Familial hypercholesterolaemia
Gene: APOE
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, 5:40 p.m. | Last Modified: 24 Feb 2022, 5:40 p.m.
Panel Version: 1.28
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.
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 was removed from gene: APOE.
Tag Q1_22_MOI tag was added to gene: APOE.
Publications for gene: APOE were set to 23433584; 22949395; 26802169; 11095479; 16094309; 22481068; 24267230
Phenotypes for gene: APOE were changed from Autosomal dominant hypercholesterolaemia to Hyperlipoproteinemia, type III 617347
Publications for gene: APOE were set to PMID: 23433584; 22949395; 26802169
Phenotypes for APOE were set to Autosomal dominant hypercholesterolaemia
Publications for APOE were set to PMID: 23433584; 22949395; 26802169
Mode of inheritance for APOE was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
This gene has been classified as Green List (High Evidence).
This gene has been classified as Red List (Low Evidence).
This gene has been classified as Red List (Low Evidence).
APOE was added to Familial hypercholesterolaemiapanel. Source: Emory Genetics Laboratory
APOE was added to Familial hypercholesterolaemiapanel. Source: Radboud University Medical Center, Nijmegen
APOE was added to Familial hypercholesterolaemiapanel. Source: Radboud University Medical Center, Nijmegen
APOE was added to Familial hypercholesterolaemiapanel. Sources: Eligibility statement prior genetic testing