Detection of a novel mutation (stop 468) in exon 10 of the low-density lipoprotein receptor gene causing familial hypercholesterolemia among French Canadians

Association of Specific LDL Receptor Gene Mutations With Differential Plasma Lipoprotein Response to Simvastatin in Young French Canadians With Heterozygous Familial Hypercholesterolemia

“…2 Eleven mutations in the LDL receptor gene are responsible for more than 90% of the heterozygous FH in French Canadian patients, defined on the basis of clinical and biochemical criteria. [3][4][5] Three of those mutations, a deletionϾ15 kb (⌬Ͼ15 kb) at the 5Ј end of the gene and 2 missense mutations in exons 3 (W66G) and 14 (C646Y), are present in approximately 56%, 18%, and 6%, respectively, of FH patients who attend our lipid clinic in Québec city. The ⌬Ͼ15 kb is a class I mutation and fails to produce immunoprecipitable LDL receptor protein.…”

Identification of three mutations in the low-density lipoprotein receptor gene causing familial hypercholesterolemia among French Canadians

“…The relative frequency of the three mutations described in the present study was then calculated in a cohort of 48 unrelated FC children (2-18 years old) with suspected heterozygous FH based on the following common criteria: plasma LDL-cholesterol concentrations above the 95th percentile for age and sex, premature coronary artery disease (below age 60 years), and presence of tendinous xanthomas in a first-or second-degree relative. All these children were negative for the six previously known FC Mutations in the LDL receptor gene (Simard et al, 1994) and were then screened for the three mutations. The ApoB 3500 mutation (Soria et al, 1989) was not found in any of the 15 adult FH patients or in any of the 48 children, as determined by the assay that was previously described (Hansen et al, 1991).…”

“…Selective polymerase chain reaction (PCR) amplification of each individual 18 exons, the exonintron splicing boundaries, and 290 bp of the 5 ' noncoding region of the LDL receptor gene were performed using primers previously described (Simard et al, 1994). For SSCP analysis, [35S]dATP was used for labeling PCR fragments.…”

“…Gels were dried and exposed to X-ray film. DNA sequencing of the exons displaying aberrant electrophoretic patterns by SSCP analysis were performed as previously described (Simard et al, 1994).…”

“…In the province of Quebec, the prevalence of homozygous FH is approximately sixfold higher, and the minimal estimated frequency of heterozygotes ranges from 141 to 1:154 in northeastern Quebec (Moorjani et al, 1989). While six mutations in the LDL receptor gene are responsible for 85% of French Canadian (FC) heterozygous FH patients, defined on the basis of clinical and biochemical criteria (Simard et al, 1994), 15% of suspected cases are still uncharacterized at the molecular level. Two of those mutations, a > 15-kb deletion at the 5' end of the gene and a missense mutation (W66G) in exon 3, are present in approximately 60% and 18% of FH patients who attend our lipid clinic in Quebec city, respectively.…”