title: [Genotype-phenotype correlations in familial hypercholesterolemia].
abstract: The low-density lipoprotein (LDL) receptor gene mutations cause familial hypercholesterolemia (FH), which was characterized by increased levels of LDL cholesterol and premature coronary atherosclerosis. Molecular genetic study of FH showed extreme heterogeneity in their underlying LDL receptor gene mutations, and suggested that this heterogeneity is responsible for the variability of its clinical manifestations. Since 1988, we have identified 11 mutations (10 novel and 1 previously reported) in the LDL receptor gene among 201 unrelated FH families in Hokuriku district, Japan. However, they explained only 38.8% of the patients suggesting that a more efficient mutation screening method should be developed. Through mutation detection, a genetically-determined mild type of FH (homozygotes with relative longevity and normocholesterolemic heterozygotes) was found in a case in which exons 2 and 3 were eliminated by a 10 kb deletion (Tonami-2). In addition, cholesterol-lowering drug therapy was significantly more effective in heterozygous patients with the P664L mutation (Kanazawa-2) compared to those with a 6 kb deletion including exon 15 (Tonami-1). These observations indicate that FH patients should be managed based on the results of their gene analyses.
authors.affiliation: Second Department of Internal Medicine, School of Medicine, Kanazawa University.
authors.forename: K
authors.initials: K
authors.lastname: Kajinami
mesh_terms: D044466:Asian People; D005838:Genotype; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics*; D007564:Japan; D010641:Phenotype; D011973:Receptors, LDL / Q000235:genetics*
chemical_list: D011973:Receptors, LDL