Skeletal Muscle Laminopathies: A Review of Clinical and Molecular Features

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2016 Aug 17

PMID 27529282

Citations 49

Authors

Lorenzo Maggi

Nicola Carboni

Pia Bernasconi

Affiliations

Soon will be listed here.

Abstract

LMNA-related disorders are caused by mutations in the LMNA gene, which encodes for the nuclear envelope proteins, lamin A and C, via alternative splicing. Laminopathies are associated with a wide range of disease phenotypes, including neuromuscular, cardiac, metabolic disorders and premature aging syndromes. The most frequent diseases associated with mutations in the LMNA gene are characterized by skeletal and cardiac muscle involvement. This review will focus on genetics and clinical features of laminopathies affecting primarily skeletal muscle. Although only symptomatic treatment is available for these patients, many achievements have been made in clarifying the pathogenesis and improving the management of these diseases.

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References

Chatzifrangkeskou M, Bonne G, Muchir A . Nuclear envelope and striated muscle diseases. Curr Opin Cell Biol. 2014; 32:1-6. DOI: 10.1016/j.ceb.2014.09.007. View

Azibani F, Muchir A, Vignier N, Bonne G, Bertrand A . Striated muscle laminopathies. Semin Cell Dev Biol. 2014; 29:107-15. DOI: 10.1016/j.semcdb.2014.01.001. View

Nigro G, Russo V, Rago A, Papa A, Carbone N, Marchel M . Regional and transmural dispersion of repolarisation in patients with Emery-Dreifuss muscular dystrophy. Kardiol Pol. 2012; 70(11):1154-9. View

Roncarati R, Viviani Anselmi C, Krawitz P, Lattanzi G, von Kodolitsch Y, Perrot A . Doubly heterozygous LMNA and TTN mutations revealed by exome sequencing in a severe form of dilated cardiomyopathy. Eur J Hum Genet. 2013; 21(10):1105-11. PMC: 3778353. DOI: 10.1038/ejhg.2013.16. View

Raffaele di Barletta M, Ricci E, Galluzzi G, Tonali P, Mora M, Morandi L . Different mutations in the LMNA gene cause autosomal dominant and autosomal recessive Emery-Dreifuss muscular dystrophy. Am J Hum Genet. 2000; 66(4):1407-12. PMC: 1288205. DOI: 10.1086/302869. View

Choi J, Muchir A, Wu W, Iwata S, Homma S, Morrow J . Temsirolimus activates autophagy and ameliorates cardiomyopathy caused by lamin A/C gene mutation. Sci Transl Med. 2012; 4(144):144ra102. PMC: 3700376. DOI: 10.1126/scitranslmed.3003875. View

Ramos F, Chen S, Garelick M, Dai D, Liao C, Schreiber K . Rapamycin reverses elevated mTORC1 signaling in lamin A/C-deficient mice, rescues cardiac and skeletal muscle function, and extends survival. Sci Transl Med. 2012; 4(144):144ra103. PMC: 3613228. DOI: 10.1126/scitranslmed.3003802. View

Arimura T, Onoue K, Takahashi-Tanaka Y, Ishikawa T, Kuwahara M, Setou M . Nuclear accumulation of androgen receptor in gender difference of dilated cardiomyopathy due to lamin A/C mutations. Cardiovasc Res. 2013; 99(3):382-94. DOI: 10.1093/cvr/cvt106. View

Barton R, Worman H . Prenylated prelamin A interacts with Narf, a novel nuclear protein. J Biol Chem. 1999; 274(42):30008-18. DOI: 10.1074/jbc.274.42.30008. View

10.

Worman H . Nuclear lamins and laminopathies. J Pathol. 2011; 226(2):316-25. PMC: 6673656. DOI: 10.1002/path.2999. View

11.

Boudreau E, Labib S, Bertrand A, Decostre V, Bolongo P, Sylvius N . Lamin A/C mutants disturb sumo1 localization and sumoylation in vitro and in vivo. PLoS One. 2012; 7(9):e45918. PMC: 3448699. DOI: 10.1371/journal.pone.0045918. View

12.

Cesarini E, Mozzetta C, Marullo F, Gregoretti F, Gargiulo A, Columbaro M . Lamin A/C sustains PcG protein architecture, maintaining transcriptional repression at target genes. J Cell Biol. 2015; 211(3):533-51. PMC: 4639869. DOI: 10.1083/jcb.201504035. View

13.

Webster B, Lusk C . Border Safety: Quality Control at the Nuclear Envelope. Trends Cell Biol. 2015; 26(1):29-39. PMC: 4698192. DOI: 10.1016/j.tcb.2015.08.002. View

14.

van Engelen B, Muchir A, Hutchison C, van der Kooi A, Bonne G, Lammens M . The lethal phenotype of a homozygous nonsense mutation in the lamin A/C gene. Neurology. 2005; 64(2):374-6. DOI: 10.1212/01.WNL.0000149763.15180.00. View

15.

Pasotti M, Klersy C, Pilotto A, Marziliano N, Rapezzi C, Serio A . Long-term outcome and risk stratification in dilated cardiolaminopathies. J Am Coll Cardiol. 2008; 52(15):1250-60. DOI: 10.1016/j.jacc.2008.06.044. View

16.

Zastrow M, Vlcek S, Wilson K . Proteins that bind A-type lamins: integrating isolated clues. J Cell Sci. 2004; 117(Pt 7):979-87. DOI: 10.1242/jcs.01102. View

17.

Muchir A, Kim Y, Reilly S, Wu W, Choi J, Worman H . Inhibition of extracellular signal-regulated kinase 1/2 signaling has beneficial effects on skeletal muscle in a mouse model of Emery-Dreifuss muscular dystrophy caused by lamin A/C gene mutation. Skelet Muscle. 2013; 3(1):17. PMC: 3702458. DOI: 10.1186/2044-5040-3-17. View

18.

Goizet C, Ben Yaou R, Demay L, Richard P, Bouillot S, Rouanet M . A new mutation of the lamin A/C gene leading to autosomal dominant axonal neuropathy, muscular dystrophy, cardiac disease, and leuconychia. J Med Genet. 2004; 41(3):e29. PMC: 1735710. DOI: 10.1136/jmg.2003.013383. View

19.

Scaffidi P, Misteli T . Reversal of the cellular phenotype in the premature aging disease Hutchinson-Gilford progeria syndrome. Nat Med. 2005; 11(4):440-5. PMC: 1351119. DOI: 10.1038/nm1204. View

20.

Dechat T, Adam S, Taimen P, Shimi T, Goldman R . Nuclear lamins. Cold Spring Harb Perspect Biol. 2010; 2(11):a000547. PMC: 2964183. DOI: 10.1101/cshperspect.a000547. View