Search results for "Familial Hypobetalipoproteinemia"

Clinical and biochemical characteristics of individuals with low cholesterol syndromes: A comparison between familial hypobetalipoproteinemia and fam…

2017

Background The most frequent monogenic causes of low plasma cholesterol are familial hypobetalipoproteinemia (FHBL1) because of truncating mutations in apolipoprotein B coding gene (APOB) and familial combined hypolipidemia (FHBL2) due to loss-of-function mutations in ANGPTL3 gene. Objective A direct comparison of lipid phenotypes of these 2 conditions has never been carried out. In addition, although an increased prevalence of liver steatosis in FHBL1 has been consistently reported, the hepatic consequences of FHBL2 are not well established. Methods We investigated 350 subjects, 67 heterozygous carriers of APOB mutations, 63 carriers of the p.S17* mutation in ANGPTL3 (57 heterozygotes and …

Association between familial hypobetalipoproteinemia and the risk of diabetes. Is this the other side of the cholesterol-diabetes connection? A syste…

2017

Statin therapy is beneficial in reducing LDL cholesterol (LDL-C) levels and cardiovascular events, but it is associated with the risk of incident diabetes mellitus (DM). Familial hypercholesterolemia (FH) is characterized by genetically determined high levels of plasma LDL-C and a low prevalence of DM. LDL-C levels seem then inversely correlated with prevalence of DM. Familial hypobetalipoproteinemia (FHBL) represents the genetic mirror of FH in terms of LDL-C levels, very low in subjects carrying mutations of APOB, PCSK9 (FHBL1) or ANGPTL3 (FHBL2). This review explores the hypothesis that FHBL might represent also the genetic mirror of FH in terms of prevalence of DM and that it is expecte…

A Novel Loss of Function Mutation of PCSK9 Gene in White Subjects With Low-Plasma Low-Density Lipoprotein Cholesterol

2007

Objectives— The PCSK9 gene, encoding a pro-protein convertase involved in posttranslational degradation of low-density lipoprotein receptor, has emerged as a key regulator of plasma low-density lipoprotein cholesterol. In African-Americans two nonsense mutations resulting in loss of function of PCSK9 are associated with a 30% to 40% reduction of plasma low-density lipoprotein cholesterol. The aim of this study was to assess whether loss of function mutations of PCSK9 were a cause of familial hypobetalipoproteinemia and a determinant of low-plasma low-density lipoprotein cholesterol in whites. Methods and Results— We sequenced PCSK9 gene in 18 familial hypobetalipoproteinemia subjects and i…

Plasma non-cholesterol sterols in primary hypobetalipoproteinemia

2011

Primary hypobetalipoproteinemia (pHBL) is characterized by plasma cholesterol levels ApoB48, and FHBL harbouring as yet unknown molecular defects. Not linked FHBL kindred are not homogeneous in terms of plasma NCS levels. NCS cannot replace genetic HBL analysis.

Familial hypobetalipoproteinemia: Analysis by next generation sequencing and identification of a novel frameshift mutation in the apoB gene

2017

Molecular diagnosis of hypobetalipoproteinemia: an ENID review.

2007

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-3…

The c.43_44insCTG variation in PCSK9 is associated with low plasma LDL-cholesterol in a Caucasian population.

2006

Abstract The genetic etiology of familial hypobetalipoproteinemia (FHBL) is unclear in the majority of cases. Mutations in apolipoprotein B (APOB) are the only confirmed causes of FHBL. Recently, loss-of-function mutations of PCSK9 gene have been shown to be associated with the hypocholesterolemia phenotype. Our primary goal was to confirm that mutations in PCSK9 could be another cause of FHBL. Using the sequencing approach, we found that the c.43_44insCTG variation in PCSK9, a common in-frame insertion in both African American and Caucasian populations, is associated with the hypocholesterolemia phenotype in three FHBL families. Then we tested whether this variation could be associated wit…

GENETIC MARKERS OF DEVELOPMENT AND PROGRESSION OF THE ATHEROSCLEROSIS. POSSIBLE ROLE OF VARIANTS THAT CHANGE THE INTERACTIONS WITH THE PROTEOGLYCANS …

2021

Homozygous familial hypobetalipoproteinemia: two novel mutations in the splicing sites of apolipoprotein B gene and review of the literature.

2015

Objective: Familial hypobetalipoproteinemia (FHBL) is autosomal codominant disorder of lipoprotein metabolism characterized by low plasma levels of total cholesterol (TC), low-density lipoproteincholesterol (LDL-C) and apolipoprotein B (apoB) below the 5 th percentile of the distribution in the population. Patients with the clinical diagnosis of homozygous FHBL (Ho-FHBL) are extremely rare and few patients have been characterized at the molecular level. Here we report the medical history and the molecular characterization of one paediatric patient with clinical features of Ho-FHBL. Methods: A one month old infant with failure to thrive, severe hypocholesterolemia and acanthocytosis was clin…

Genetics of familial hypobetalipoproteinemia

2007

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 tha…