Three novel small deletion mutations of the LDL receptor gene in Korean patients with familial hypercholesterolemia

The low-density lipoprotein (LDL) receptor gene from 80 unrelated Korean pa tients with familial hypercholesterolemia (FH) was analyzed to screen for s mall structural rearrangements that could not be detected by Southern blot hybridization. Three different small deletions were detected in exon 11 of 3 FH patients and were characterized by DNA sequence analysis. Of them two mutations are in-frame 36-bp (FH 1) and 9-bp (FH 34) deletions that result in the loss of twelve amino acids (from Met(510) to Ile(521)) and three ami no acids (Thr(513), Asp(514) and Trps(515)), respectively. Both mutations a re located in the third of the five YWTD motifs of the LDL receptor gene. T he third mutation (FH 400) is a 2-bp deletion that shifts the translational reading frame and results bp deletion can be explained by the formation of a hairpin-loop structure mediated by inverted repeat sequences. On the oth er hand, the mechanism responsible for the 9- and the 2-bp deletions is pro bably strand-slippage mispairing mediated by short direct repeats. All of t hese three deletions are novel mutations. Each of the three deletions was d etected only in a single pedigree out of 80 FH families analyzed.