Cystic fibrosis mutations in French Canadians: Three CFTR mutations are relatively frequent in a Quebec population with an elevated incidence of cystic fibrosis

Abstract

The French-Canadian population in the Saguenay-Lac St. Jean region of northeastern Quebec has an elevated frequency of cystic fibrosis (CF). The average incidence of cystic fibrosis was 1 in 891 births and the prevalence of CF carriers was estimated to be 1 in 15. We tested for 10 mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene in 133 French-Canadian CF families from Quebec. Ninety-one families were from the Saguenay-Lac St. Jean region and 42 families were referred from other regions of Quebec. We detected the CFTR mutation in 93 and 92% of the CF chromosomes in the Saguenay-Lac St. Jean and the major-urban Quebec families, respectively. The two groups of French-Canadian families were significantly different for the proportions of CFTR mutations. The three most common mutations in the Saguenay-Lac St. Jean families were delta F508 (58%), 621 + 1G----T (23%), and A455E (8%); and in the major-urban Quebec families were delta F508 (71%), 711 + 1G----T (9%), and 621 + 1G----T (5%). These results provide evidence for the role of founder effect in the elevated incidence of cystic fibrosis in the Saguenay-Lac St. Jean population.

Improved detection of cystic fibrosis mutations in the heterogeneous U.S. population using an expanded, pan-ethnic mutation panel

“…Several mutations previously identified in other geographical regions were unexpectedly identified in Hispanics. Examples include 711 ϩ 1GϾT (frequency of 6.9% in Tunisia 5 and 9% in Quebec 19 ), 1677delTA (originally described in a small Georgian ethnic group in the U.S.S.R. 20 ), and Y1092X (originally identified in the Canadian population 21 and in the homozygous state in a CF patient of Jewish Egyptian origin 3 ).…”

Haplotype identity between individuals who share a CFTR mutation allele "identical by descent": demonstration of the usefulness of the haplotype-sharing concept for gene mapping in real populations

“…In Canada, this mutation was introduced by French immigrants during the period 1650-1900 (Rozen et al 1990(Rozen et al , 1992. The Dutch patients with an A455E mutation all come from southern parts of The Netherlands (unpublished results).…”

“…According to data from the CF consortium (Cystic Fibrosis Genetic Analysis Consortium 1994), this mutation is mainly detected among French Canadian and Dutch CF patients. The A455E mutation comprises 8% of all CF mutations in the French Canadian population of the Saguenay-Lac St. Jean region of Quebec (Rozen et al 1992) and 3% in The Netherlands (unpublished data). The overall CF carrier frequency is 1 in 15 in this particular French Canadian population (Rozen et al 1992) and 1 in 30 in The Netherlands (ten Kate 1977).…”

“…The A455E mutation comprises 8% of all CF mutations in the French Canadian population of the Saguenay-Lac St. Jean region of Quebec (Rozen et al 1992) and 3% in The Netherlands (unpublished data). The overall CF carrier frequency is 1 in 15 in this particular French Canadian population (Rozen et al 1992) and 1 in 30 in The Netherlands (ten Kate 1977). This results in allele frequencies of 1/400 (8% of 1/30) and 1/2000 (3% of 1/60), respectively.…”

Report on the p.Ser489X (p.Ser489*) CFTR mutation, a variant with severe associated phenotype and high prevalence in a Quebec French-Canadian cystic fibrosis patient population

“…In this population, three Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations account for ~94% of disease alleles, namely p.Phe508del (p.F508del; [delta] F508, c.1521_1523delCTT), 621+1G>T (c.489+1G>T), and p.Ala455Glu (p.A455E; c.1364C>A). 3,4 Molecular CFTR testing is usually performed to confirm a clinical diagnosis of CF, to determine carrier status in individuals at risk, or to corroborate results of newborn screening. To date, nearly 2,000 mutations have been identified within the CFTR gene (Cystic Fibrosis Mutation Database: http://www.genet.sickkids.on.ca/Home.html).…”