Neuromuscular DiseasesNeuromuscular DiseasesНервно-мышечные болезни2222-87212413-0443Publishing House ABV Press14110.17650/2222-8721-2016-6-1-82-88CLINICAL CASEКЛИНИЧЕСКИЙ РАЗБОРMiyoshi myopathy: diagnosis of a familial case of dysferlinopathyМиопатия Миоши: диагностика семейного случая дисферлинопатииFedotovV. P.ФедотовВ. П.
Russian Federation
fed_val@list.ruRyzhkovaO. P.РыжковаО. П.
Russian Federation
PolyakovA. V.ПоляковА. В.
Russian Federation
Voronezh Regional Clinical Hospital OneБУЗ ВО «Воронежская областная клиническая больница No 1»151 Moskovskiy Prospekt, Voronezh, 394066, RussiaРоссия, 394066, Воронеж, Московский просп., 151Research Center of Medical Genetics1 Moskvorech’e St., Moscow, 115522, RussiaФГБНУ «Медико-генетический научный центр»Россия, 115522, Москва, ул. Москворечье, 1Research Center of Medical Genetics1 Moskvorech’e St., Moscow, 115522, RussiaФГБНУ «Медико-генетический научный центр»Россия, 115522, Москва, ул. Москворечье, 1290320166182882903201629032016Copyright ©; 2016, Fedotov V.P., Ryzhkova O.P., Polyakov A.V.Copyright ©; 2016, Федотов В.П., Рыжкова О.П., Поляков А.В.2016Fedotov V.P., Ryzhkova O.P., Polyakov A.V.Федотов В.П., Рыжкова О.П., Поляков А.В.https://creativecommons.org/licenses/by/4.0https://nmb.abvpress.ru/jour/article/view/141

Miyoshi myopathy (MM) is a rare distal form of limb-girdle muscular dystrophies characterized by weakness primarily affecting the calves in adolescence or young adulthood, with slow progression, the ascending pattern of involvement of muscle groups in an atrophic process, and with obvious clinical polymorphism at onset (3 allelic variants are described). In MM, hypercreatine phosphatemia is noted to be 20– 50 times the normal blood concentrations. MM is referred to the dysferlinopathies with different mutations in the DYSF gene. 

In that manuscript we describe a 20-year familial case of 2 brothers with MM, including changes in their clinical manifestations, biochemical, CT and EMG parameters. The diagnosis was verified by whole exome sequencing of the DYSF gene to identify a homozygous missense mutations (c. 5302C>T) leading to replacement in the polypeptide chain of DYSF p.Arg1768Trp. The differential diagnosis of MM with clinically similar hereditary neuromuscular diseases is discussed. 

Miyoshi myopathyfamilial casedysferlinopathylimb-girdle muscular dystrophiesDYSG genewhole genome sequencingelectromyographyhypercreatine phosphatemia neural amyotrophymyopathymissense mutationмиопатия Миошисемейное наблюдениедисферлинопатияпоясно-конечностные мышечные дистрофииген DYSFполногеномное секвенированиеэлектромиографиягиперкреатинфосфатемияневральная амиотрофиямиопатиямиссенс-мутация1. Urtizberea J.А. Дисферлинопатии: проблема за пределами дистальных миопатий. Нервно-мышечные болезни 2012;(2):20–8. [Andoni Urtizberea J. Dysferlinopathy: a problem beyond the scope of distal myopathies. Nervno-myshechnye bolezni = Neuromuscular Diseases 2012;(2):20–8. (In Russ.)].Urtizberea J.А. Дисферлинопатии: проблема за пределами дистальных миопатий. Нервно-мышечные болезни 2012;(2):20–8. [Andoni Urtizberea J. Dysferlinopathy: a problem beyond the scope of distal myopathies. Nervno-myshechnye bolezni = Neuromuscular Diseases 2012;(2):20–8. (In Russ.)].2. Bushby K.M. The limb-girdle muscular dystrophies-multiple genes, multiple mechanisms. Hum Mol Genet 1999;8(10):1875–82.Bushby K.M. The limb-girdle muscular dystrophies-multiple genes, multiple mechanisms. Hum Mol Genet 1999;8(10):1875–82.3. Bushby K.M. Making sense of the limbgirdle muscular dystrophies. Brain 1999;122:1403–20.Bushby K.M. Making sense of the limbgirdle muscular dystrophies. Brain 1999;122:1403–20.4. Nigro V., Savarese M. Genetic basis of limb-girdle muscular dystrophies: the 2014 update. Acta Myol 2014;33(1):1–12.Nigro V., Savarese M. Genetic basis of limb-girdle muscular dystrophies: the 2014 update. Acta Myol 2014;33(1):1–12.5. Miyoshi K., Kawai H., Iwasa M. et al. Autosomal recessive distal muscular dystrophy as a new type of progressive muscular dystrophy: seventeen cases in eight families including an autopsied case. Brain 1986;109:31–54.Miyoshi K., Kawai H., Iwasa M. et al. Autosomal recessive distal muscular dystrophy as a new type of progressive muscular dystrophy: seventeen cases in eight families including an autopsied case. Brain 1986;109:31–54.6. Illa I., Serrano-Munuera C., Gallardo E. et al. Distal anterior compartment myopathy: a dysferlin mutation causing a new muscular dystrophy phenotype. Ann Neurol 2001;49(1):130–4.Illa I., Serrano-Munuera C., Gallardo E. et al. Distal anterior compartment myopathy: a dysferlin mutation causing a new muscular dystrophy phenotype. Ann Neurol 2001;49(1):130–4.7. Weiler T., Bashir R., Anderson L. et al. Identical mutation in patients with limb girdle muscular dystrophy type 2B or Miyoshi myopathy suggests a role for modifier gene(s). Hum Mol Genet 1999;8(5):871–7.Weiler T., Bashir R., Anderson L. et al. Identical mutation in patients with limb girdle muscular dystrophy type 2B or Miyoshi myopathy suggests a role for modifier gene(s). Hum Mol Genet 1999;8(5):871–7.8. Bashir R., Keers S., Strachan T. et al. Genetic and physical mapping at the limbgirdle muscular dystrophy locus (LGMD2B) on chromosome 2p. Genomics 1996;33(1):46–52.Bashir R., Keers S., Strachan T. et al. Genetic and physical mapping at the limbgirdle muscular dystrophy locus (LGMD2B) on chromosome 2p. Genomics 1996;33(1):46–52.9. Illarioshkin S.N., Ivanova-Smolenskaya I.A., Tanaka H. et al. Clinical and molecular analysis of a large family with three distinct phenotypes of progressive muscular dystrophy. Brain 1996;119:1895–909.Illarioshkin S.N., Ivanova-Smolenskaya I.A., Tanaka H. et al. Clinical and molecular analysis of a large family with three distinct phenotypes of progressive muscular dystrophy. Brain 1996;119:1895–909.10. Bashir R., Britton S., Strachan T. et al. A gene related to Caenorhabditis elegans spermatogenesis factor fer-1 is mutated in limb-girdle muscular dystrophy type 2B. Nat Genet 1998;20(1):37–42.Bashir R., Britton S., Strachan T. et al. A gene related to Caenorhabditis elegans spermatogenesis factor fer-1 is mutated in limb-girdle muscular dystrophy type 2B. Nat Genet 1998;20(1):37–42.11. Illarioshkin S.N., IvanovaSmolenskaya I.A., Greenberg C.R. et al. Identical dysferlin mutation in limb-girdle muscular dystrophy type 2B and distal myopathy. Neurology 2000;55(12):1931–3.Illarioshkin S.N., IvanovaSmolenskaya I.A., Greenberg C.R. et al. Identical dysferlin mutation in limb-girdle muscular dystrophy type 2B and distal myopathy. Neurology 2000;55(12):1931–3.12. Takahashi T., Aoki M., Suzuki N. et al. Clinical features and a mutation with late onset of limb girdle muscular dystrophy 2B. J Neurol Neurosurg Psychiatry 2013;84(4):433–40.Takahashi T., Aoki M., Suzuki N. et al. Clinical features and a mutation with late onset of limb girdle muscular dystrophy 2B. J Neurol Neurosurg Psychiatry 2013;84(4):433–40.13. Nguyen K., Bassez G., Krahn M. et al. Phenotypic study in 40 patients with dysferlin gene mutations: high frequency of atypical phenotypes. Arch Neurol 2007;64(8):1176–82.Nguyen K., Bassez G., Krahn M. et al. Phenotypic study in 40 patients with dysferlin gene mutations: high frequency of atypical phenotypes. Arch Neurol 2007;64(8):1176–82.14. Urtizberea J.A., Bassez G., Leturcq F. et al. Dysferlinopathies. Neurol India 2008;56(3):289–97.Urtizberea J.A., Bassez G., Leturcq F. et al. Dysferlinopathies. Neurol India 2008;56(3):289–97.15. Никитин С.С. Электромиографические стадии денервационно-реиннервационного процесса при нервномышечных болезнях: необходимость ревизии. Нервно-мышечные болезни 2015;5(2):16–24. [Nikitin S.S. Electromyographic stages of the denervation – renervation process at neuro-muscular diseases: need to be revised. Nervno-myshechnye bolezni = Neuromuscular Diseases 2015;5(2):16–24. (In Russ.)].Никитин С.С. Электромиографические стадии денервационно-реиннервационного процесса при нервномышечных болезнях: необходимость ревизии. Нервно-мышечные болезни 2015;5(2):16–24. [Nikitin S.S. Electromyographic stages of the denervation – renervation process at neuro-muscular diseases: need to be revised. Nervno-myshechnye bolezni = Neuromuscular Diseases 2015;5(2):16–24. (In Russ.)].