标题：Normal and aberrant splicing of LMNA
作者：Luo, Yue-Bei; Mastaglia, Frank L.; Wilton, Steve D.
作者机构：[Luo, Yue-Bei; Mastaglia, Frank L.; Wilton, Steve D.] Univ Western Australia, Australian Neuromuscular Res Inst, Ctr Neuromuscular & Neurol Disorders, 更多
通讯作者地址：[Wilton, SD]Murdoch Univ, Ctr Comparat Genom, 90 South St, Murdoch, WA 6150, Australia.
来源：JOURNAL OF MEDICAL GENETICS
关键词：Muscle Disease; Molecular Genetics; Neuromuscular Disease; Developmental
摘要：The LMNA gene gives rise to at least three isoforms (lamin A, C, lamin A Delta 10) 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.