title: Clinical experience of scoring criteria for Familial Hypercholesterolaemia (FH) genetic testing in Wales.
abstract: OBJECTIVE
  Familial Hypercholesterolaemia (FH) is caused by mutations in genes of the Low Density Lipoprotein (LDL) receptor pathway. A definitive diagnosis of FH can be made by the demonstration of a pathogenic mutation. The Wales FH service has developed scoring criteria to guide selection of patients for DNA testing, for those referred to clinics with hypercholesterolaemia. The criteria are based on a modification of the Dutch Lipid Clinic scoring criteria and utilise a combination of lipid values, physical signs, personal and family history of premature cardiovascular disease. They are intended to provide clinical guidance and enable resources to be targeted in a cost effective manner.
  
  
  METHODS
  623 patients who presented to lipid clinics across Wales had DNA testing following application of these criteria.
  
  
  RESULTS
  The proportion of patients with a pathogenic mutation ranged from 4% in those scoring 5 or less up to 85% in those scoring 15 or more. LDL-cholesterol was the strongest discriminatory factor. Scores gained from physical signs, family history, coronary heart disease, and triglycerides also showed a gradient in mutation pick-up rate according to the score.
  
  
  CONCLUSIONS
  These criteria provide a useful tool to guide selection of patients for DNA testing when applied by health professionals who have clinical experience of FH.
authors: Wales Heart Research Institute, Cardiff University School of Medicine, University Hospital of Wales, Cardiff CF14 4XN, UK.
authors: K
authors: K
authors: Haralambos
authors: Wales FH Service c/o Cardiff and Vale University Health Board, UK.
authors: S D
authors: SD
authors: Whatley
authors: Wales FH Service c/o Cardiff and Vale University Health Board, UK.
authors: R
authors: R
authors: Edwards
authors: Wales FH Service c/o Cardiff and Vale University Health Board, UK.
authors: R
authors: R
authors: Gingell
authors: Wales FH Service c/o Cardiff and Vale University Health Board, UK.
authors: D
authors: D
authors: Townsend
authors: Wales Heart Research Institute, Cardiff University School of Medicine, University Hospital of Wales, Cardiff CF14 4XN, UK.
authors: P
authors: P
authors: Ashfield-Watt
authors: CTMM-TraIT Center for Translational Molecular Medicine, High Tech Campus 84, 5656 AG Eindhoven, The Netherlands.
authors: P
authors: P
authors: Lansberg
authors: Wales FH Service c/o Cardiff and Vale University Health Board, UK.
authors: D B N
authors: DB
authors: Datta
authors: Wales Heart Research Institute, Cardiff University School of Medicine, University Hospital of Wales, Cardiff CF14 4XN, UK. Electronic address: ian.mcdowell@wales.nhs.uk.
authors: I F W
authors: IF
authors: McDowell
mesh_terms: D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D053299:Apolipoprotein B-100 / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004252:DNA Mutational Analysis; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018579:Patient Selection; D010375:Pedigree; D010641:Phenotype; D011237:Predictive Value of Tests; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000235:genetics*; D011973:Receptors, LDL / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D012697:Serine Endopeptidases / Q000235:genetics*; D014280:Triglycerides / Q000097:blood; D014852:Wales / Q000453:epidemiology
chemical_list: C569471:APOB protein, human; D000924:Anticholesteremic Agents; D053299:Apolipoprotein B-100; D015415:Biomarkers; D008078:Cholesterol, LDL; D005819:Genetic Markers; C573412:LDLR protein, human; D011973:Receptors, LDL; D014280:Triglycerides; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases
keywords: Cholesterol; Criteria; Diagnosis; Familial Hypercholesterolaemia; Genetics