Familial hypercholesterolaemia (GMS)
Gene: APOEThe mode of inheritance of this gene has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.Created: 30 Jan 2023, 4:21 p.m. | Last Modified: 30 Jan 2023, 4:21 p.m.
Panel Version: 1.12
PMID: 34058468, reviews APOE variants found in primary dyslipidemia. Table 1 lists both monoallelic and biallelic APOE variants associated with hypercholesterolemia.Created: 24 Feb 2022, 5:38 p.m. | Last Modified: 24 Feb 2022, 5:38 p.m.
Panel Version: 1.10
Comment on phenotypes: Including hypercholesterolaemiaCreated: 2 Jul 2019, 1:19 p.m. | Last Modified: 2 Jul 2019, 1:19 p.m.
Panel Version: 1.24
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications
The APOE (NM_00041) in-frame deletion c.500_502del p.(Leu167del) has been identified in four singletons recruited to the 100KGP for FH analysis by the Wessex GMC.Created: 18 Feb 2019, 5:43 p.m.
Comment on list classification: See comments under 9th November 2017 reviewCreated: 9 Nov 2017, 9:32 a.m.
At a meeting on 7/11/17 with Prof Steve Humphries and Dr. Ellen Thomas we discussed this. There is sufficient evidence for inclusion; 4 unrelated cases (inc one large family) with hypercholesterolaemia (see above PMIDs). Considered appropriate for inclusion. Please note that the homozygous APOE4 allele (presence of Arg at 112 and 156) that is associated with an increased risk of Alzheimer's would not be expected to be tiered via this panel in view of allele frequency and the combination of two variants in a homozygous state.Created: 9 Nov 2017, 9:31 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Autosomal dominant hypercholesterolaemia
Publications
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 = 1.Created: 19 Feb 2016, 2:47 p.m.
One haplotype is associated with hypercholesterolaemia in a small proportion of homozygotes, but most homozygotes have normal cholesterol. Homozygosity for another haplotype causes increased risk for Alzheimers disease. We don't want to know about the Alzheimers risk, and the hypercholesterolaemia risk is not clinically useful information, so this gene should NOT be on the panel for FH.Created: 13 Dec 2015, 9:43 p.m.
Tag Q1_22_MOI was removed from gene: APOE.
Source NHS GMS was added to APOE. Mode of inheritance for gene APOE was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Tag Q1_22_MOI tag was added to gene: APOE.
Publications for gene: APOE were set to 11095479; 23433584; 24267230; 26802169; 16094309; 22481068; 22949395
Phenotypes for gene: APOE were changed from Hyperlipoproteinemia, type III 617347 to Hyperlipoproteinemia, type III, OMIM:617347
gene: APOE was added gene: APOE was added to Familial hypercholesterolaemia - targeted panel. Sources: Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory,Expert Review Green Mode of inheritance for gene: APOE was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: APOE were set to 11095479; 23433584; 24267230; 26802169; 16094309; 22481068; 22949395 Phenotypes for gene: APOE were set to Hyperlipoproteinemia, type III 617347