High heterogeneity of CFTR mutations and unexpected low incidence of cystic fibrosis in the Mediterranean France.
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).
des Georges
Marie
M
Laboratoire de Génétique Moléculaire, CHU de Montpellier, Institut Universitaire de Recherche Clinique (IURC), 641 avenue du Doyen Gaston Giraud, 34093 Montpellier Cedex 5, France.
Guittard
Caroline
C
Altiéri
Jean-Pierre
JP
Templin
Carine
C
Sarles
Jacques
J
Sarda
Pierre
P
Claustres
Mireille
M
D000328:Adult; D000368:Aged; D000483:Alleles; D003550:Cystic Fibrosis / Q000453:epidemiology* / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004200:Diseases in Twins; D005260:Female; D005602:France / Q000453:epidemiology; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D019083:Mediterranean Region / Q000453:epidemiology; D009154:Mutation; D020125:Mutation, Missense / Q000235:genetics; D010865:Pilot Projects; D012189:Retrospective Studies; D012307:Risk Factors
C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator