The Finnish type of the LDL receptor gene mutation: molecular characterization of the deleted gene and the corresponding mRNA

Abstract

In one third of Finnish patients with the heterozygous form of familial hypercholesterolemia the disease is due to a gross deletion at the 3'-end of the LDL receptor gene. The present study demonstrates that an 8-kb deletion completely eliminates exons 16 and 17 and a part of exon 18. Cloning and partial sequencing of a DNA fragment from the mutated allele indicated that the 5'-boundary of the deletion lies within intron 15 while the 3'-breakpoint is located at nucleotide 3390 in exon 18. RNA blot hybridization studies revealed that the mutated allele encodes a truncated 4.2 kb mRNA (normal, 5.3 kb). This type of mutation has not been reported in other ethnic groups.