title: [Laminopathies: one gene, several diseases].
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: UPMC Université Paris VI, IFR14, 75013 Paris, France. a.bertrand@institut-myologie.org
authors: Anne T
authors: AT
authors: Bertrand
authors: Khadija
authors: K
authors: Chikhaoui
authors: Rabah
authors: R
authors: Ben Yaou
authors: Gisèle
authors: G
authors: Bonne
mesh_terms: D019588:Aging, Premature / Q000145:classification / Q000235:genetics* / Q000503:physiopathology; D000818:Animals; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000503:physiopathology; D004195:Disease Models, Animal; D018740:Genetic Heterogeneity; D005838:Genotype; D006801:Humans; D034904:Lamin Type A / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D008060:Lipodystrophy / Q000235:genetics* / Q000503:physiopathology; D008336:Mandibular Diseases / Q000235:genetics / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009136:Muscular Dystrophies / Q000145:classification / Q000235:genetics* / Q000503:physiopathology; D009137:Muscular Dystrophy, Animal / Q000235:genetics; D009154:Mutation; D010641:Phenotype; D013045:Species Specificity; D013329:Structure-Activity Relationship
chemical_list: C494847:LMNA protein, human; D034904:Lamin Type A