کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5947861 | 1172374 | 2013 | 5 صفحه PDF | دانلود رایگان |
- We report a novel lamin A/C (LMNA) mutation, c.667GÂ >Â A.
- Symptoms are atherosclerosis, insulin resistance, dyslipidemia and hepatic steatosis.
- The mutation co-segregates with the disease.
- Only fibroblasts from mutation carriers show nuclear blebbing.
- We conclude that a highly likely new pathogenic LMNA mutation might be responsible for premature atherosclerosis.
ObjectiveWe report a novel lamin A/C (LMNA) mutation, p.Glu223Lys, in a family with extensive atherosclerosis, diabetes mellitus and steatosis hepatis.MethodsSequence analysis of LMNA (using Alamut version 2.2), co-segregation analysis, electron microscopy, extensive phenotypic evaluation of the mutation carriers and literature comparison were used to determine the loss of function of this mutation.ResultsThe father of three siblings died at the age of 45 years. The three siblings and the brother and sister of the father were referred to the cardiovascular genetics department, because of the premature atherosclerosis and dysmorphic characteristics observed in the father at autopsy. The novel LMNA mutation, p.Glu223Lys, was identified in the proband and his two sons. Clinical evaluation revealed atherosclerosis, insulin resistance and hypertension in the proband and dyslipidemia and hepatic steatosis in all the patients with the mutation.ConclusionBased on the facts that in silico analysis predicts a possibly pathogenic mutation, the mutation co-segregates with the disease, only fibroblasts from mutation carriers show nuclear blebbing and a similar phenotype was reported to be due to missense mutations in LMNA we conclude that we deal with a pathogenic mutation. We conclude that the phenotype is similar to Dunnigan-type familial partial lipodystrophy.
Journal: Atherosclerosis - Volume 229, Issue 1, July 2013, Pages 169-173