Résumé :
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Laminopathies are a heterogeneous group of human disorders linked to mutations in the LMNA gene encoding A type lamins or in genes encoding lamin A-associated proteins. Numerous mutations of the LMNA gene cause overlapping clinical phenotypes, such as the S143F lamin A/C mutation which causes a progeroid syndrome with muscle involvement. Here we report a comparative study of two different cell lines, one bearing the S143F LMNA mutation, the other affected by double R298C/R298C LMNA and delK37 emerin mutation, obtained from patients affected by muscle wasting and systemic involvement. The first patient was affected by Werner syndrome with muscle involvement, the second patient was affected by a severe form of Charcot-Marie Tooth neuropathy (CMT2). Our results show that nuclear defects consisting of impressive invaginations of the nuclear envelope and accumulation of unprocessed prelamin A characterize both cell lines. Prelamin A accumulation had not been detected previously in laminopathies with muscle involvement and could explain the nuclear envelope disorganization as well as the severity of the clinical phenotype.
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