Familial hypercholesterolaemia (FH) is characterized by severely elevated plasma levels of low density lipoprotein cholesterol (LDL-C) from birth that cause atherosclerotic plaque deposition in arteries and a markedly increased risk of coronary artery disease at an early age. Persons with untreated FH are at an approximately 20-fold increased risk for coronary heart disease and untreated men are at a 50% risk for a fatal or non-fatal coronary event by age 50 years [46]. FH is relatively common (prevalence 1:250) [46]. Pathogenic variants in 3 genes (LDLR, APOB and PCSK9) have been shown to underlie FH and the genetic cause is a determinant of the outcome. It has been estimated that about 95% of patients with FH carry a pathogenic variant in one of these genes, with mutations in LDLR being the most common cause. Homozygous FH is much rarer (prevalence 1:160,000 to 1:1,000,000) and most patients experience severe coronary heart disease by their mid-20s [46].
| Gene name | Transcript | Clinical sensitivity |
| LDLR | ENST00000588518.1 | 60-80% [46] |
| APOB | ENST00000233242.1 | 1-5% [46] |
| PCSK9 | ENST00000302118.5 | 0-3% [46] |
| LDLRAP1 (ARH) | ENST00000374338.4 | n/a |
| LPA | ENST00000316300 |
Clinical genetics and genomics laboratory
Ground floor (level 2), Sydney wing, Royal Brompton Hospital, Sydney Street, London, SW3 6NP
Telephone: 020 7352 8121 ext. 83009
Email: rbh-tr.genomics@nhs.net or geneticslab@rbht.nhs.uk
Opening hours: Monday to Friday, 9 am - 5 pm
Head of laboratory: Dr Deborah Morris-Rosendahl
Useful documents
Molecular genetic testing request and consent form (pdf, 431KB)
Non-NHS molecular genetic testing request and consent form (pdf, 493KB)