Swipe om te navigeren naar een ander artikel
In the Netherlands, a screening programme was set up in 1994 in order to identify all patients with familial hypercholesterolaemia (FH). After 15 years of screening, we evaluated the geographical distribution, possible founder effects and clinical phenotype of the 12 most prevalent FH gene mutations.
Patients who carried one of the 12 most prevalent mutations, index cases and those identified between 1994 and 2009 through the screening programme and whose postal code was known were included in the study. Low-density lipoprotein cholesterol (LDL-C) levels at the time of screening were retrieved. The prevalence of identified FH patients in each postal code area was calculated and visualised in different maps.
A total of 10,889 patients were included in the study. Mean untreated LDL-C levels ranged from 4.4 to 6.4 mmol/l. For almost all mutations, a region of high prevalence could be observed. In total, 51 homozygous patients were identified in the Netherlands, of which 13 true homozygous for one of the 12 most prevalent mutations. The majority of them were living in high-prevalence areas for that specific mutation.
Phenotypes with regard to LDL-C levels varied between the 12 most prevalent FH mutations. For most of these mutations, a founder effect was observed. Our observations can have implications with regard to the efficiency of molecular screening and physician’s perception of FH and to the understanding of the prevalence and distribution of homozygous patients in the Netherlands.
Goldstein JL, Hobbs HH, Brown MS. The metabolic and molecular bases of inherited disease. New York: McGraw-Hill; 2001.
Lansberg PJ, Tuzgol S, van de Ree MA, et al. Higher prevalence of familial hypercholesterolemia than expected in adult patients of four family practices in Netherlands. Ned Tijdschr Geneeskd. 2000;144:1437–40. PubMed
Innerarity TL, Mahley RW, Weisgraber KH, et al. Familial defective apolipoprotein B-100: a mutation of apolipoprotein B that causes hypercholesterolemia. J Lipid Res. 1990;31:1337–49. PubMed
Defesche JC. Familial hypercholesterolaemia. In: Betteridge DJ, editor. Lipids and vascular disease. London: Martin Dunitz; 2000. p. 65–76.
Cobbaert C, Boerma GJ, Lindemans J. Evaluation of the Cholestech L.D.X. desktop analyser for cholesterol, HDL-cholesterol, and triacylglycerols in heparinized venous blood. Eur J Clin Chem Clin Biochem. 1994;32:391–4. PubMed
Hofman N, Postema PG, van Langen IM, et al. Genetic identification of patients and families with a long-QT syndrome: large regional differences in the result of 10 years. Ned Tijdschr Geneeskd. 2007;151:644–8. PubMed
StOEH. Annual report 2008. Amsterdam: StOEH; 2009.
Defesche JC, Van Diermen DE, Hayden MR, et al. Origin and migration of an Afrikaner founder mutation FHAfrikaner-2 (V408M) causing familial hypercholesterolemia. Gene Geogr. 1996;10:1–10. PubMed
den Dunnen JT, Antonarakis SE. Mutation nomenclature extensions and suggestions to describe complex mutations: a discussion. Hum Mutat. 2000;15:7–12. CrossRef
- Founder mutations in the Netherlands: geographical distribution of the most prevalent mutations in the low-density lipoprotein receptor and apolipoprotein B genes
D. M. Kusters
J. C. Defesche
M. N. Vissers
B. A. Hutten
J. J. P. Kastelein
- Bohn Stafleu van Loghum