title: High frequency of APOB gene mutations causing familial hypobetalipoproteinaemia in patients of Dutch and Spanish descent.
abstract: BACKGROUND
  Familial hypobetalipoproteinaemia (FHBL) is an autosomal co-dominant hereditary disorder of lipoprotein metabolism characterised by decreased low density lipoprotein (LDL) cholesterol and apolipoprotein B (APOB) plasma levels. High levels of plasma APOB and LDL cholesterol are strong predictors for risk of cardiovascular disease (CVD), while individuals with low APOB and LDL cholesterol levels are thought to have lower than average risk for CVD, and in fact, heterozygous FHBL patients appear to be asymptomatic.
  
  
  METHODS
  Rather than identifying truncated APOB proteins in plasma fractions separated by gel electrophoresis, which will miss any mutations in proteins smaller than 30 kb, we analysed the APOB gene directly, using PCR.
  
  
  RESULTS
  We identified nine different mutations, six of which are novel. Each mutation showed complete co-segregation with the FHBL phenotype in the families, and statistically significant differences between carriers and non-carriers were found for plasma total, LDL, and HDL cholesterol, triglycerides, and APOB levels, but not for APOA1 levels. All carriers of an APOB mutation were completely free from CVD.
  
  
  CONCLUSIONS
  Prolonged low levels of LDL cholesterol and elevated levels of HDL cholesterol may reduce the progression of atherosclerotic disease, but this has not been unequivocally shown that this is indeed the case in individuals with FHBL, and is the subject of a current study.
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: S W
authors.initials: SW
authors.lastname: Fouchier
authors.forename: R R
authors.initials: RR
authors.lastname: Sankatsing
authors.forename: J
authors.initials: J
authors.lastname: Peter
authors.forename: S
authors.initials: S
authors.lastname: Castillo
authors.forename: M
authors.initials: M
authors.lastname: Pocovi
authors.forename: R
authors.initials: R
authors.lastname: Alonso
authors.forename: J J P
authors.initials: JJ
authors.lastname: Kastelein
authors.forename: J C
authors.initials: JC
authors.lastname: Defesche
mesh_terms: D000293:Adolescent; D000328:Adult; D001055:Apolipoproteins B / Q000097:blood / Q000235:genetics*; D002648:Child; D002784:Cholesterol / Q000097:blood; D015331:Cohort Studies; D005260:Female; D014644:Genetic Variation; D006801:Humans; D006995:Hypobetalipoproteinemias / Q000097:blood / Q000235:genetics*; D008077:Lipoproteins, LDL / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D017354:Point Mutation; D017422:Sequence Analysis, DNA; D014280:Triglycerides / Q000097:blood; D044465:White People
chemical_list: D001055:Apolipoproteins B; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D014280:Triglycerides; D002784:Cholesterol