[Laminopathies: lipodystrophies, insulin resistance, syndromes of accelerated ageing... and others].
Laminopathies are a group of diseases due to mutations of type A-lamins, a group of proteins lining the inner aspect of cell nuclei. These diseases illustrate the complexity of the genotype-phenotype relationship characteristic of same genetic diseases. Since the discovery of the causal role of LMNA gene mutations in the genesis of Emery Dreifuss muscular dystrophy in 1999, no less than eight other diseases have been associated with mutations of this same gene! The tissue-specific nature of the clinical manifestations, contrasting with the ubiquitous expression of these proteins, has incited much research concerning the physiological role of lamins, considered to be much broader than the structural function initially put forward. Certain laminopathies, which combine insulin resistance, android distribution of adipose tissue, dyslipidemia, early atherosclerosis, and hepatic steatosis, appear very similar though more severe to the frequent dysmetabolism syndrome. The relationships of laminopathies with accelerated aging syndrome, Hutchinson-Gilford progeria, or progeroid syndromes, which are also related to A/C lamin anomalies, could provide new avenues of research on the pathogenesis of the metabolic syndrome. In addition, clinicians have to be aware of atypical and milder forms of laminopathies, that require specific investigations and molecular screening of relatives allowing an adequate medical management.
Vigouroux
C
C
Faculté de médecine Saint-Antoine, Université Pierre et Marie Curie, INSERM U680, 27, rue Chaligny, 75 571 Paris Cedex 12. vigouroux@st-antoine.inserm.fr
D019588:Aging, Premature / Q000235:genetics*; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D034882:Lamins / Q000235:genetics*; D008060:Lipodystrophy / Q000235:genetics*; D020389:Muscular Dystrophy, Emery-Dreifuss / Q000235:genetics; D009154:Mutation
D034882:Lamins