title: Identification of mutations in the apolipoprotein B-100 gene and in the PCSK9 gene as the cause of hypocholesterolemia.
abstract: BACKGROUND
  Characterization of the normally occurring mutations as the cause of hypocholesterolemia may increase our understanding of the normal lipid metabolism.
  
  
  METHODS
  DNA from 93 unrelated hypocholesterolemic subjects with a mean (+/-SD) value for total serum cholesterol of 3.3 (+/-0.5) mmol/l) were subjected to DNA sequencing of the individual exons of the apolipoprotein B-100 (apoB-100) gene and of the proprotein convertase subtilisin/kexin 9 (PCSK9) gene. The same analyses were also performed in 23 unrelated subjects with autosomal dominant hypercholesterolemia who had unusually low levels of total serum cholesterol.
  
  
  RESULTS
  Of the 93 hypocholesterolemic subjects, 9 subjects (9.7%) were heterozygous for a truncating mutation in the apoB-100 gene and six subjects (6.5%) were heterozygous for a loss-of-function mutation in the PCSK9 gene. Of the 23 subjects with autosomal dominant hypercholesterolemia, four subjects (17.4%) were heterozygous for mutations in the apoB-100 gene.
  
  
  CONCLUSIONS
  Truncating mutations in the apoB-100 gene are slightly more common as the cause of hypocholesterolemia compared to loss-of-function mutations in the PCSK9 gene. It appears that mutations in the apoB-100 gene may completely normalize the lipid profile in subjects with autosomal dominant hypercholesterolemia, whereas loss-of-function mutations in the PCSK9 gene do not have a sufficient cholesterol-lowering capacity.
authors: Medical Genetics Laboratory, Department of Medical Genetics, Rikshospitalet University Hospital, NO 0027 Oslo, Norway. trond.leren@rikshospitalet.no
authors: Trond P
authors: TP
authors: Leren
authors: Knut Erik
authors: KE
authors: Berge
mesh_terms: D000328:Adult; D053299:Apolipoprotein B-100 / Q000235:genetics*; D002784:Cholesterol / Q000097:blood* / Q000172:deficiency*; D005091:Exons / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases / Q000235:genetics*
chemical_list: D053299:Apolipoprotein B-100; D002784:Cholesterol; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases