title: Analysis of the Afrikaner mutation in exon 9 of the low-density lipoprotein receptor gene in a large Dutch kindred suffering from familial hypercholesterolaemia.
abstract: Familial hypercholesterolaemia (FH) is the most common genetic metabolic disorder, affecting about 1 in 500 persons in the general population. With novel techniques, it is possible to identify the molecular defects underlying FH in the gene coding for the low-density lipoprotein (LDL) receptor, thereby confirming the diagnosis of FH. In this study we present a large family with a specific mutation in exon 9 of the LDL-receptor gene (an Afrikaner mutation) and we demonstrate that by a large-scale case-finding study in this family, carriers of such a mutation can be detected. Of 63 family members, 13 were shown to be at risk for cardiovascular disease as judged by their lipoprotein profile or the presence of the Afrikaner mutation. Two persons were detected, affected with a dyslipidaemia other than FH. Medical management was initiated in order to reduce the high cardiovascular risk associated with this disorder.
authors.affiliation: Centre for Haemostasis, Thrombosis, Atherosclerosis and Inflammation Research, Academic Medical Centre, Amsterdam, Netherlands.
authors.forename: J C
authors.initials: JC
authors.lastname: Defesche
authors.forename: P J
authors.initials: PJ
authors.lastname: Lansberg
authors.forename: P W
authors.initials: PW
authors.lastname: Reymer
authors.forename: R J
authors.initials: RJ
authors.lastname: Lamping
authors.forename: J J
authors.initials: JJ
authors.lastname: Kastelein
mesh_terms: D001483:Base Sequence; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009426:Netherlands; D010375:Pedigree; D017354:Point Mutation; D011973:Receptors, LDL / Q000235:genetics*
chemical_list: D011973:Receptors, LDL