title: Hypobetalipoproteinemia with an apparently recessive inheritance due to a "de novo" mutation of apolipoprotein B.
abstract: Familial hypobetalipoproteinemia (FHBL) is a co-dominant disorder either linked or not linked to apolipoprotein (apo) B gene. Abetalipoproteinemia (ABL) is a recessive disorder due to mutations of microsomal triglyceride transfer protein (MTP) gene. We investigated a patient with apparently recessive hypobetalipoproteinemia consistent with symptomatic heterozygous FHBL or a "mild" form of ABL. The proband had fatty liver associated with LDL-cholesterol (LDL-C) and apo B levels <5th percentile but no truncated apo B forms detectable in plasma. MTP gene sequence revealed that he was a carrier of the I128T polymorphism and an unreported amino acid substitution (V168I) unlikely to be the cause of hypobetalipoproteinemia. Apo B gene sequence showed that he was heterozygous for two single base substitutions in exon 9 and 22 resulting in a nonsense (Q294X) and a missense (R1101H) mutation, respectively. Neither of his parents carried the Q294X; his father and paternal grandmother carried the R1101H mutation. Analysis of polymorphic genetic markers excluded non-paternity. In conclusion, the proband has a "de novo" mutation of apo B gene resulting in a short truncated apo B form (apo B-6.46). Sporadic cases of FHBL with an apparently recessive transmission may be caused by "de novo" mutations of apo B gene.
authors.affiliation: Department of Biomedical Sciences, University of Modena and Reggio Emilia, Via Campi 287, I-41100 Modena, Italy.
authors.forename: Sandra
authors.initials: S
authors.lastname: Lancellotti
authors.forename: Enza
authors.initials: E
authors.lastname: Di Leo
authors.forename: Junia Y
authors.initials: JY
authors.lastname: Penacchioni
authors.forename: Fiorella
authors.initials: F
authors.lastname: Balli
authors.forename: Laura
authors.initials: L
authors.lastname: Viola
authors.forename: Stefano
authors.initials: S
authors.lastname: Bertolini
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Calandra
authors.forename: Patrizia
authors.initials: P
authors.lastname: Tarugi
mesh_terms: D000012:Abetalipoproteinemia / Q000175:diagnosis / Q000235:genetics; D001055:Apolipoproteins B / Q000097:blood / Q000737:chemistry / Q000235:genetics*; D001483:Base Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics; D002499:Centrifugation, Density Gradient; D002648:Child; D003937:Diagnosis, Differential; D004591:Electrophoresis, Polyacrylamide Gel; D005091:Exons; D005816:Genetic Complementation Test; D014644:Genetic Variation; D006801:Humans; D007009:Hypolipoproteinemias / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010641:Phenotype
chemical_list: D001055:Apolipoproteins B; D002352:Carrier Proteins; C106092:microsomal triglyceride transfer protein