title: The genetics and screening of familial hypercholesterolaemia.
abstract: Familial Hypercholesterolaemia is an autosomal, dominant genetic disorder that leads to elevated blood cholesterol and a dramatically increased risk of atherosclerosis. It is perceived as a rare condition. However it affects 1 in 250 of the population globally, making it an important public health concern. In communities with founder effects, higher disease prevalences are observed.We discuss the genetic basis of familial hypercholesterolaemia, examining the distribution of variants known to be associated with the condition across the exons of the genes LDLR, ApoB, PCSK9 and LDLRAP1. We also discuss screening programmes for familial hypercholesterolaemia and their cost-effectiveness. Diagnosis typically occurs using one of the Dutch Lipid Clinic Network (DCLN), Simon Broome Register (SBR) or Make Early Diagnosis to Prevent Early Death (MEDPED) criteria, each of which requires a different set of patient data. New cases can be identified by screening the family members of an index case that has been identified as a result of referral to a lipid clinic in a process called cascade screening. Alternatively, universal screening may be used whereby a population is systematically screened.It is currently significantly more cost effective to identify familial hypercholesterolaemia cases through cascade screening than universal screening. However, the cost of sequencing patient DNA has fallen dramatically in recent years and if the rate of progress continues, this may change.
authors.affiliation: Northern Ireland Centre for Stratified Medicine, Ulster University, C-TRIC, Altnagelvin Hospital Campus, Derry, Co Londonderry, Northern Ireland, BT47 6SB, UK.
authors.forename: Raymond
authors.initials: R
authors.lastname: Henderson
authors.affiliation: Department of Clinical Chemistry, Altnagelvin Hospital, Western Health and Social Care Trust, Londonderry, Northern Ireland, BT47 6SB, UK.
authors.forename: Maurice
authors.initials: M
authors.lastname: O'Kane
authors.affiliation: Northern Ireland Centre for Stratified Medicine, Ulster University, C-TRIC, Altnagelvin Hospital Campus, Derry, Co Londonderry, Northern Ireland, BT47 6SB, UK.
authors.forename: Victoria
authors.initials: V
authors.lastname: McGilligan
authors.affiliation: Northern Ireland Centre for Stratified Medicine, Ulster University, C-TRIC, Altnagelvin Hospital Campus, Derry, Co Londonderry, Northern Ireland, BT47 6SB, UK. s.watterson@ulster.ac.uk.
authors.forename: Steven
authors.initials: S
authors.lastname: Watterson
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D001055:Apolipoproteins B / Q000235:genetics; D005091:Exons; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000175:diagnosis / Q000235:genetics*; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000235:genetics; D011973:Receptors, LDL / Q000235:genetics; D012697:Serine Endopeptidases / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D001055:Apolipoproteins B; C573412:LDLR protein, human; C469745:LDLRAP1 protein, human; D011973:Receptors, LDL; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases
keywords: CHD; CVD; FH; Familial hypercholesterolaemia; atherosclerosis; cascade screening; cholesterol; screening; universal screening