Premium
The Δ>15 Kb deletion French Canadian founder mutation in familial hypercholesterolemia: rapid polymerase chain reaction‐based diagnostic assay and prevalence in Quebec
Author(s) -
Simard LR,
Viel J,
Lambert M,
Paradis G,
Levy E,
Delvin EE,
Mitchell GA
Publication year - 2004
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.0009-9163.2004.00223.x
Subject(s) - familial hypercholesterolemia , alu element , genetics , exon , biology , population , ldl receptor , polymerase chain reaction , breakpoint , founder effect , allele , mutation , gene , microbiology and biotechnology , human genome , medicine , lipoprotein , genome , cholesterol , haplotype , endocrinology , chromosomal translocation , environmental health
Approximately one in 500 individuals in Western population has autosomal dominant familial hypercholesterolemia due to mutations in the low‐density lipoprotein receptor ( LDLR ) gene. Screening for these mutations is hampered by their large number, except in founder populations. We identified the breakpoint of the >15 kb deletion involving the LDLR gene promoter and exon 1, responsible for more than 60% of French Canadian hypercholesterolemia cases, as well as the breakpoint of the 5 kb deletion of exons 2 and 3 that accounts for an additional 5% of cases. Both deletions appear to be because of homologous recombination by unequal crossing‐over between the left arms of Alu repeats. Using RepeatMasker, we determined that 55% of the LDLR gene is composed of Alu elements; thus, it is not surprising that most LDLR rearrangements involve at least one Alu. Furthermore, we developed a rapid polymerase chain reaction‐based assay for the French Canadian‐1 (>15 kb) and French Canadian‐5 (5 kb) hypercholesterolemia alleles. Screening a representative population sample of 943 French Canadian youths whose LDL cholesterol levels were above the 50th percentile allowed us to estimate the prevalence of the >15 kb allele as 0.11% (95% confidence interval, 0.03–0.38).