Deletion in the gene for the low-density-lipoprotein receptor in a majority of French Canadians with familial hypercholesterolemia

HH Hobbs, MS Brown, DW Russell… - … England Journal of …, 1987 - Mass Medical Soc
HH Hobbs, MS Brown, DW Russell, J Davignon, JL Goldstein
New England Journal of Medicine, 1987Mass Medical Soc
We found a large deletion (more than 10 kilo-bases) in the gene for the low-density-
lipoprotein receptor in 63 percent of French Canadians with heterozygous familial
hypercholesterolemia. The deletion also occurred in homozygous form in four of seven
French Canadian homozygotes. The deletion removes the promoter and first exon of the
gene, and it abolishes the production of messenger RNA for the low-density-lipoprotein
receptor. The high frequency of this mutation is presumably related to a founder effect …
Abstract
We found a large deletion (more than 10 kilo-bases) in the gene for the low-density-lipoprotein receptor in 63 percent of French Canadians with heterozygous familial hypercholesterolemia. The deletion also occurred in homozygous form in four of seven French Canadian homozygotes. The deletion removes the promoter and first exon of the gene, and it abolishes the production of messenger RNA for the low-density-lipoprotein receptor. The high frequency of this mutation is presumably related to a founder effect among the 8000 ancestors of present-day French Canadians, who have had relatively little cross-breeding with groups of other national origins.
This deletion has not been observed in any other ethnic group. It can be detected by analysis of genomic DNA from blood leukocytes, thus allowing direct diagnosis of familial hypercholesterolemia in a majority of affected French Canadians. (N Engl J Med 1987; 317: 734–7.)
The New England Journal Of Medicine