Familial hypercholesterolaemia (GMS)
Gene: APOBGene 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 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 Familial Hypercholesterolemia; Familial Hypercholesterolaemia; Hypercholesterolemia, familial, 2, 144010; Hypercholesterolemia to Hypercholesterolemia, familial, 2, OMIM:144010
gene: APOB was added gene: APOB was added to Familial hypercholesterolaemia - targeted panel. Sources: Radboud University Medical Center, Nijmegen,UKGTN,Expert Review Green,Illumina TruGenome Clinical Sequencing Services,Emory Genetics Laboratory Mode of inheritance for gene: APOB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: APOB were set to 8141833; 25414277; 23433573 Phenotypes for gene: APOB were set to Familial Hypercholesterolemia; Familial Hypercholesterolaemia; Hypercholesterolemia, familial, 2, 144010; Hypercholesterolemia Mode of pathogenicity for gene: APOB was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments