2 NOVEL FRAMESHIFT MUTATIONS ASSOCIATED WITH THE PRESENCE OF DIRECT REPEATS OF THE LDL RECEPTOR GENE IN FAMILIAL HYPERCHOLESTEROLEMIA

Two novel frameshift mutations were detected in the mutant LDL recepto r genes responsible for familial hypercholesterolemia. One was a 5-bp insertion at codon 395 in exon 9, and the other was a one nucleotide d eletion at codon 531 in exon 11. Both mutations alter the reading fram e and consequently produce a premature stop codon in the region of the mature LDL receptor homologous to the epidermal growth factor (EGF) p recursor. With regard to the mechanism responsible for the generation of these frameshift mutations, strand slipped mispairing mediated by s hort direct repeats is considered to be the most likely. The findings seem to support the hypothesis that a short direct repeat in DNA seque nce can have a profound influence on the stability of a given gene and promote human gene mutations.