LOW-FREQUENCY OF THE COMMON NORWEGIAN AND FINNISH LDL-RECEPTOR MUTATIONS IN SWEDISH PATIENTS WITH FAMILIAL HYPERCHOLESTEROLEMIA

Objective. To evaluate the frequency of the common Finnish and Norwegi an mutations in the low density lipoprotein (LDL) receptor gene in Swe dish patients with familial hypercholesterolaemia (FH), and to start s creening for other mutations in these patients. Ln contrast to the sit uation in Norway and Finland, where the frequency of common mutations causing the disease has been determined, very little about the mutatio n spectrum is known in Sweden. Settings and subjects. In total, 182 un related Swedish patients fulfilling clinical criteria for FH were inve stigated. Of these, 112 were identified at Huddinge University Hospita l in Stockholm, and 70 at Sahlgren's Hospital in Goteborg. They were s creened by single-strand conformation polymorphism (SSCP) for mutation s in exons 3, 4, 6 and 9 of the LDL-receptor gene and by polymerase ch ain reaction (PCR) for the most common FH mutations occurring in Finla nd, and the prevailing mutation causing familial defective apolipoprot ein B-100 (FDB). Results. Mutations in the LDL receptor were identifie d in 25 of the 182 patients.Of these, 10 represented FH-Helsinki and o ne FH-North Karelia. Other mutations identified were FH-Svartor (four patients), FH-Elverum (one patient), FH-Padova (two patients), FH-Moro cco (one patient) and FH-Algeria-1 (one patient). One patient was simu ltaneously positive for two mutations formerly described in Sweden: E2 56K (exon 6) and I402T (exon 9). Another mutation caused replacement o f one amino acid residue in exon 6 (C292Y). Two new mutations were fou nd, both in exon 6: one nonsense mutation in the codon #275 for cystei ne (FH-Huddinge, two patients), and one deletion of two base-pairs in the codon for leucine in position 254 (FH-Goteborg, one patient). The mutation for FDB was found in three patients. Conclusions. The mutatio n pattern in Swedish FH patients differs considerably from that in Fin land and Norway. The two new mutations discovered will probably cause serious functional disturbances in the LDL-receptor function. Thus far , no predominant mutation was seen in Swedish FH-patients.