Identification of a second "French Canadian" LDL receptor gene deletion and development of a rapid method to detect both deletions.
Hobbs et al. (N. Engl. J. Med. 317: 734-737, 1987) reported a large deletion of approximately 10 kilobases in the 5' portion of the human low-density lipoprotein (LDL) receptor gene. This deletion affects about 60% of familial hypercholesterolemia (FH) heterozygotes in the French Canadian population. We have developed a rapid, convenient method for the detection of the deletion using double digestion with the restriction enzymes XbaI and EcoRV, or triple digestion with XbaI, EcoRV and XmnI, and a 650 bp cDNA probe, radio-labeled using a random oligonucleotide primer technique. Eighty French Canadian FH heterozygotes were screened for the presence of the deletion. Forty-seven (59%) of them were found to carry the 10 kb deletion. Using the same method, we also identified a new mutation which was found in four of the 80 (5%) FH patients. This mutation has been found to be a 5 kb deletion removing exons 2 and 3 of the LDL receptor gene, which correspond to the first two repeats of the LDL receptor binding domain. Cosegregation of the 5 kb deletion and the FH phenotype was observed in one family. Possible structure-function relationship is discussed.
Ma
Y H
YH
Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montréal, Québec, Canada.
Bétard
C
C
Roy
M
M
Davignon
J
J
Kessling
A M
AM
D002170:Canada; D002872:Chromosome Deletion; D015342:DNA Probes; D015280:DNA Restriction-Modification Enzymes; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D009154:Mutation; D010375:Pedigree; D011973:Receptors, LDL / Q000235:genetics*
D015342:DNA Probes; D015280:DNA Restriction-Modification Enzymes; D011973:Receptors, LDL