title: Molecular diagnosis of hypobetalipoproteinemia: an ENID review.
abstract: Primary hypobetalipoproteinemia (HBL) includes a group of genetic disorders: abetalipoproteinemia (ABL) and chylomicron retention disease (CRD), with a recessive transmission, and familial hypobetalipoproteinemia (FHBL) with a co-dominant transmission. ABL and CRD are rare disorders due to mutations in the MTP and SARA2 genes, respectively. Heterozygous FHBL is much more frequent. FHBL subjects often have fatty liver and, less frequently, intestinal fat malabsorption. FHBL may be linked or not to the APOB gene. Most mutations in APOB gene cause the formation of truncated forms of apoB which may or may be not secreted into the plasma. Truncated apoBs with a size below that of apoB-30 are not detectable in plasma; they are more frequent in patients with the most severe phenotype. Only a single amino acid substitution (R463W) has been reported as the cause of FHBL. Approximately 50% of FHBL subjects are carriers of pathogenic mutations in APOB gene; therefore, a large proportion of FHBL subjects have no apoB gene mutations or are carriers of rare amino acid substitutions in apoB with unknown effect. In some kindred FHBL is linked to a locus on chromosome 3 (3p21) but the candidate gene is unknown. Recently a FHBL plasma lipid phenotype was observed in carriers of mutations of the PCSK9 gene causing loss of function of the encoded protein, a proprotein convertase which regulates LDL-receptor number in the liver. Inactivation of this enzyme is associated with an increased LDL uptake and hypobetalipoproteinemia. HBL carriers of PCSK9 mutations do not develop fatty liver disease.
authors.affiliation: Department of Biomedical Sciences, University of Modena e Reggio Emilia, Via Campi 287, I-41100 Modena, Italy. tarugi@unimore.it
authors.forename: Patrizia
authors.initials: P
authors.lastname: Tarugi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Averna
authors.forename: Enza
authors.initials: E
authors.lastname: Di Leo
authors.forename: Angelo B
authors.initials: AB
authors.lastname: Cefalù
authors.forename: Davide
authors.initials: D
authors.lastname: Noto
authors.forename: Lucia
authors.initials: L
authors.lastname: Magnolo
authors.forename: Luigi
authors.initials: L
authors.lastname: Cattin
authors.forename: Stefano
authors.initials: S
authors.lastname: Bertolini
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Calandra
mesh_terms: D000012:Abetalipoproteinemia / Q000175:diagnosis / Q000235:genetics; D001055:Apolipoproteins B / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D052476:Hypobetalipoproteinemia, Familial, Apolipoprotein B / Q000175:diagnosis / Q000235:genetics; D008297:Male; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
chemical_list: D001055:Apolipoproteins B; D002352:Carrier Proteins; C106092:microsomal triglyceride transfer protein