Neuromuscular DiseasesNeuromuscular DiseasesНервно-мышечные болезни2222-87212413-0443Publishing House ABV Press28610.17650/2222-8721-2018-8-2-75-83CLINICAL CASEКЛИНИЧЕСКИЙ РАЗБОРA case of hereditary motor and sensory neuropathy type IVA with unusual genealogyСлучай наследственной моторной сенсорной нейропатии IVА типа с необычной родословнойhttps://orcid.org/0000-0002-8886-5222KurbatovS. A.КурбатовС. А.
Russian Federation

5A Lenina Ploshchad’, Voronezh 394018;  

Build. 2, 17 Krzhizhanovskogo St., Moscow 117258

394018 Воронеж, пл. Ленина, 5А; 117258 Москва, ул. Кржижановского, 17/2

https://orcid.org/0000-0002-0050-6947MilovidovaT. B.МиловидоваТ. Б.
Russian Federation

1 Moskvorech’e St., Moscow 115478

115478 Москва, ул. Москворечье, 1

https://orcid.org/0000-0003-4903-7886FedotovV. P.ФедотовВ. П.
Russian Federation

151 Moskovskiy Prospekt, Voronezh 394066

394066 Воронеж, Московский проспект, 151

https://orcid.org/0000-0001-7023-7378MurtazinaA. F.МуртазинаА. Ф.
Russian Federation

Build. 2, 17 Krzhizhanovskogo St., Moscow 117258

Айсылу Фанзировна Муртазина

117258 Москва, ул. Кржижановского, 17/2

aysylumurtazina@gmail.comhttps://orcid.org/0000-0002-8949-0581RudenskayaG. E.РуденскаяГ. Е.
Russian Federation

1 Moskvorech’e St., Moscow 115478

115478 Москва, ул. Москворечье, 1

https://orcid.org/0000-0003-4905-1303ShchaginaO. A.ЩагинаО. А.
Russian Federation

1 Moskvorech’e St., Moscow 115478

115478 Москва, ул. Москворечье, 1

https://orcid.org/0000-0002-0105-1833PolyakovA. V.ПоляковА. В.
Russian Federation

1 Moskvorech’e St., Moscow 115478

115478 Москва, ул. Москворечье, 1

Voronezh Regional Clinical Consulting and Diagnostic CenterАУЗ ВО «Воронежский областной клинический консультативно-диагностический центр»Association of Neuromuscular Disorders Specialists, Medical Center “Practical Neurology”Региональная общественная организация «Общество специалистов по нервно-мышечным болезням», Медицинский центр «Практическая неврология»Research Center of Medical GeneticsФГБНУ «Медико-генетический научный центр»Voronezh Regional Clinical Hospital No. 1БУЗ ВО «Воронежская областная клиническая больница № 1»200720188275832007201820072018Copyright ©; 2018, Kurbatov S.A., Milovidova T.B., Fedotov V.P., Murtazina A.F., Rudenskaya G.E., Shchagina O.A., Polyakov A.V.Copyright ©; 2018, Курбатов С.А., Миловидова Т.Б., Федотов В.П., Муртазина А.Ф., Руденская Г.Е., Щагина О.А., Поляков А.В.2018Kurbatov S.A., Milovidova T.B., Fedotov V.P., Murtazina A.F., Rudenskaya G.E., Shchagina O.A., Polyakov A.V.Курбатов С.А., Миловидова Т.Б., Федотов В.П., Муртазина А.Ф., Руденская Г.Е., Щагина О.А., Поляков А.В.https://creativecommons.org/licenses/by/4.0https://nmb.abvpress.ru/jour/article/view/286

Background. Hereditary motor and sensory neuropathies (HMSN) are a genetically diverse group of disorders of the peripheral nerves characterized by gradual development of weakness, muscular hypo-/atrophy, sensory disturbances in distal areas of the extremities. Currently among the recessive forms, the most prevalent HMSN is associated with the ganglioside-induced differentiation associated-protein 1 (GDAP1) gene (GDAP1-HMSN).

The objective is to present an observation of a family case of HMSN type IVA with unusual genealogy.

Materials and methods. Clinical, electrophysiological, and genetic characteristics of a Russian family with GDAP1-HMSN were examined.

Results. We describe a family with autosomal recessive HMSN and unusual genealogy due to homozygous and compound heterozygous mutations of GDAP1.

Conclusion. The particularity of the described family case is the unusual genealogy with the patients in two non-consecutive generations. This type of inheritance is caused by presence of mutations in compound heterozygous state in the proband's grandson which was confirmed by genetic analysis. The presented case demonstrates the importance and necessity of full analysis of the GDAP1 gene or identification of 2 mutations in trans-position in the proband and subsequent assessment of possible risks for future generations. Multiple stroke-like episodes in the 2 affected members of the family are described that have not been previously reported for GDAP1-HMSN. Stroke has been presented in HMSN associated with mitofusin-2 gene which also as GDAP1, affects mitochondrial function in the neurons.

hereditary motor and sensory neuropathyGDAP1 generecessive inheritancecerebral accidentнаследственная моторная сенсорная нейропатияген GDAP1рецессивный тип наследованияострое нарушение мозгового кровообращения2nd Workshop of the European CMT Consortium: 53rd ENMC International Workshop on Classification and Diagnostic Guidelines for Charcot–Marie–Tooth Type 2 (CMT2–HMSN II) and Distal Hereditary Motor Neuropathy (Distal HMN–Spinal CMT). Neuromuscular Disorders 1998(8):426–31. PMID: 9713862.Braathen G.J. Genetic epidemiology of Charcot–Marie–Tooth disease. Acta Neurol Scand Suppl 2012;(193):iv–22. DOI: 10.1111/ane.12013. PMID: 23106488.Dyck P.J., Lambert E.H. Lower motor and primary sensory neuron diseases with peroneal muscular atrophy. I. Neurologic, genetic, and electrophysiologic findings in hereditary polyneuropathies. Arch Neurol 1968;18(6):603–18. PMID: 4297451.Nicholson G., Myers S. Intermediate forms of Charcot–Marie–Tooth neuropathy: a review. Neuromolecular Med 2006;8(1–2):123–30. DOI: 10.1385/NMM:9:1. PMID: 16775371.Tazir M., Bellatache M., Nouioua S., Vallat J.M. Autosomal recessive Charcot–Marie–Tooth disease: from genes to phenotypes. J Peripher Nerv Syst 2013;18(2):113–29. DOI: 10.1111/jns5.12026. PMID: 23781959.Shchagina O.A., Dadali E.L., Fedotov V.P. et al. Hereditary motor and sensory neuropathy type 4A. Zhurnal nevrologii i psikhiatrii = Journal of Neurology and Psychiatry 2010;110(5):13–6. (In Russ).Щагина О.А., Дадали Е.Л., Федотов В.П. и др. Наследственная моторно-сенсорная полинейропатия типа 4А. Журнал неврологии и психиатрии 2010;110(5):13–6.Shchagina O.A., Milovidova T.B., Bulakh M.V., Polyakov A.V. The study of autosomal recessive CMTdisease with using a new medical technologies “One tube detection system for most common recessive CMT-mutation”. Meditsinskaya genetika = Medical Genetics 2016;15(3):35–9. (In Russ).Щагина О.А., Миловидова Т.Б., Булах М.В., Поляков А.В. Исследование рецессивных форм НМСН у российских больных с использованием новой медицинской технологии «Система детекции в одной пробирке частых мутаций при рецессивных наследственных моторно-сенсорных нейропатиях». Медицинская генетика 2016;15(3):35–9.Pezzini I., Geroldi A., Capponi S. et al. GDAP1 mutations in Italian axonal Charcot-Marie-Tooth patients: phenotypic features and clinical course. Neuromuscul Disord 2016;26(1):26–32. DOI: 10.1016/j.nmd.2015.09.008. PMID: 26525999.Marttila M., Kytövuori L., Helisalmi S. et al. Molecular epidemiology of Charcot– Marie–Tooth disease in Northern Ostrobothnia, Finland: a population-based study. Neuroepidemiology 2017;49 (1–2):34–9. DOI: 10.1159/000478860. PMID: 28810241.Eggermann K., Gess B., Häusler M. et al. Hereditary neuropathies: clinical presentation and genetic panel diagnosis. Deutsches Ärzteblatt Int 2018;115(6): 91–7. DOI:10.3238/arztebl.2018.0091.van Paassen B.W., Bronk M., Verhamme C. et al. Pseudodominant inheritance pattern in a family with CMT2 caused by GDAP1 mutations. J Peripher Nerv Syst 2017;22(4):464–7. DOI: 10.1111/ jns.12236. PMID: 28837237.Bird T.D. GDAP1-related hereditary motor and sensory neuropathy. Gene Reviews. University of Washington, Seattle; 1993–2018.Moroni I., Morbin M., Milani M. et al. Novel mutations in the GDAP1 gene in patients affected with early-onset axonal Charcot–Marie–Tooth type 4A. Neuromuscul Disord 2009;19(7):476–80. DOI: 10.1016/j.nmd.2009.04.014. PMID: 19500985.Niemann A., Ruegg M., La Padula V. et al. Ganglioside-induced differentiation associated protein 1 is a regulator of the mitochondrial network: new implications for Charcot–Marie–Tooth disease. J Cell Biol 2005;170(7):1067–78. DOI: 10.1083/jcb.200507087. PMID: 16172208.Baxter R.V., Ben Othmane K., Rochelle J.M. et al. Ganglioside-induced differentiationassociated protein-1 is mutant in Charcot–Marie–Tooth disease type 4A/8q21. Nature Genet 2002;30(1):21–2. DOI: 10.1038/ng796. PMID: 11743579.Cuesta A., Pedrola L., Sevilla T. et al. The gene encoding ganglioside-induced differentiation-associated protein 1 is mutated in axonal Charcot–Marie–Tooth type 4A disease. Nature Genet 2002;30(1):22–4. DOI: 10.1038/ng798. PMID: 11743580.Claramunt R., Pedrola L., Sevilla T. et al. Genetics of Charcot–Marie–Tooth disease type 4A: mutations, inheritance, phenotypic variability, and founder effect. J Med Gene 2005;42(4):358–65. DOI: 10.1136/jmg.2004.022178. PMID: 15805163.Рыжкова О.П., Кардымон О.Л., Прохорчук Е.Б. и др. Руководство по интерпретации данных, полученных методами массового параллельного секвенирования (MPS). Медицинская генетика 2017;(7):4–17. [Ryzhkova O.P., Kardymon O.L., Prokhorchuk E.B. et al. Guidelines for the interpretation of massive parallel sequencing variants. Meditsinskaya genetika = Medical Genetics 2017;(7):4–17. (In Russ)].Kabzińska D., Kotruchow K., Cegielska J. et al. A severe recessive and a mild dominant form of Charcot–Marie–Tooth disease associated with a newly identified Glu222Lys GDAP1 gene mutation. Acta Biochim Pol 2014;61(4):739–44. PMID: 25337607.Zimoń M., Baets J., Fabrizi G.M. et al. Dominant GDAP1 mutations cause predominantly mild CMT phenotypes. Neurology 2011;77(6):540–8. DOI: 10.1212/WNL.0b013e318228fc70. PMID: 21753178.Sivera R., Espinós C., Vílchez J.J. et al. Phenotypical features of the p.R120W mutation in the GDAP1 gene causing autosomal dominant Charcot–Marie–Tooth disease. J Peripher Nerv Syst 2010;15(4):334–44. DOI: 10.1111/j.1529-8027.2010.00286.x. PMID: 21199105.Kabzińska D., Strugalska-Cynowska H., Kostera-Pruszczyk A. et al. L239F founder mutation in GDAP1 is associated with a mild Charcot–Marie–Tooth type 4C4 (CMT4C4) phenotype. Neurogenetics 2010;11(3):357–66. DOI: 10.1007/s10048-010-0237-6. PMID: 20232219.Sevilla T., Cuesta A., Chumillas M.J. et al. Clinical, electrophysiological and morphological findings of Charcot–Marie– Tooth neuropathy with vocal cord palsy and mutations in the GDAP1 gene. Brain 2003;126(Pt 9):2023–33. DOI: 10.1093/brain/awg202. PMID: 12821518.Rodondi N., Locatelli I., Aujesky D. et al. Framingham risk score and alternatives for prediction of coronary heart disease in older adults. 2012;7(3):e34287. DOI: 10.1371/journal.pone.0034287.DiMauro S., Hirano M. MELAS. 2001 GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993– 2018. PMID: 20301411.Jahani-Asl A., Cheung E.C., Neuspiel M. et al. Mitofusin 2 protects cerebellar granule neurons against injury induced cell death. J Biol Chem 2007;282(33): 23788–98. DOI: 10.1074/jbc. M703812200. PMID: 17537722.Chung K.W., Cho S.Y., Hwang S.J. et al. Early-onset stroke associated with a mutation in mitofusin 2. Neurology 2008;70(21):2010–1. DOI: 10.1212/01.wnl.0000312513.96457.7a. PMID: 18490623.Procaccio V., Bris C., Chao de la Barca J.M. et al. Perspectives of drug-based neuroprotection targeting mitochondria. Rev Neurol (Paris) 2014;170(5):390–400. DOI: 10.1016/j.neurol.2014.03.005. PMID: 24792485.