Annals of Clinical and Experimental NeurologyAnnals of Clinical and Experimental NeurologyАнналы клинической и экспериментальной неврологии2075-54732409-2533Eco-Vector38910.17816/psaic389ReviewsОбзорыUnknownClinical and genetic characteristics of hereditary laminopathiesКлинико-генетическая характеристика наследственных ламинопатийhttps://orcid.org/0000-0001-5602-2805DadalyElena L.ДадалиЕлена Леонидовна
Russian Federation

D. Sci. (Med.), Prof., Head, Scientific advisory department

д.м.н., проф., зав. научно-консультативного отд.

platonova@neurology.ruBilevaD. S.БилеваД. С.
Russian Federation
platonova@neurology.ruUgarovI. V.УгаровИ. В.
Russian Federation
platonova@neurology.ruResearch Centre for Medical GeneticsФГБНУ «Медико-генетический научный центр имени академика Н.П. Бочкова»Department of Genetics, Medical-Biologic Faculty, Russian State Medical UniversityКафедра генетики медико-биологического факультета Российского государственного медицинского университетаResearch Center for Medical Genetics, Russian Academy of Medical SciencesФГБНУ «Медико-генетический научный центр имени академика Н.П. Бочкова»1412200824283307022017Copyright ©; 2008, Dadaly E.L., Bileva D.S., Ugarov I.V.Copyright ©; 2008, Dadaly E.L., Bileva D.S., Ugarov I.V.2008Dadaly E.L., Bileva D.S., Ugarov I.V.Dadaly E.L., Bileva D.S., Ugarov I.V.https://creativecommons.org/licenses/by/4.0https://annaly-nevrologii.com/pathID/article/view/389

Naminopathies belong to a wide allelic series of diseases caused by mutations of one gene, LMNA, encoding for protein lamin A/C. Different mutations in the LMNA gene cause autosomal dominant and autosomal recessive Emery–Dreifuss muscular dystrophy, dilated cardiomyopathy 1A, familial partial lipodystrophy, atypical Werner’s syndrome, Hutchinson–Gilford progeria and motor-sensory neuropathy type 2B1. In the review, the lamin structure and functions, clinical characteristics of hereditary laminopathies, their etiology, pathogenesis and molecular bases are discussed.

Ламинопатии относятся к обширной аллельной серии болезней, вызванных мутациями одного гена – LMNA, кодирующего белок ламин А/С. Различные мутации в гене LMNA вызывают аутосомно-доминантную и аутосомно-рецессивную мышечную дистрофию Эмери–Дрейфуса, дилятационную кардиомиопатию 1A, семейную частичную липодистрофию, атипичный синдром Вернера, прогерию Хатчинсона–Гилфорда и моторно-сенсорную полинейропатию типа 2B1. В обзоре рассматриваются структура и функции ламинов, клиническая характеристика наследственных ламинопатий, их этиопатогенез и молекулярные основы развития.

laminslaminopathiesetiologypathogenesisclinical-genetic characteristicsламиныламинопатииэтиологияпатогенезклинико-генетические характеристикиБилева Д.С., Дадали Е.Л., Барышникова Н.В. и др. О классифиикации наследственных моногенных заболеваний на примере спинальной мышечной атрофии. Вестник РГМУ 2006; 3: 59–65.Билева Д.С., Ситников В.Ф., Дадали Е.Л. О классификации и нозологии генетически гетерогенной моторноосенсорной невропатии. Вестник РГМУ 2007; 3: 44–49.Иллариошкин С.Н., Иванова–Смоленская И.Ф., Маркова Е.Д. ДНК-диагностика и медикоогенетическое консультирование в неврологии. М.: МИА, 2002.Руденская Г.Е., Тверская С.М., Чухрова А.Л. и др. Разнообразие болезней, обусловленных мутациями в гене LMNA. Мед. генетика 2004; 12: 569–576.Руденская Г.Е., Тверская С.М., Поляков А.В. Прогрессирующая мышечная дистрофия Эмери–Дрейфуса: клинико-генетическое разнообразие и генодиагностика. Мед. генетика 2002; 2: 50–56.Тверская С.М., Чухрова А.Л., Дадали Е.Л. и др. Разнообразие клинических проявлений моногенных наследственных заболеваний, обусловленных мутациями в одном гене. Мед. генетика 2007; 3: 3–10.Aebi U., Cohn J., Buhle E.L. et al. The nuclear lamina is a meshwork of intermediateetype filaments. Nature 1986; 323: 560 –564.Barletta M.R.D., Galluzzi G.R.E. et al. Different mutations in the LMNA gene cause autoosomal dominant and autosomal recessive Emery–Dreifuss muscular dystrophy. Am. J. Hum. Genet. 2000; 66:1407–1412.Caux F., Dubosclard E., Lascols O. et al. A new clinical condition linked to a novel mutaation in lamins A and C with generalized lipoatrophy, insulinnresistant diabetes, disseminated leuukomelanodermic papules, liver steatosis, and cardiomyopathy. J. Clin. Endocr. Metab. 2003; 88: 1006–1013.Chen L., Lee L., Kudlow B.A. et al. LMNA mutations in atypical Werner’s syndrome. Lancet 2003; 362: 440–445.Cogulu O., Gunduz C., Darcan S. et al. Mandibuloacral dysplasia with absent breast development. Am. J. Med. Genet. 2003; 119A: 391–392.Dorner D., Gotzmann J., Foisner R. Nucleoplasmic lamins and their interaction partners, LAP2alpha, Rb, and BAF, in transcriptional regulation. FEBS J. 2007; 274: 1362–1373.Emery A.E., Dreifuss F.E. Unusual type of benign XXlinked muscular dystrophy. J. Neurol. Neurosurg. Psychiatry 1966; 29: 338–342.Fatkin D., MacRae C., Sasaki T. et al. Missense mutations in the rodomain of the lamin A/C gene as causes of dilated cardiomyopathy and conduction system disease. N. Engl. J. Med. 1999; 341: 1715–1724.Favreau C., Higuet D., Courvalin J. et al. Expresion of a mutant Lamin A that causes Emery–Dreifuss muscular dystrophy inhibitis in vitro differentiation of C2C12 myoblasts. Mol. Cel. Biol. 2004; 24: 1481–1492.Fisher D., Chaudhary N., Blobel G. et al. cDNA sequencing of nuclear lamins A and C reveals primary and secondary structure homology to intermediate filament proteins. Proc. Natl. Acad. Sci. USA.1986; 83: 6450–6454.Fokkema I.F., Dunnen J.T., Taschner P.E. LOVD: Easy creation of a locussspecific sequence variation database using an «LSDBBinnaabox» approach. Hum. Mutat. 2005; 26: 63–68.Fong L.G., Ji J.Y., Reue K. et al. Lamins A and C but not lamin B1 gegulate nuclear mechanics. J. Biol. Chem. 2006; 281: 25768–25780.Gilford H. Ateleiosis and progeria: continuous youth and premature old age. Brit. Med. J. 1904; 2: 914–918.Goldman R.D., Gruenbaum Y., Moir R.D. et al. Nuclear lamins: building blocks of nuclear architecture. Genes & Development 2002; 16: 533–547.Hennekam R.C.M. Hutchinson–Gilford progeria syndrome: review of the phenotype. Am. J. Med. Genet. 2006; 140A: 2603–2624.Holaska J.M., Lee K.K., Kowalski A.K. et al. Transcriptional repressor germ cellless (GCL) and barrier to autointegration factor (BAF) compete for binding to emerin in vitro. J. Biol. Chem. 2003; 278:6969–6975.Hutchinson J. Case of congenital absence of hair, with atrophic condition of the skin and its appendages, in a boy whose mother had been almost wholly bald from alopecia areata from the age of six. Lancet 1886; I: 923.Hutchison C.J & Worman H.J. AAtype lamins: guardians of the soma? Nat. Cell Biol. 2004; 6: 1062–1067.Kitaguchi T., Matsubara S., Sato M. et al. A missense mutation in the exon 8 of lamin A/C gene in a Japanese case of autosomal dominant limbbgirdle muscular dystrophy and cardiac conduction block. Neuromuscul. Disord. 2001; 11: 542–546.Lammerding J., Schulze P.C., Takahashi T. et al. Lamin A/C deficiency causes defective nuclear mechanics and mechanotransduction. J. Clin. Invest. 2004; 113: 370–378.Leiden Muscular Dystrophy page. http://www.dmd.nl/nmdb/index.php?select_db=LMNA.Lin F., Worman H.J. Stuctural organization of the human genencoding nuclear Lamin A and nuclear Lamin C. J. Biol. Chem. 1993; 268: 16321–16326.Maidment S.L., Ellis J.A. Muscular dystrophies, dilated cardiomyopathy, lipodystrophy and neuropathy: the nuclear connection. Exp. Rev. Mol. Med. 2002; http:// www.expertreviews.org/02004842h.htm.Margalit A.Y., Gruenbaum Y., Goldman R.D. et al. The nuclear lamina comes of age. Nat. Rev. Mol. Cell Biol. 2005; 6: 21–31.Miller R.G., Layzer R.B., Mellenthin M.A. et al. Emery–Dreifuss muscular dystrophy with autosomal dominant transmission. Neurology 1985; 35: 1230–1233.Muchir A., Bonne G., van der Kooi A.J. et al. Identification of mutations in the gene encoding lamins A/C in autosomal dominant limb girdle muscular dystrophy with atrioventricular conduc tion disturbances (LGMD1B). Hum. Mol. Genet. 2000; 9: 1453–1459.Navarro C.L., De SandreeGiovannoli A., Bernard R. et al. Lamin A and ZMPSTE24 (FACEE1) defects cause nuclear disorganization and identity restrictive dermopathy as a lethal neonatal laminopathy. Hum. Mol. Genet. 2004; 13: 2493–2503.Parry D.A., Conway J.F., Steinert P.M. Structural studies on lamin. Similarities and differences between lamin and intermediate filament proteins. Biochem. J. 1986; 238: 305–308.Raharjo W.H., Enarson P., Sullivan T. et al. Nuclear envelope defects associated with LMNA mutations cause dilated cardiomyopathy and Emery–Dreifuss muscular dystrophy. J. Cell Sci. 2001; 114: 4447–4457.Skalli O., Chou Y.H., Goldman R.D. Cell cycleedependent changes in the organization of an intermediate filamenttassociated protein: correlation with phosphorylation by p34cdc2. Proc. Natl. Acad. Sci. USA 1992; 89: 11959–11963.Somech R., Shaklai S., Amariglio N. et al. Nuclear envelopathies – raising the nuclear veil. Pediat. Res. 2005; 57: 8–15.Spann T., Moir R.D., Goldman A.E. et al. Disruption of nuclear lamin organization alters the distribution of replication factors and inhibits DNA synthesis. J. Cell Biol. 1997; 136: 1201–1212.Spann T.P., Goldman A.E., Wang C. et al. Alteration of nuclear lamin organization inhibits RNA polymerase IIIdependent transcription. J. Cell Biol. 2002; 156: 603–608.Tasir M., Azzedine H., Assami S. et al. Phenotypic variability in autosomal recessive axonal Charcot–Marie–Tooth disease due to the R298C mutation in lamin A/C. Brain 2004; 127: 154–163.Tzur Y.B., Wilson K.L., Gruenbaum Y. SUNNdomain proteins: ‘Velcro’ that links the nucleoskeleton to the cytoskeleton. Nat. Rev. Mol. Cell Biol. 2006; 7: 782–788.Warren D.T., Zhang Q., Weissberg P.L. et al. Nesprins: intracellular scaffolds that maintain cell architecture and coordinate cell function? Expert Rev. Mol. Med. 2005; 7: 1–15Wilkie G.S., Schirmer E.C. Guilt by association. The nuclear envelope proteome and disease. Mol. Cell. Proteomics 2006; 5: 1865–1875.Young S.G., Meta M., Yang S.H. et al. Prelamin A farnesylation and progeroid syndromes. J. Biol. Chem. 2006; 281: 39741–39745.Zastrow M.S., Vlcek S., Wilson R.L. Proteins that bind AAtype lamins: integrating isolated clues. J. Cell Sci. 2004; 117: 979–987.