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[Laminopathies: one gene, several diseases].
Biol Aujourdhui. 2011; 205(3):147-62.BA

Abstract

Lamins A and C, encoded by the LMNA gene, are nuclear proteins expressed in all post-mitotic cells. Together with B-type lamins, they form a meshwork of proteins beneath the inner nuclear membrane, the lamina, in connection with the cytoskeleton. Lamins A/C also interact with chromatin and numerous proteins, including transcription factors. Mutations in LMNA are responsible for more than ten different disorders, commonly called "laminopathies". These diseases affect tissues in a specific (striated muscle, adipose tissue, peripheral nerve) or in a systemic manner (premature ageing syndromes). This wide spectrum of phenotypes is associated to a wide variety of mutations. This large clinical and genetic heterogeneity, unique to the LMNA gene, makes genotype-phenotype relations particularly difficult to establish. However, correlations have been obtained in several cases. Hence, LMNA mutations identified in premature ageing syndromes lead to the accumulation of immature proteins with a toxic effect for cells. Mutations in laminopathies of the adipose tissue mainly localize in the Ig-like domain of the proteins, potentially affecting the interaction with the SREBP-1 transcription factor. In laminopathies of the striated muscles, the mutations are spread throughout the gene. These mutations are thought to induce structural modifications of the proteins, thereby affecting their polymerization into nuclear lamina. Such defect would lead to a mechanical weakness of the nuclear lamina and of the cells, particularly in striated muscles continuously stretching. The exploration of pathophysiological mechanisms of LMNA mutations largely benefits from the numerous mouse models created, which have been widely used to analyze affected molecular pathways and to test putative therapeutic treatments.

Authors+Show Affiliations

UPMC Université Paris VI, IFR14, 75013 Paris, France. a.bertrand@institut-myologie.orgNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

English Abstract
Journal Article
Review

Language

fre

PubMed ID

21982404

Citation

Bertrand, Anne T., et al. "[Laminopathies: One Gene, Several Diseases]." Biologie Aujourd'hui, vol. 205, no. 3, 2011, pp. 147-62.
Bertrand AT, Chikhaoui K, Ben Yaou R, et al. [Laminopathies: one gene, several diseases]. Biol Aujourdhui. 2011;205(3):147-62.
Bertrand, A. T., Chikhaoui, K., Ben Yaou, R., & Bonne, G. (2011). [Laminopathies: one gene, several diseases]. Biologie Aujourd'hui, 205(3), 147-62. https://doi.org/10.1051/jbio/2011017
Bertrand AT, et al. [Laminopathies: One Gene, Several Diseases]. Biol Aujourdhui. 2011;205(3):147-62. PubMed PMID: 21982404.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - [Laminopathies: one gene, several diseases]. AU - Bertrand,Anne T, AU - Chikhaoui,Khadija, AU - Ben Yaou,Rabah, AU - Bonne,Gisèle, Y1 - 2011/10/11/ PY - 2011/04/01/received PY - 2011/10/11/entrez PY - 2011/10/11/pubmed PY - 2012/1/4/medline SP - 147 EP - 62 JF - Biologie aujourd'hui JO - Biol Aujourdhui VL - 205 IS - 3 N2 - Lamins A and C, encoded by the LMNA gene, are nuclear proteins expressed in all post-mitotic cells. Together with B-type lamins, they form a meshwork of proteins beneath the inner nuclear membrane, the lamina, in connection with the cytoskeleton. Lamins A/C also interact with chromatin and numerous proteins, including transcription factors. Mutations in LMNA are responsible for more than ten different disorders, commonly called "laminopathies". These diseases affect tissues in a specific (striated muscle, adipose tissue, peripheral nerve) or in a systemic manner (premature ageing syndromes). This wide spectrum of phenotypes is associated to a wide variety of mutations. This large clinical and genetic heterogeneity, unique to the LMNA gene, makes genotype-phenotype relations particularly difficult to establish. However, correlations have been obtained in several cases. Hence, LMNA mutations identified in premature ageing syndromes lead to the accumulation of immature proteins with a toxic effect for cells. Mutations in laminopathies of the adipose tissue mainly localize in the Ig-like domain of the proteins, potentially affecting the interaction with the SREBP-1 transcription factor. In laminopathies of the striated muscles, the mutations are spread throughout the gene. These mutations are thought to induce structural modifications of the proteins, thereby affecting their polymerization into nuclear lamina. Such defect would lead to a mechanical weakness of the nuclear lamina and of the cells, particularly in striated muscles continuously stretching. The exploration of pathophysiological mechanisms of LMNA mutations largely benefits from the numerous mouse models created, which have been widely used to analyze affected molecular pathways and to test putative therapeutic treatments. SN - 2105-0678 UR - https://www.unboundmedicine.com/medline/citation/21982404/[Laminopathies:_one_gene_several_diseases]_ L2 - https://medlineplus.gov/musculardystrophy.html DB - PRIME DP - Unbound Medicine ER -