Multiple linear regression analysis showed that the FH status was the only independent factor associated with apoB-48 levels, contributing to 28.7% of the variance (P < 0.0001).
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).
In this and our previous study, we show that a causal mutation in LDLR, APOB, and PCSK9 can be identified in almost all children with a definite clinical diagnosis of FH.
Familial hypercholesterolemia (FH) is an autosomal dominant disease caused by mutations in the genes for LDL receptor (LDLR), apolipoprotein B (APOB) and proprotein convertase subtilisin/kexin type9 (PCSK9).
Mutations in any of three genes (LDLR, APOB and PCSK9) are known to cause autosomal dominant FH, but a mutation can be found in only ∼40% of patients with a clinical diagnosis of FH.
Molecular analysis of FH was performed using target exome sequencing in <i>LDLR</i> (low-density lipoprotein cholesterol receptor gene), <i>APOB</i> (apolipoprotein B gene), and <i>PCSK9</i> (proprotein convertase subtilisin/kexin type 9 gene).
The study included 193 unrelated adult patients (mean age 48 ± 13 years) with clinical diagnosis of FH based on the revised DLCN score, tested sequentially for mutations in LDLR and APOB genes using bidirectional Sanger sequencing and MLPA techniques.
A putative pathogenic variant was identified in 660 heterozygous patients: LDLR (623), APOB (33), and PCSK9 (4); 8 patients presented with homozygous FH.A detection rate of 41.5% was observed.
Refinement of variant selection for the LDL cholesterol genetic risk score in the diagnosis of the polygenic form of clinical familial hypercholesterolemia and replication in samples from 6 countries.
To address this problem, we have devised a novel therapeutic concept, APO-skip, which is based on modulation of APOB splicing, and which has the potential to deliver a cost-effective, efficacious and safe therapy for FH.
Functional characterization of the LDLR, APOB and PCSK9 mutant genes associated with FH can be considered a necessary integration of its genetic diagnosis.
Mutations in four genes have been noted in patients with familial hypercholesterolemia (FH): LDL receptor (most common), apolipoprotein B (Apo B), proprotein convertase subtilin/kexin 9 (PCSK9), and low-density lipoprotein receptor adaptor protein (LDLRAP).
Metaanalysis of the weighted 6-SNP score, on the basis of polymorphisms in CELSR2 (cadherin, EGF LAG 7-pass G-type receptor 2), APOB (apolipoprotein B), ABCG5/8 [ATP-binding cassette, sub-family G (WHITE), member 5/8], LDLR (low density lipoprotein receptor), and APOE (apolipoprotein E) loci, in the independent FH/M- cohorts showed a consistently higher score in comparison to the WHII population (P < 2.2 × 10(-16)).
Here, we investigated the mode of inheritance of this mutation and confirmed that FH in this family is due to mutation only in the LDLR and not PCSK9 and ApoB genes.