Familial hypercholesterolaemia
Gene: APOBFor FH
• Monoallelic
• Mostly missense variants
• Terminating variants unlikely to be involved
• Prevents the LDL particle from binding with cell surface receptors (LDLR)
• Increased levels of cholesterol in bloodCreated: 30 Sep 2019, 3:59 p.m. | Last Modified: 30 Sep 2019, 3:59 p.m.
Panel Version: 1.25
Comment on mode of pathogenicity: Limited list of missense variants (only 1 or 2)Created: 28 Jun 2016, 12:26 p.m.
On the Inherited Cardiac Condition Genes panel for Familial Hypercholesterolaemia reported in: Development of a Comprehensive Sequencing Assay for Inherited Cardiac Condition Genes, Pua et al, Journal of Cardiovascular Translational Research, online Feb 2016 (doi:10.1007/s12265-016-9673-5). The panel contains disease-causing, putatively pathogenic, research and phenocopy genes, and it is unclear from the publication whether this gene falls into the disease-causing category. No. of mutations indicated in supplemental table = 35.Created: 19 Feb 2016, 2:47 p.m.
Loss-of-function variants cause low cholesterol - not relevant for this phenotype.
Only 1 or 2 mutations cause FH: R3527Q/W and possibly a milder phenotype with R3558C (although this is disputed and may be lower penetrance).Created: 2 Dec 2015, 10:05 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Variants in this GENE are reported as part of current diagnostic practice
in the UK about 5% of patients with monogenic FH have one particular mutation in the APOB gene which is p.(R3527Q)Created: 24 Nov 2015, 4:45 p.m.
truncation mutations cause hypoapoB and low levels of LDL and total cholesterolCreated: 24 Nov 2015, 4:34 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
hypercholesterolaemia; elevated LDL-Cholesterol
Publications
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Variants in this GENE are reported as part of current diagnostic practice
Phenotypes for gene: APOB were changed from Gene part of the Global Lipid Genetic Consortium 12-SNP LDL-C gene score calculation (Talmud et al, 2013); Gene part of the 6-SNP LDL-C gene score calculation (Futema et al, 2015); Ag linked Hypobetalipoproteinemia; Hypobetalipoproteinemia, normotriglyceridemic; Hypercholesterolemia, due to ligand-defective apo B, 144010; Familial Hypercholesterolemia; Hypercholesterolemia; Familial Hypercholesterolaemia to Hypercholesterolemia, familial, 2, OMIM:144010
This gene has been classified as Green List (High Evidence).
Mode of pathogenicity for APOB was changed to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Mode of inheritance for APOB was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
APOB was added to Familial hypercholesterolaemiapanel. Source: UKGTN
APOB was added to Familial hypercholesterolaemiapanel. Source: Emory Genetics Laboratory
Model of inheritance for gene APOB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
APOB was added to Familial hypercholesterolaemiapanel. Source: Illumina TruGenome Clinical Sequencing Services
APOB was added to Familial hypercholesterolaemiapanel. Source: Radboud University Medical Center, Nijmegen
APOB was added to Familial hypercholesterolaemiapanel. Source: Eligibility statement prior genetic testing
APOB was added to Familial hypercholesterolaemiapanel. Sources: Eligibility statement prior genetic testing