title: Diagnosing familial hypercholesterolaemia: the relevance of genetic testing.
abstract: OBJECTIVE
  We assembled a cohort of patients with familial hypercholesterolaemia (FH) for both basic and clinical research. We used a set of established diagnostic criteria to define FH. Some put forward that a definite diagnosis of FH is made when a mutation in the LDL-receptor (LDLR) gene is identified. We therefore set out to determine in these patients whether patients with a DNA diagnosis would differ significantly from those diagnosed clinically.
  
  
  RESULTS
  We randomly selected 4000 hypercholesterolaemic patients from the Dutch Lipid Clinic network database. Phenotypical data were acquired by reviewing medical records. After review of medical records, 2400 patients could be defined as having FH. An LDLR mutation was identified in 52.3% of these patients. Patients with and without an LDLR mutation demonstrated different clinical and laboratory characteristics. Low-density lipoprotein cholesterol was higher in patients with an LDLR mutation, whereas triglycerides were higher in patients without an LDLR mutation. The phenotypic differences between the groups remained even after stratification for the presence or absence of tendon xanthomas.
  
  
  CONCLUSIONS
  Despite the use of stringent clinical criteria to define FH patients, two cohorts could be identified within our study population, namely those patients with and those without an LDLR mutation. Our findings suggest that among those without an LDLR mutation, patients with other causes of dyslipidaemia may be present. These observations underline the relevance of genetic testing in FH for clinical practice, for screening purposes, and for research involving these patients.
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Emily S
authors.initials: ES
authors.lastname: van Aalst-Cohen
authors.forename: Angelique C M
authors.initials: AC
authors.lastname: Jansen
authors.forename: Michael W T
authors.initials: MW
authors.lastname: Tanck
authors.forename: Joep C
authors.initials: JC
authors.lastname: Defesche
authors.forename: Mieke D
authors.initials: MD
authors.lastname: Trip
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Lansberg
authors.forename: Anton F H
authors.initials: AF
authors.lastname: Stalenhoef
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
mesh_terms: D000328:Adult; D015331:Cohort Studies; D005260:Female; D005817:Genetic Counseling; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D011973:Receptors, LDL / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D011973:Receptors, LDL