title: Application of molecular genetics for diagnosing familial hypercholesterolemia in Norway: results from a family-based screening program.
abstract: A total of 119 different mutations in the low-density lipoprotein-receptor gene have so far been found to cause familial hypercholesterolemia (FH) among Norwegian patients. As of April 2003, 2390 patients from 959 unrelated families were provided with a molecular genetic diagnosis. Of these, 25.3% had xanthomas and 8.4% had xanthelasma. During the last 2-3 years, a systematic family-based program to identify close relatives of FH patients has been established. A total of 851 relatives of 188 index patients have undergone genetic testing. Four hundred seven people (47.9%) were affected, and 444 (52.1%) were unaffected. Only 41.5% of those affected were on lipid-lowering drugs, and only 6.1% had a value for total serum cholesterol below 193 mg/dL (5.0 mmol/L). A follow-up study was conducted in 146 of 407 affected relatives 6 months after genetic testing was performed. Of those already under treatment at the time of genetic testing, nonsignificant reductions of total serum cholesterol and low-density lipoprotein cholesterol of 3.2% and 7.1% were observed. Of those not under treatment who were aged 18 years and older, the corresponding reductions were 21.2% (p <.0001) and 30.0% (p <.0001), respectively. We conclude that molecular genetic methods represent a feasible and highly efficient tool in a family-based strategy to diagnose FH.
authors.affiliation: Medical Genetics Laboratory, Department of Medical Genetics, Rikshospitalet, Oslo, Norway. trond.leren@rikshospitalet.no
authors.forename: Trond P
authors.initials: TP
authors.lastname: Leren
authors.forename: Turid
authors.initials: T
authors.lastname: Manshaus
authors.forename: Unn
authors.initials: U
authors.lastname: Skovholt
authors.forename: Tove
authors.initials: T
authors.lastname: Skodje
authors.forename: Inger Esther
authors.initials: IE
authors.lastname: Nossen
authors.forename: Christél
authors.initials: C
authors.lastname: Teie
authors.forename: Stine
authors.initials: S
authors.lastname: Sørensen
authors.forename: Kari Solberg
authors.initials: KS
authors.lastname: Bakken
mesh_terms: D015415:Biomarkers / Q000097:blood; D019468:Disease Management; D005192:Family Health; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005820:Genetic Testing; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000175:diagnosis* / Q000628:therapy; D008055:Lipids / Q000097:blood; D008967:Molecular Biology; D009664:Norway / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D008055:Lipids