title: Identification of a novel mutation in the ANGPTL3 gene in two families diagnosed of familial hypobetalipoproteinemia without APOB mutation.
abstract: BACKGROUND
  Familial hypobetalipoproteinemia (FHBL), characterized by extremely low levels of plasma apolipoprotein (apo) B and cholesterol associated with low-density lipoproteins (LDLc), is considered to be an autosomal co-dominant disorder of heterogeneous origin. The main genetic disorder associated with FHBL consists of mutations in the APOB gene, while other less frequent forms are associated with mutations in NPC1L1, PCSK9, a still unidentified gene in 3p21.1-22 and, more recently, in ANGPTL3.
  
  
  METHODS
  We scanned for ANGPTL3 mutations in 4 unrelated Spanish families with FHBL criteria but negative for mutations in APOB. The entire coding region and intron-exon boundaries of the ANGPTL3 gene were amplified and sequenced.
  
  
  RESULTS
  Two probands were positive for the same frameshift mutation, a deletion of 5 bp in codon 121 in ANGPTL3, which produces a truncated protein of 122 residues. This mutation in homozygosis was associated in both families with combined hypolipidemia, characterized by low plasma apoB, low total, LDL and HDL cholesterol and low triglycerides.
  
  
  CONCLUSIONS
  We confirm the existence of a new phenotype of FHBL, denominated familial combined hypolipidemia, which consist of a biochemical phenotype of low LDLc, low apoB, low TG and, unlike APOB mutations, low HDL cholesterol, due to a loss-of-function mutation in ANGPTL3.
authors.affiliation: Institut d'Investigació Biomèdica Sant Pau, Barcelona, Spain.
authors.forename: Jesús M
authors.initials: JM
authors.lastname: Martín-Campos
authors.forename: Rosa
authors.initials: R
authors.lastname: Roig
authors.forename: Carme
authors.initials: C
authors.lastname: Mayoral
authors.forename: Silvia
authors.initials: S
authors.lastname: Martinez
authors.forename: Gertrudis
authors.initials: G
authors.lastname: Martí
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Arroyo
authors.forename: Josep
authors.initials: J
authors.lastname: Julve
authors.forename: Francisco
authors.initials: F
authors.lastname: Blanco-Vaca
mesh_terms: D000091303:Angiopoietin-Like Protein 3; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins / Q000235:genetics*; D001055:Apolipoproteins B / Q000235:genetics; D006801:Humans; D006995:Hypobetalipoproteinemias / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation; D010641:Phenotype
chemical_list: C479896:ANGPTL3 protein, human; D000091303:Angiopoietin-Like Protein 3; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; D001055:Apolipoproteins B