PREVALENCE AND GEOGRAPHICAL-DISTRIBUTION OF MAJOR LDL RECEPTOR GENE REARRANGEMENTS IN FINLAND

In order to determine the prevalence of major rearrangements of the lo w density lipoprotein (LDL) receptor gene in Finland. DNA samples of 1 99 unrelated Finnish patients with the heterozygous form of familial h ypercholesterolaemia (FH) were examined by Southern blot analysis. The FH-Helsinki mutation, characterized by a 9.5-kb deletion in the 3'-en d of the LDL receptor gene, was found in 75 (38%) of the patients. The prevalence of this mutation ranged from 26-58% in different areas of Finland. A striking exception was the North Karelia region, where only one out of 26 (4%) FH patients was found to carry the FH-Helsinki all ele. Two patients were found to carry other types of large nucleotide rearrangements of the LDL receptor gene. One mutation was a 7.5-kb del etion eliminating exons 7 to 10, and the other was a 13-kb deletion co vering exons 11 to 16 of the LDL receptor gene. Serum lipoprotein leve ls were very similar in each category of mutation. i.e. in patients wi th the FH-Helsinki gene, those with the two other types of deletion, a nd the remaining patients with as yet unknown types of LDL receptor ge ne defects. These results show that, even in genetically uniform popul ations, FH may be heterogeneous at the DNA level. DNA techniques enabl e an unequivocal diagnosis for almost 40% of the Finnish patients with the heterozygous form of FH.