, Volume 16, Issue 1, pp 43–54 | Cite as

Mutations in HINT1 are one of the most frequent causes of hereditary neuropathy among Czech patients and neuromyotonia is rather an underdiagnosed symptom

  • P. LaššuthováEmail author
  • D. Šafka Brožková
  • M. Krůtová
  • J. Neupauerová
  • J. Haberlová
  • R. Mazanec
  • N. Dvořáčková
  • Z. Goldenberg
  • P. Seeman
Original Article


Mutations in the HINT1 gene were recently discovered as being the major cause of autosomal recessive axonal neuropathy with neuromyotonia. This combination was clinically recognized and described previously in a few reports but is generally unknown. We aimed to establish the importance of HINT1 mutations as the cause of hereditary neuropathy and particularly hereditary motor neuropathy/axonal Charcot-Marie-Tooth (HMN/CMT2) among Czech patients. Overall, mutations in the HINT1 gene seem to be a surprisingly frequent cause of inherited neuropathy in our group of patients. Biallelic pathogenic mutations were found in 21 patients from 19 families. The prevalent mutation in the Czech population is the p.R37P (95 % of pathogenic alleles). Clinically, all patients with biallelic mutations presented with early onset of symptoms at the end of the first decade. Foot/toe extension weakness to plegia was present in almost all patients. Neuromyotonia was present in all but two patients. However, it had been properly recognized in only three patients prior to molecular genetic diagnosis. HINT1 mutations seem to be one of the most frequent causes of inherited neuropathy and are probably the most frequent cause of HMN in Czech patients. We suggest all HMN/CMT2 patients be tested for the presence of the prevalent mutation, the p.R37P.


HINT1 Hereditary motor neuropathy CMT2 Neuromyotonia 



We deeply thank the patients and their families for participating in the study. We thank all the referring clinical neurologists and clinical geneticist for sending patients for DNA testing to our laboratory. This study is supported by IGA MH CR No. NT 14348-3 and MH CZ—DRO, University Hospital Motol, Prague, Czech Republic 00064203.

Ethical standards

Experiments comply with the current laws of the country of origin.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

10048_2014_427_MOESM1_ESM.pdf (10 kb)
Table S1 Custom TaqMan® SNP Genotyping Assays designed by Applied Biosystems (AppliedBiosystem, LifeTechnologies). Sequences of Primers and TaqMan Probes. (PDF 10 kb)
10048_2014_427_Fig9_ESM.gif (676 kb)
Figure S2

Patient 11 at the age of 61. Calf muscle atrophy, foot plegia, genua recurvata. (GIF 675 kb)

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High Resolution Image (TIFF 33166 kb)
10048_2014_427_Fig10_ESM.gif (672 kb)
Figure S3

Patient 17 at the age of 16. Muscles of hips and calves are evolved. Pedes planovalgi are present. Active foot extension is possible to 90°. (GIF 671 kb)

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High Resolution Image (TIFF 33166 kb)
10048_2014_427_Fig11_ESM.gif (980 kb)
Figure S4

Patient 19 at the age of 14. She is able to squat, walk on toes, but unable to walk on heels. Steppage gait and foot extension plegia are present. (GIF 980 kb)

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High Resolution Image (TIFF 33166 kb)
Video S5

Neuromyotonia (MP4 5826 kb)

Video S6

Neuromyotonia (MP4 2421 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • P. Laššuthová
    • 1
    Email author
  • D. Šafka Brožková
    • 1
  • M. Krůtová
    • 1
  • J. Neupauerová
    • 1
  • J. Haberlová
    • 2
  • R. Mazanec
    • 3
  • N. Dvořáčková
    • 4
  • Z. Goldenberg
    • 5
  • P. Seeman
    • 1
  1. 1.DNA Laboratory, Department of Paediatric Neurology, 2nd Faculty of MedicineCharles University in Prague and University Hospital MotolPragueCzech Republic
  2. 2.Department of Paediatric Neurology, 2nd Faculty of MedicineCharles University in Prague and University Hospital MotolPragueCzech Republic
  3. 3.Department of NeurologyCharles University 2nd Medical School and University Hospital MotolPragueCzech Republic
  4. 4.Department of Medical GeneticsUniversity Hospital OstravaOstravaCzech Republic
  5. 5.1st Department of Neurology, University Hospital - Stare Mesto and Medical FacultyComenius University BratislavaBratislavaSlovakia

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