title: A novel lamin A/C mutation in a Dutch family with premature atherosclerosis.
abstract: OBJECTIVE
  We report a novel lamin A/C (LMNA) mutation, p.Glu223Lys, in a family with extensive atherosclerosis, diabetes mellitus and steatosis hepatis.
  
  
  METHODS
  Sequence 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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  Based 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.
authors: Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105AZ Amsterdam, The Netherlands.
authors: A A W
authors: AA
authors: Weterings
authors: I A W
authors: IA
authors: van Rijsingen
authors: A S
authors: AS
authors: Plomp
authors: A H
authors: AH
authors: Zwinderman
authors: R H
authors: RH
authors: Lekanne Deprez
authors: M M
authors: MM
authors: Mannens
authors: M A
authors: MA
authors: van den Bergh Weerman
authors: A C
authors: AC
authors: van der Wal
authors: S J
authors: SJ
authors: Pinto-Sietsma
mesh_terms: D000328:Adult; D017668:Age of Onset; D050197:Atherosclerosis / Q000235:genetics*; D020405:Dermis / Q000473:pathology; D003920:Diabetes Mellitus / Q000235:genetics; D005192:Family Health; D017809:Fatal Outcome; D005234:Fatty Liver / Q000235:genetics; D005260:Female; D005347:Fibroblasts / Q000473:pathology / Q000648:ultrastructure; D006801:Humans; D034904:Lamin Type A / Q000235:genetics*; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D009426:Netherlands; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics*; D055815:Young Adult
chemical_list: C494847:LMNA protein, human; D034904:Lamin Type A