High heterogeneity of CFTR mutations and unexpected low incidence of cystic fibrosis in the Mediterranean France

Abstract

In this report, we present updated spectrum and frequency of mutations of the CFTR gene that are responsible for cystic fibrosis (CF) in Languedoc-Roussillon (L-R), the southwestern part of France. A total of 75 different mutations were identified by DGGE in 215 families, accounting for 97.6% of CF genes and generating 88 different mutational genotypes. The frequency of p.F508del was 60.23% in L-R versus 67.18% in the whole country and only five other mutations (p.G542X, p.N1303K, p.R334W, c.1717-1G>A, c.711+1G>T) had a frequency higher than 1%. The mutations were scattered over 20 exons or their border. This sample representing only 5.7% of French CF patients contributed to 24% of CFTR mutations reported in France. This is one of the highest molecular allelic heterogeneity reported so far in CF. We also present the result of a neonatal screening program based on a two-tiered approach "IRT/20 mutations/IRT" analysis on blood spots, implemented in France with the aim to improve survival and quality of life of patients diagnosed before clinical onset. This 18-month pilot project showed an unexpected low incidence of CF (1/8885) in South of France, with only six CF children detected among 43,489 neonates born in L-R, and 13 among 125,339 neonates born in Provence-Alpes-Côte-d'Azur (PACA).

Analysis of the CFTR gene in Iranian cystic fibrosis patients: Identification of eight novel mutations

“…The geographical distribution of the p.F508del shows a decreasing frequency from the Northwest to the Southeast of Europe [13,24,29,31,33,34]. The Islamic Republic of Iran is located to the Southeast of Turkey, and based on this gradient, the observed lower frequency of the p.F508del is in agreement with this observation.…”

CFTR allelic heterogeneity in Brazil: historical and geographical perspectives and implications for screening and counseling for cystic fibrosis in this country

“…8 In heterogeneous populations, the number of different mutations is very large. [9][10][11][12] A worldwide survey found that 28 493 of the 43 077 studied CF chromosomes (66%) carried the p.F508del mutation. 13 The frequency of the p.F508del mutation differs between populations, ranging from 26% in Algeria and Venezuela to 47% in one Brazilian study and 87% in Denmark; other mutations also vary widely depending on the ethnic composition of the studied groups.…”

Preliminary study of haplotypes linked to the rare cystic fibrosis E1104X mutation

“…The E1104X mutation was later described in Germany by Reiss in 1993 (21), in France (4,23,24), and in US (10).…”