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The multidisciplinary and multisystemic issue of laminopathies: many diseases, one gene

Vaykhanskaya T. G.1, Sivitskaya L. N.2, Danilenko N. G.2, Kurushko T. V.1, Davydenko O. G.2
1 – State Institution Republican Science and Practice Center “Cardiology”, R. Luxemburg 110, Minsk 220036, Republic of Belarus
2 – State Science Institution, “Institute of Genetics and Cytology of Belarus National
Academy of Sciences”, Akademicheskaya 27, Minsk 220072, Republic of Belarus

Keywords: laminopathies, lamin protein function, lamin a/c gene (lmna), dilated cardiomyopathy, Emery-Dreifuss muscular dystrophy, limb-girdle muscular dystrophy type IB, heart rhythm disturbances, conduction disorder, cardioverter-defibrillator

DOI: 10.18087/rhfj.2016.3.2223

Studies of the recent decade have significantly expanded the array of monogenic diseases associated with mutations in the la­min A/C gene (LMNA) which encodes a group of proteins performing important functions in the cell nucleus. This abnormality is characteri­zed by multiple systemic and tissue injuries, including cardiac phenotypes (dilated cardiomyopathy with or without muscular dystrophy), muscular dystrophies (Emery-Dreifuss, congenital, and limb-girdle muscular dystrophies), lipodystrophy (familial partial lipodystrophy, Kobberling and Dunnigan types), neuropathies (spinal and Charkot-Marie-Tooth type 2 neuropathies), progeroid phenotypes (mandibuloacral dysplasia, Hutchinson-Gilford progeria, atypical Werner syndrome), etc. The article presents an up-to-date review of literature and highlights major issues of laminopathies: epidemiology of muscular and cardiac phenotypes; lipodystrophy and progeria syndromes; structure and function of the lamin protein and the LMNA gene; pathophysio­logical and molecular biological mechanisms of the laminopathy pathogenesis; clinical manifestations, diagnostics and treatment of laminopathy cardiac phenotypes exampled by three case reports (dilated cardiomyopathy /DCMP/ type 1A with conduction defects; DCMP in combination with Emery-Dreifuss muscular dystrophy, and DCMP with limb-girdle muscular dystrophy type 1B). LMNA gene mutations are found in 6–10 % of patients with different DCMP types and in 30–33 % of patients with conduction defects. The lamin phenotype of cardiomyopathy is characterized by rapid progression of HF, early life-threatening arrhythmias, and a very high risk of sudden death, which justifies the need for preventive implantation of a pacemaker or a cardioverter-defibrillator.
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Vaykhanskaya T. G., Sivitskaya L. N., Danilenko N. G., Kurushko T. V., Davydenko O. G. The multidisciplinary and multisystemic issue of laminopathies: many diseases, one gene. Russian Heart Failure Journal. 2016;17 (3):201–211

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