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Normal and aberrant splicing of LMNA
  1. Yue-Bei Luo1,2,
  2. Frank L Mastaglia1,3,
  3. Steve D Wilton1,4
  1. 1Centre for Neuromuscular and Neurological Disorders, Australian Neuro-Muscular Research Institute, University of Western Australia, Perth, Australia
  2. 2Laboratory of Neuromuscular Disorders, Department of Neurology, Qilu Hospital, Shandong University, Jinan, China
  3. 3Institute for Immunology & Infectious Diseases, Murdoch University, Perth, Australia
  4. 4Centre for Comparative Genomics, Murdoch University, Perth, Australia
  1. Correspondence to Professor Steve D Wilton, Centre for Comparative Genomics, Murdoch University, 90 South Street, Murdoch, Western Australia 6150, Australia; swilton{at}


The LMNA gene gives rise to at least three isoforms (lamin A, C, lamin AΔ10) as a result of normal alternative splicing, regulated by cis- and trans-acting regulatory factors, as well as the 5′ and 3′ untranslated regions of the gene. The two main isoforms, lamin A and C, are constitutive components of the fibrous nuclear lamina and have diverse physiological roles, ranging from mechanical nuclear membrane maintenance to gene regulation. The clinical spectrum of diseases (called ‘laminopathies’) caused by LMNA mutations is broad, including at least eight well-characterised phenotypes, some of which are confined to the skeletal muscles or skin, while others are multisystemic. This review discusses the different alternatively spliced isoforms of LMNA and the regulation of LMNA splicing, as well as the subgroup of mutations that affect splicing of LMNA pre-mRNA, and also seeks to bridge the mis-splicing of LMNA at transcript level and the resulting clinical phenotypes. Finally, we discuss the manipulation of LMNA splicing by splice-switching antisense oligonucleotides and its therapeutic potential for the treatment of some laminopathies.

  • Molecular Genetics
  • Muscle Disease
  • Developmental
  • Neuromuscular Disease

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