title: Hypobetalipoproteinemia associated with apo B-48.4, a truncated protein only 14 amino acids longer than apo B-48.
abstract: Familial hypobetalipoproteinemia is an autosomal codominant trait that can be caused by mutations in the apo B gene. Here we report a novel apo B gene mutation causing hypobetalipoproteinemia, that is associated with the synthesis of a truncated apo B protein in a young healthy male subject and his mother. The mutation is an A deletion at position 6627 of the apo B cDNA leading to a truncated protein of 2166 amino acids (apo B-48.4). This truncated apo B was detected mainly in VLDL, LDL and in trace amounts in HDL, but not in the lipoprotein deficient plasma fraction. Affected family members present with elevated levels of HDL-cholesterol, mainly due to an increase in HDL2 particles. Postprandial triglycerides and retinyl esters in the d < 1.006 g/ml lipoprotein in the proband showed a normal response to an oral fat load compared to a group of eight matched healthy controls. In summary this novel mutation is associated with hypobetalipoproteinemia with a normal fat absorption as expected for a protein with a length similar to that of apo B-48.
authors.affiliation: Laboratory of Lipoprotein Metabolism and Atherosclerosis, Istituto Scientifico H San Raffaele, Milan, Italy. giacomo@instmed.ks.se
authors.forename: G
authors.initials: G
authors.lastname: Ruotolo
authors.forename: T
authors.initials: T
authors.lastname: Zanelli
authors.forename: C
authors.initials: C
authors.lastname: Tettamanti
authors.forename: F
authors.initials: F
authors.lastname: Ragogna
authors.forename: M
authors.initials: M
authors.lastname: Parlavecchia
authors.forename: F
authors.initials: F
authors.lastname: Viganò
authors.forename: A L
authors.initials: AL
authors.lastname: Catapano
mesh_terms: D000328:Adult; D000368:Aged; D016632:Apolipoprotein A-I / Q000097:blood; D016633:Apolipoprotein A-II / Q000097:blood; D053283:Apolipoprotein B-48; D053304:Apolipoprotein C-II; D053305:Apolipoprotein C-III; D001055:Apolipoproteins B / Q000032:analysis / Q000097:blood / Q000737:chemistry / Q000235:genetics*; D001056:Apolipoproteins C / Q000097:blood; D001057:Apolipoproteins E / Q000097:blood / Q000235:genetics; D001483:Base Sequence; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood / Q000235:genetics; D008078:Cholesterol, LDL / Q000097:blood / Q000235:genetics; D015243:Cholesterol, VLDL / Q000097:blood / Q000235:genetics; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D005192:Family Health; D005260:Female; D017353:Gene Deletion; D006801:Humans; D006995:Hypobetalipoproteinemias / Q000235:genetics*; D007120:Immunochemistry; D008297:Male; D008875:Middle Aged; D009035:Mothers; D009842:Oligopeptides / Q000737:chemistry / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics / Q000502:physiology; D012967:Sodium Dodecyl Sulfate; D014280:Triglycerides / Q000097:blood
chemical_list: D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D053283:Apolipoprotein B-48; D053304:Apolipoprotein C-II; D053305:Apolipoprotein C-III; D001055:Apolipoproteins B; D001056:Apolipoproteins C; D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D018076:DNA, Complementary; D009842:Oligopeptides; D014280:Triglycerides; D012967:Sodium Dodecyl Sulfate; D002784:Cholesterol