Genetics of familial hypobetalipoproteinemia

Abstract

Primary hypobetalipoproteinemias include three monogenic disorders: the relatively frequent codominant familial hypobetalipoproteinemia (FHBL), the rare recessive conditions abetalipoproteinemia (ABL) and chylomicron retention disease (CMRD). Approximately 50% of FHBL patients are carriers of mutations in the APOB gene, mostly causing the formation of truncated forms of ApoB. In some kindred, FHBL is linked to a locus on chromosome 3 (3p21), but the candidate gene is still unknown. Recently, a FHBL-like phenotype was observed in carriers of mutations of the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene causing loss-of-function of the encoded protein, a proprotein convertase that regulates LDL-receptor number in the liver. Inactivation of the PCSK9 protein is associated with an increased number of LDL receptors and increased receptor-mediated hepatic uptake of plasma LDL. ABL and CMRD are due to mutations in the microsomal triglyceride transfer protein and Sar1-ADP-ribosylation GTPase 2 genes, which affect assembly and secretion of ApoB-containing lipoproteins. In this review we present the current information on the genetics and pathophysiology of these disorders affecting either the secretion or the catabolism of ApoB-containing lipoproteins

Non-alcoholic fatty liver disease in a pediatric patient with heterozygous familial hypobetalipoproteinemia due to a novel APOB variant: a case report and systematic literature review

“…Variants in the APOB gene are the main cause of FHBL. Additionally, less frequent variants in the PCSK9 gene have also been associated with the disease ( 5 , 6 ). Most variants in the APOB gene cause the formation of truncated forms of apoB, which depending on the length may or may not be secreted into the plasma ( 7 , 8 ).…”