Molecular Biology Reports

, Volume 47, Issue 2, pp 1331–1337 | Cite as

HINT1 gene pathogenic variants: the most common cause of recessive hereditary motor and sensory neuropathies in Russian patients

  • O. A. Shchagina
  • T. B. Milovidova
  • A. F. MurtazinaEmail author
  • G. E. Rudenskaya
  • S. S. Nikitin
  • E. L. Dadali
  • A. V. Polyakov
Original Article


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.


Hereditary motor and sensory neuropathy HINT1 gene Axonopathy Neuromyotonia Distal motor neuropathy Charcot–Marie–Tooth disease 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study was approved by the local ethics committee of the Federal State Budgetary Institution “Research Centre for Medical Genetics” (the approval number 2018-5/4).

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

11033_2019_5238_MOESM1_ESM.docx (457 kb)
Supplementary file1 (DOCX 457 kb)


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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Laboratory of DNA Diagnostics, Laboratory of Molecular Genetic Diagnosis №1 of Research Centre for Medical GeneticsMoscowRussia
  2. 2.Laboratory of DNA Diagnostics of Research Centre for Medical GeneticsMoscowRussia
  3. 3.Research Centre for Medical GeneticsMoscowRussia
  4. 4.Scientific and Medical Department of Research Centre for Medical GeneticsMoscowRussia
  5. 5.Association of Neuromuscular Disorders SpecialistsMoscowRussia

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