Neuromuscular DiseasesNeuromuscular DiseasesНервно-мышечные болезни2222-87212413-0443Publishing House ABV Press21310.17650/2222-8721-2017-7-3-47-55ORIGINAL REPORTSОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯClinical and genetic characteristics of autosomal recessive axonal neuropathy with neuromyotonia in Russian patientsКлинико-генетические характеристики аутосомно-рецессивной аксональной нейропатии с нейромиотонией у больных из РоссииDadaliE. L.ДадалиЕ. Л.
Russian Federation
NikitinS. S.НикитинС. С.
Russian Federation
KurbatovS. A.КурбатовС. А.
Russian Federation
MurtazinaA. F.МуртазинаА. Ф.
Russian Federation
SharkovaI. V.ШарковаИ. В.
Russian Federation
ShchaginaO. A.ЩагинаО. А.
Russian Federation
KonovalovF. A.КоноваловФ. А.
Russian Federation
Research Center of Medical GeneticsФБГНУ «Медико-генетический научный центр»Medical Center “Practical Neurology”, Association of Neuromuscular Disorders SpecialistsРегиональная общественная организация «Общество специалистов по нервно-мышечным болезням», Медицинский центр «Практическая неврология»Voronezh Regional Clinical Consultative and Diagnostic CentreАУЗ ВО «Воронежский областной клинический консультативно-диагностический центр»OOO “Genomed”ООО «Геномед»071120177347550711201707112017Copyright ©; 2017, Dadali E.L., Nikitin S.S., Kurbatov S.A., Murtazina A.F., Sharkova I.V., Shchagina O.A., Konovalov F.A.Copyright ©; 2017, Дадали Е.Л., Никитин С.С., Курбатов С.А., Муртазина А.Ф., Шаркова И.В., Щагина О.А., Коновалов Ф.А.2017Dadali E.L., Nikitin S.S., Kurbatov S.A., Murtazina A.F., Sharkova I.V., Shchagina O.A., Konovalov F.A.Дадали Е.Л., Никитин С.С., Курбатов С.А., Муртазина А.Ф., Шаркова И.В., Щагина О.А., Коновалов Ф.А.https://creativecommons.org/licenses/by/4.0https://nmb.abvpress.ru/jour/article/view/213

Introduction. Hereditary motor and sensory neuropathies are genetically heterogeneous group of disorders characterized by a progressive muscle weakness, atrophy of hand and leg muscles often associated with deformations, and mild to moderate sensory loss. Axonal neuropathy with neuromyotonia (AR-ANM) is one of the rarest autosomal recessive hereditary neuropathies. Materials and methods. Six (6) patients (4 men, 2 women) aged 14–40 years from unrelated families with suspicion of HMSN were examined clinically, neurophysiologically and using DNA analysis. Results. Neurophysiological examination revealed motor and sensory neuropathy with neuromyotonia signs in all patients. In all cases homozygous variant of recessive mutations с.110G/C (р.Arg37Pro) in the gene encoding the histidine triad nucleotide binding protein 1 (HINT1) has been revealed. Conclusion. There is the first description of the clinical and neurophysiological features of six patients with AR-ANM in Russia.

 

Введение. Наследственные моторно-сенсорные нейропатии (НМСН) – группа генетически гетерогенных болезней, характеризующихся прогрессирующей дистальной слабостью, гипо-/атрофией мышц стоп, кистей с последующей их деформацией, расстройствами чувствительности. Аксональная нейропатия в сочетании с нейромиотонией (АР-АНМ) считается одним из редких аутосомно-рецессивных вариантов НМСН. Материалы и методы. Клинически, нейрофизиологически и посредством ДНК-анализа обследованы 6 больных (4 мужчины, 2 женщины) в возрасте 14–40 лет из неродственных семей с предположительным диагнозом НМСН. Результаты. Нейрофизиологическое исследование у пациентов выявило моторную и сенсорную нейропатию в сочетании с нейромиотонией при исследовании мышц игольчатыми электродами. Молекулярно-генетическое исследование у всех пациентов обнаружило мутацию с.110G>C (р.Arg37Pro) в гомозиготном состоянии в гене HINT1. Заключение. Представлено первое в России описание клинических, нейрофизиологических и генетических особенностей 6 больных АР-АНМ.

 

distal hereditary motor neuropathyaxonal neuropathyneuromyotoniaHINT1дистальная наследственная моторная нейропатияаксональная нейропатиянейромиотонияHINT11. Lance J. W., Durke D., Pollard J. Neuromyotonia in the spinal form of Charcot – Marie – Tooth disease. Clin Exp Neurol 1979;16:49–56. PMID: 550956.Lance J. W., Durke D., Pollard J. Neuromyotonia in the spinal form of Charcot – Marie – Tooth disease. Clin Exp Neurol 1979;16:49–56. PMID: 550956.2. Hahn A. F., Parkes A. W., Bolton C. F., Stewart S. A. Neuromyotonia in hereditary motor neuropathy. J Neurol Neurosurg Psychiatry. 1991;54(3):230–5. DOI: 10.1136/jnnp.54.3.230. PMID: 1851512.Hahn A. F., Parkes A. W., Bolton C. F., Stewart S. A. Neuromyotonia in hereditary motor neuropathy. J Neurol Neurosurg Psychiatry. 1991;54(3):230–5. DOI: 10.1136/jnnp.54.3.230. PMID: 1851512.3. Zimoń M., Baets J., Almeida-Souza L. et al. Loss-of-function mutationsZimoń M., Baets J., Almeida-Souza L. et al. Loss-of-function mutationsin HINT1 cause axonal neuropathy with neuromyotonia. Nat Genet 2012;44(10):1080–3. DOI: 10.1038/ ng.2406. PMID: 22961002.4. Gilmour J., Liang N., Lowenstein J. M. Isolation, cloning and characterization of a low-molecular-mass purine nucleo-side- and nucleotide-binding protein. Biochem J 1997;326(Pt 2):471–7. PMID: 9291120.Gilmour J., Liang N., Lowenstein J. M. Isolation, cloning and characterization of a low-molecular-mass purine nucleo-side- and nucleotide-binding protein. Biochem J 1997;326(Pt 2):471–7. PMID: 9291120.5. Weiske J., Huber O. The histidine triad protein Hint1 triggers apoptosis independent of its enzymatic activity. J Biol Chem 2006;281(37):27356–66. DOI: 10.1074/jbc.M513452200. PMID: 16835243.Weiske J., Huber O. The histidine triad protein Hint1 triggers apoptosis independent of its enzymatic activity. J Biol Chem 2006;281(37):27356–66. DOI: 10.1074/jbc.M513452200. PMID: 16835243.6. Zimoń M., Battaloğlu E., Parman Y. et al. Unraveling the genetic landscape of auto-somal recessive Charcot–Marie–Tooth neuropathies using a homozygosity mapping approach. Neurogenetics 2015;16(1):33–42. DOI: 10.1007/s10048-014-0422-0. PMID: 25231362.Zimoń M., Battaloğlu E., Parman Y. et al. Unraveling the genetic landscape of auto-somal recessive Charcot–Marie–Tooth neuropathies using a homozygosity mapping approach. Neurogenetics 2015;16(1):33–42. DOI: 10.1007/s10048-014-0422-0. PMID: 25231362.7. Lassuthova P., Brozkova D. S., Krutova M. et al. Mutations in HINT1 are oneLassuthova P., Brozkova D. S., Krutova M. et al. Mutations in HINT1 are oneof the most frequent causes of hereditary neuropathy among Czech patients and neuromyotonia is rather an underdiag-nosed symptom. Neurogenetics 2015;16(1):43–54. DOI: 10.1007/s10048-014-0427-8. PMID: 25342199.8. Peeters K., Chamova T., Tournev I., Jordanova A. Axonal neuropathy with neuromyotonia: there is a HINT. Brain 2017;140 (4):868–77. DOI: 10.1093/brain/aww301. PMID: 28007994.Peeters K., Chamova T., Tournev I., Jordanova A. Axonal neuropathy with neuromyotonia: there is a HINT. Brain 2017;140 (4):868–77. DOI: 10.1093/brain/aww301. PMID: 28007994.9. Horga A., Cottenie E., Tomaselli P. J. et al. Absence of HINT1 mutations in a UK and Spanish cohort of patients with inherited neuropathies. J Neurol 2015;262(8):1984–6. DOI: 10.1007/s00415-015-7851-z. PMID: 26194197.Horga A., Cottenie E., Tomaselli P. J. et al. Absence of HINT1 mutations in a UK and Spanish cohort of patients with inherited neuropathies. J Neurol 2015;262(8):1984–6. DOI: 10.1007/s00415-015-7851-z. PMID: 26194197.10. Zhao H., Race V., Matthijs G. et al. Exome sequencing reveals HINT1 mutations as a cause of distal hereditary motor neuropathy. Eur J Hum Genet 2014;22(6):847–50. DOI: 10.1038/ ejhg.2013.231. PMID: 24105373.Zhao H., Race V., Matthijs G. et al. Exome sequencing reveals HINT1 mutations as a cause of distal hereditary motor neuropathy. Eur J Hum Genet 2014;22(6):847–50. DOI: 10.1038/ ejhg.2013.231. PMID: 24105373.11. Jerath N. U., Shy M. E., Grider T., Gutmann L. A case of neuromyotonia and axonalmotor neuropathy: a report of a HINT1 mutation in the United States. Muscle Nerve 2015;52(6):1110–3. DOI: 10.1002/mus.24774. PMID: 26182879.Jerath N. U., Shy M. E., Grider T., Gutmann L. A case of neuromyotonia and axonalmotor neuropathy: a report of a HINT1 mutation in the United States. Muscle Nerve 2015;52(6):1110–3. DOI: 10.1002/mus.24774. PMID: 26182879.12. Kucukali C. I., Kurtuncu M., Akcay H. I. et al. Peripheral nerve hyperexcitability syndromes. Rev Neurosci 2015;26 (2):239–51. PMID: 25719304. DOI:10.1515/revneuro-2014–0066.Kucukali C. I., Kurtuncu M., Akcay H. I. et al. Peripheral nerve hyperexcitability syndromes. Rev Neurosci 2015;26 (2):239–51. PMID: 25719304. DOI:10.1515/revneuro-2014–0066.13. Caetano J. S., Costa C., Baets J. et al. Autosomal recessive axonal neuropathy with neuromyotonia: a rare entity. Pediatr Neurol 2014;50(1): 104–7. DOI: 10.1016/ j.pediatrneurol. 2013.08.028. PMID: 24131582.Caetano J. S., Costa C., Baets J. et al. Autosomal recessive axonal neuropathy with neuromyotonia: a rare entity. Pediatr Neurol 2014;50(1): 104–7. DOI: 10.1016/ j.pediatrneurol. 2013.08.028. PMID: 24131582.14. Su T., Suzui M., Wang L. et al. Deletion of histidine triad nucleotide-binding protein 1/PKC-interacting protein in mice enhances cell growth and carcinogenesis. Proc Natl Acad Sci U S A 2003;100(13): 7824–9. DOI: 10.1073/pnas.1332160100. PMID: 12810953.Su T., Suzui M., Wang L. et al. Deletion of histidine triad nucleotide-binding protein 1/PKC-interacting protein in mice enhances cell growth and carcinogenesis. Proc Natl Acad Sci U S A 2003;100(13): 7824–9. DOI: 10.1073/pnas.1332160100. PMID: 12810953.15. Seburn K. L., Morelli K. H., Jordanova A., Burgess R. W. Lack of neuropathy related phenotypes in HINT1 knockout mice. J Neuropathol Exp Neurol 2014;73(7): 693–701. DOI:10.1097/NEN. 0000000000000085. PMID: 24918641.Seburn K. L., Morelli K. H., Jordanova A., Burgess R. W. Lack of neuropathy related phenotypes in HINT1 knockout mice. J Neuropathol Exp Neurol 2014;73(7): 693–701. DOI:10.1097/NEN. 0000000000000085. PMID: 24918641.16. Rauchenzauner M., Frühwirth M., Hecht M. et al. A novel variantRauchenzauner M., Frühwirth M., Hecht M. et al. A novel variantin the HINT1 gene in a girl with autosomal recessive axonal neuropathy with neuromyotonia: thorough neurological examination gives the clue. Neuropediatrics 2016;47(2):119–22. DOI: 10.1055/s-0035-1570493. PMID: 26760849.17. Boaretto F., Cacciavillani M., Mostacciuolo M. L. et al. Novel loss-of-function mutation of the HINT1 gene in a patient with distal motor axonal neuropathy without neuromyotonia. Muscle Nerve 2015;52(4): 688–9. DOI: 10.1002/mus.24720. PMID: 26059562.Boaretto F., Cacciavillani M., Mostacciuolo M. L. et al. Novel loss-of-function mutation of the HINT1 gene in a patient with distal motor axonal neuropathy without neuromyotonia. Muscle Nerve 2015;52(4): 688–9. DOI: 10.1002/mus.24720. PMID: 26059562.18. Chou T. F., Sham Y. Y., Wagner C. R. Impact of the C-terminal loop of histidine triad nucleotide binding protein1 (Hint1) on substrate specificity. Biochemistry 2007;46 (45):13074–9. DOI: 10.1021/bi701244h. PMID: 17939685.Chou T. F., Sham Y. Y., Wagner C. R. Impact of the C-terminal loop of histidine triad nucleotide binding protein1 (Hint1) on substrate specificity. Biochemistry 2007;46 (45):13074–9. DOI: 10.1021/bi701244h. PMID: 17939685.