Familial hypercholesterolaemia (GMS)

Gene: APOE

The 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

Green List (high evidence)

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 hypercholesterolaemia

Created: 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

• 34058468

Green List (high evidence)

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.

Green List (high evidence)

Comment on list classification: See comments under 9th November 2017 review

Created: 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

• 22949395
• 26802169

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.

Red List (low evidence)

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.