BMB Reports 2018; 51(7): 327-337  https://doi.org/10.5483/BMBRep.2018.51.7.113
Laminopathies; Mutations on single gene and various human genetic diseases
So-mi Kang, Min-Ho Yoon & Bum-Joon Park*
Department of Molecular Biology, College of Natural Science, Pusan National University, Busan 46241, Korea
Correspondence to: Tel: +82-51-510-2220; Fax: +82-51-513-9258; E-mail: bjpark1219@pusan.ac.kr
Received: April 25, 2018; Published online: July 31, 2018.
© Korean Society for Biochemistry and Molecular Biology. All rights reserved.

cc This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Lamin A and its alternative splicing product Lamin C are the key intermediate filaments (IFs) of the inner nuclear membrane intermediate filament. Lamin A/C forms the inner nuclear mesh with Lamin B and works as a frame with a nuclear shape. In addition to supporting the function of nucles, nuclear lamins perform important roles such as holding the nuclear pore complex and chromatin. However, mutations on the Lamin A or Lamin B related proteins induce various types of human genetic disorders and diseases including premature aging syndromes, muscular dystrophy, lipodystrophy and neuropathy. In this review, we briefly overview the relevance of genetic mutations of Lamin A, human disorders and laminopathies. We also discuss a mouse model for genetic diseases. Finally, we describe the current treatment for laminopathies.
Keywords: EDMD, HGPS, Lamin A, Laminopathy, Nuclear membrane
Figures
Fig. 1. Structure of LMNA gene. LMNA, encoding Lamin A/C is composed of 12 exons and the two produced proteins, Lamin A and Lamin C. Exon 1-10 are commonly used for Lamin A and C proteins. However, exon 11 and 12 are only used by Lamin A. Since the end of exon 12 encodes CaaX motif (actually CSIM), only Lamin A is a target for farnesyl-transferase. In addition, the Zmpste24 protease target sequence is located in exon 11. Thus, Farnesylated Lamin A (prelamin A) is processed into mature Lamin A. Lamin C is produced by Exon 1-10 differentially from Lamin A. However, the final exon is differentially used from lamin by alternative splicing (dark blue box in middle panel). Consequently, the six C-terminal amino acids (VSGSRR; dark blue box) are uniquely derived from Lamin A. We also showed the structural domains of Lamin A/C.


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