Neuromuscular DiseasesNeuromuscular DiseasesНервно-мышечные болезни2222-87212413-0443Publishing House ABV Press15410.17650/2222-8721-2016-6-2-47-51CLINICAL CASEКЛИНИЧЕСКИЙ РАЗБОРHereditary motor and sensory neuropathy, caused by mutations in the NEFL gene in a family from Karachaevo-CherkessiaНаследственная моторно-сенсорная нейропатия, обусловленная мутацией в гене NEFL, в семье из Карачаево-ЧеркессииDadaliE. L.ДадалиЕ. Л.
Russian Federation
genclinic@yandex.ruМаkаоvA. Kh.-M.МакаовА. Х.-М.
Russian Federation
GalkinaV. A.ГалкинаВ. А.
Russian Federation
KonovalovF. A.КоноваловФ. А.
Russian Federation
PolyakovA. V.ПоляковА. В.
Russian Federation
BulakhM. V.БулахМ. В.
Russian Federation
ZinchеnkоR. A.ЗинченкоР. А.
Russian Federation
Research Center of Medical GeneticsФГБНУ «Медико-генетический научный центр»1 Moskvorech’e St., Moscow, 115478, Russia N.I. Pirogov Russian National Research Medical University, Ministry of Health of RussiaРоссия, 115478, Москва, ул. Москворечье, 1 ГБОУ ВПО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России1 Ostrovityanova St., Moscow, 117997, RussiaРоссия, 117997, Москва, ул. Островитянова, 1Khabez Central District HospitalМБЛПУ «Хабезская центральная районная больница»6 Bol’nichnaya St., Khabez Aul, Khabez District, Karachai-Cherkess Republic, 369400, RussiaРоссия, Карачаево-Черкесская Республика, 369400, Хабезский район, аул Хабез, ул. Больничная, 61 Moskvorech’e St., Moscow, 115478, RussiaРоссия, 115478, Москва, ул. Москворечье, 1OOO “Genomed”ООО «Геномед»Build. 5, 8 Podol’skoye Shosse, Moscow, 115093, RussiaРоссия, 115093, Москва, Подольское шоссе, 8, корп. 5050720166247510507201605072016Copyright ©; 2016, Dadali E.L., Маkаоv A.K., Galkina V.A., Konovalov F.A., Polyakov A.V., Bulakh M.V., Zinchеnkо R.A.Copyright ©; 2016, Дадали Е.Л., Макаов А.Х., Галкина В.А., Коновалов Ф.А., Поляков А.В., Булах М.В., Зинченко Р.А.2016Dadali E.L., Маkаоv A.K., Galkina V.A., Konovalov F.A., Polyakov A.V., Bulakh M.V., Zinchеnkо R.A.Дадали Е.Л., Макаов А.Х., Галкина В.А., Коновалов Ф.А., Поляков А.В., Булах М.В., Зинченко Р.А.https://creativecommons.org/licenses/by/4.0https://nmb.abvpress.ru/jour/article/view/154

The clinical and genetic features of hereditary motor and sensory neuropathy (HMSN; Charcot–Marie–Tooth disease, CMT) caused by newly identified missense mutation s.65G>T (p.Pro22His) in NEFL gene located on the chromosome 8р21.2 are described. The disease was diagnosed in a large family from Ust-Dzhegutinsky district of the Karachay-Cherkess Republic with the segregation of the disease in four generations. The prevalence of the HMSN in that district was found to be 1:4340 persons, including 1:3376 among Karachays. The clinical picture of the disease was characterized by onset at the age of 11–14 years, weakness in foot muscles and steppage gait. The specific features in the majority of patients were the absence of major sensory disturbances, as well as long-term preserved distal arm muscles. Nerve conduction velocity in the median nerve varied from 30 to 42 m/s, which corresponds to values in patients with CMT2E, previously described.

В статье описаны клинико-генетические характеристики наследственной моторно-сенсорной нейропатии (НМСН, болезнь Шарко–Мари–Тута, БШМТ), обусловленной вновь выявленной миссенс-мутацией с.65G>T (p.Pro22His) в гене NEFL на хромосоме 8р21.2, у больных из семьи, проживающей в Усть-Джегутинском районе Карачаево-Черкесской Республики, с сегрегацией заболевания в 4 поколениях. Распространенность НМСН в обследованном районе составила 1:4340 человек, в том числе 1:3376 среди карачаевцев. Заболевание манифестировало в возрасте 11–14 лет с появления слабости стоп и формирования степпажной походки. Особенности клинических проявлений – отсутствие значимых расстройств чувствительности у большинства обследованных больных и длительная сохранность мышц дистальных отделов рук. Показатели скорости распространения возбуждения по срединному нерву колебались от 30 до 42 м/с, что соответствовало таковым у пациентов с БШМТ типа 2Е, описанным ранее.

hereditary motor and sensory neuropathyCharcot–Marie–Tooth disease type 2ЕKarachay-CherkessiaNEFLmissense mutation с.65G>Texsome sequencingнаследственная моторно-сенсорная нейропатияболезнь Шарко–Мари–Тута типа 2ЕКарачаево-ЧеркессияNEFLмиссенс-мутация с.65G>Tэкзомное секвенирование1. Harel T., Lupski J.R. Charcot–Marie– Tooth disease and pathways to molecular based therapies. Clin Genet 2014;86(5): 422–31. DOI: 10.1111/cge.12393. PMID: 24697164.Harel T., Lupski J.R. Charcot–Marie– Tooth disease and pathways to molecular based therapies. Clin Genet 2014;86(5): 422–31. DOI: 10.1111/cge.12393. PMID: 24697164.2. Saporta M.A., Shy M.E. Inherited peripheral neuropathies. Neurol Clin 2013;31(2):597–619. DOI: 10.1016/j.ncl.2013.01.009. PMID: 23642725.Saporta M.A., Shy M.E. Inherited peripheral neuropathies. Neurol Clin 2013;31(2):597–619. DOI: 10.1016/j.ncl.2013.01.009. PMID: 23642725.3. Timmerman V., Strickland A.V., Züchner S. Genetics of Charcot-Marie- Tooth (CMT) disease within the frame of the human genome project success. Genes (Basel) 2014;5(1):13–32. DOI: 10.3390/genes5010013. PMID: 24705285.Timmerman V., Strickland A.V., Züchner S. Genetics of Charcot-Marie- Tooth (CMT) disease within the frame of the human genome project success. Genes (Basel) 2014;5(1):13–32. DOI: 10.3390/genes5010013. PMID: 24705285.4. Dyck P.J., Lambert E.H. Lower motor and primary sensory neuron disease with peroneal muscular atrophy. Arch Neurol 1968;18(6):603–18. PMID: 4297451.Dyck P.J., Lambert E.H. Lower motor and primary sensory neuron disease with peroneal muscular atrophy. Arch Neurol 1968;18(6):603–18. PMID: 4297451.5. Dyck P.J., Chance P., Lebo R., Carney J.A. Hereditary motor and sensory neuropathies. In: Peripheral Neuropathy. By eds. P.J. Dyck, P.K. Thomas, J.W. Griffin et al. Philadelphia: W.B. Saunders Company, 1993. Pp. 1094–1136.Dyck P.J., Chance P., Lebo R., Carney J.A. Hereditary motor and sensory neuropathies. In: Peripheral Neuropathy. By eds. P.J. Dyck, P.K. Thomas, J.W. Griffin et al. Philadelphia: W.B. Saunders Company, 1993. Pp. 1094–1136.6. Harding A.E., Thomas P.K. The clinical features of hereditary motor and sensory neuropathy types I and II. Brain 1980;103(2):259–80. PMID: 7397478.Harding A.E., Thomas P.K. The clinical features of hereditary motor and sensory neuropathy types I and II. Brain 1980;103(2):259–80. PMID: 7397478.7. Shy M.E., Patzkо A. Axonal Charcot-Marie-Tooth disease. Curr Opin Neurol 2011;24(5):475–83. DOI: 10.1097/ WCO.0b013e32834aa331. PMID: 21892080.Shy M.E., Patzkо A. Axonal Charcot-Marie-Tooth disease. Curr Opin Neurol 2011;24(5):475–83. DOI: 10.1097/ WCO.0b013e32834aa331. PMID: 21892080.8. Rossor A.M., Polke J.M., Houlden H. Clinical implications of genetic advances in Charcot-Marie-Tooth disease. Nat Rev Neurol 2013;9(10):562–71. DOI: 10.1038/ nrneurol.2013. PMID: 24018473.Rossor A.M., Polke J.M., Houlden H. Clinical implications of genetic advances in Charcot-Marie-Tooth disease. Nat Rev Neurol 2013;9(10):562–71. DOI: 10.1038/ nrneurol.2013. PMID: 24018473.9. De Jonghe P., Mersiyanova I., Nelis E. et al. Further evidence that neurofilament light chain gene mutations can cause Charcot-Marie-Tooth disease type 2E. Ann Neurol 2001;49(2):245–9. PMID: 11220745.De Jonghe P., Mersiyanova I., Nelis E. et al. Further evidence that neurofilament light chain gene mutations can cause Charcot-Marie-Tooth disease type 2E. Ann Neurol 2001;49(2):245–9. PMID: 11220745.10. Mersiyanova I.V., Perepelov A.V., Polyakov A.V. et al. A new variant of Charcot-Marie- Tooth disease type 2 is probably the result of a mutation in the neurofilament-light gene. Am J Hum Genet 2000;67(1):37–46. PMID: 10841809.Mersiyanova I.V., Perepelov A.V., Polyakov A.V. et al. A new variant of Charcot-Marie- Tooth disease type 2 is probably the result of a mutation in the neurofilament-light gene. Am J Hum Genet 2000;67(1):37–46. PMID: 10841809.11. Georgiou D.M., Zidar J., Korosec M. et al. A novel NF-L mutation Pro22Ser is associated with CMT2 in a large Slovenian family. Neurogenetics 2002;4(2):93–6. PMID: 12481988.Georgiou D.M., Zidar J., Korosec M. et al. A novel NF-L mutation Pro22Ser is associated with CMT2 in a large Slovenian family. Neurogenetics 2002;4(2):93–6. PMID: 12481988.12. Fabrizi G.M., Cavallaro T., Angiari C. et al. Giant axon and neurofilament accumulation in Charcot–Marie–Tooth disease type 2E. Neurology 2004;62(8):1429–31. PMID: 15111691.Fabrizi G.M., Cavallaro T., Angiari C. et al. Giant axon and neurofilament accumulation in Charcot–Marie–Tooth disease type 2E. Neurology 2004;62(8):1429–31. PMID: 15111691.13. Jordanova A., De Jonghe P., Boerkoel C.F. et al. Mutations in the neurofilament light chain gene (NEFL) cause early onset severe Charcot–Marie–Tooth disease. Brain 2003;126(Pt 3):590–7. PMID: 12566280.Jordanova A., De Jonghe P., Boerkoel C.F. et al. Mutations in the neurofilament light chain gene (NEFL) cause early onset severe Charcot–Marie–Tooth disease. Brain 2003;126(Pt 3):590–7. PMID: 12566280.14. Аbe A., Numakura C., Saito K. et al. Neurofilament light chain polypeptide gene mutations in Charcot-Marie-Tooth disease: nonsense mutation probably causes a recessive phenotype. J Hum Genet 2009;54(2):94–7. DOI: 10.1038/jhg.2008.13. PMID: 19158810.Аbe A., Numakura C., Saito K. et al. Neurofilament light chain polypeptide gene mutations in Charcot-Marie-Tooth disease: nonsense mutation probably causes a recessive phenotype. J Hum Genet 2009;54(2):94–7. DOI: 10.1038/jhg.2008.13. PMID: 19158810.15. Yum S.W., Zhang J., Mo K. et al. A novel recessive NEFL mutation causes a severe, early-onset axonal neuropathy. Ann Neurol 2009;66(6):759–70. DOI: 10.1002/ana.21728.PMID: 20039262.Yum S.W., Zhang J., Mo K. et al. A novel recessive NEFL mutation causes a severe, early-onset axonal neuropathy. Ann Neurol 2009;66(6):759–70. DOI: 10.1002/ana.21728.PMID: 20039262.16. Agrawal P.B., Joshi M., Marinakis N.S. et al. Expanding the phenotype associated with the NEFL mutation: neuromuscular disease in a family with overlapping myopathic and neurogenic findings. JAMA Neurol 2014;71(11):1413–20. DOI: 10.1001/jamaneurol.2014.1432. PMID: 25264603.Agrawal P.B., Joshi M., Marinakis N.S. et al. Expanding the phenotype associated with the NEFL mutation: neuromuscular disease in a family with overlapping myopathic and neurogenic findings. JAMA Neurol 2014;71(11):1413–20. DOI: 10.1001/jamaneurol.2014.1432. PMID: 25264603.17. Boerkoel C.F., Takashima H., Lupski J.R. The genetic convergence of Charcot–Marie– Tooth disease types 1 and 2 and the role of genetics in sporadic neuropathy. Curr Neurol Neurosci Rep 2002;2(1):70–7. PMID: 11898586.Boerkoel C.F., Takashima H., Lupski J.R. The genetic convergence of Charcot–Marie– Tooth disease types 1 and 2 and the role of genetics in sporadic neuropathy. Curr Neurol Neurosci Rep 2002;2(1):70–7. PMID: 11898586.