A Heterozygous ZMPSTE24 Mutation Associated with Severe Metabolic Syndrome, Ectopic Fat Accumulation, and Dilated Cardiomyopathy.

摘要: ZMPSTE24 encodes the only metalloprotease, which transforms prelamin into mature lamin A. Up to now, mutations in have been linked Restrictive Dermopathy (RD), Progeria or Mandibulo-Acral Dysplasia (MAD). We report here phenotype of a patient referred for severe metabolic syndrome and cardiomyopathy, carrying mutation ZMPSTE24. The presented with partial lipodystrophic associating hypertriglyceridemia, early onset type 2 diabetes, android obesity truncal abdominal fat accumulation but without subcutaneous lipoatrophy. Other clinical features included acanthosis nigricans, liver steatosis, dilated high myocardial hepatic triglycerides content. Mutated fibroblasts from showed increased nuclear shape abnormalities premature senescence as demonstrated by decreased Population Doubling Level, an beta-galactosidase activity BrdU incorporation rate. Reduced A expression siRNA targeted toward LMNA transcripts resulted anomalies. show that central lipoatrophy is associated laminopathy due heterozygous missense Given prevalence general population, absence familial study, causative link between cannot be formally established. Nevertheless, altered lamina architecture observed mutated are responsible cellular could contribute this patient.