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Identification of a second “French Canadian” LDL receptor gene deletion and development of a rapid method to detect both deletions
Author(s) -
Bétard Christine,
Roy Madeleine,
Davig Jean,
Kessling Anna M.
Publication year - 1989
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/j.1399-0004.1989.tb03194.x
Subject(s) - ecorv , genetics , biology , ldl receptor , exon , microbiology and biotechnology , familial hypercholesterolemia , gene , restriction enzyme , mutation , primer (cosmetics) , restriction site , population , hindiii , lipoprotein , chemistry , medicine , biochemistry , cholesterol , environmental health , organic chemistry
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 Xbal and EcoRV, or triple digestion with Xbal, 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.