RAPID RESTRICTION FRAGMENT ANALYSIS FOR SCREENING 4-POINT MUTATIONS OF LOW-DENSITY-LIPOPROTEIN RECEPTOR GENE IN FRENCH-CANADIANS

Familial hypercholesterolemia (FH) has an estimated frequency of 1:154 among French Canadians in Northeastern Quebec, compared with 1:500 in most other populations, FH is caused by numerous mutations of the low -density lipoprotein (LDL) receptor gene, but only six well-characteri zed mutations are known to cause FH in French Canadians. High prevalen ce of the phenotype, along with a limited number of mutations in this population, provides a unique opportunity to study genotype-phenotype variation. Since the current methods for detection of point mutations in this population use complicated approaches, we report polymerase ch ain reaction (PCR)-based restriction fragment analysis to detect- all four point mutations. This approach provides a rapid diagnosis and is suitable to screen large number of samples for studies in genetic epid emiology; it should be useful in identifying FH in other populations b earing the same mutations. (C) 1995 Wiley-Liss, Inc.