴突病变病例中占9％。在俄罗斯患者中最常见的HINT1致病变异是c.110G> C（p.Arg37Pro）替代。它的等位基因频率为0.2％（95％CI 0.19-0.21％），携带者频率在俄罗斯联邦为250人中的1人，估计的疾病发病率为234,000人中的1人。已确定该致病变异流行的原因是创始人效应。