Familial hypercholesterolaemia (GMS)

Gene: APOB

Gene part of the Global Lipid Genetic Consortium 12-SNP LDL-C gene score calculation (Talmud et al, 2013, PMID:23433573); Gene part of the 6-SNP LDL-C gene score calculation (Futema et al, 2015, PMID:25414277).

Created: 8 Oct 2019, 8:17 p.m. | Last Modified: 8 Oct 2019, 8:17 p.m.

Panel Version: 0.3

For 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 blood

Created: 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.

Green List (high evidence)

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

Green List (high evidence)

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 cholesterol

Created: 24 Nov 2015, 4:34 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
hypercholesterolaemia; elevated LDL-Cholesterol

Publications

• Familial defective apolipoprotein B-100: a review, including some comparisons with familial hypercholesterolaemia. Myant NB. Atherosclerosis. 1993 Dec
• 104(1-2):1-18. (8141833)

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