title: 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).
authors.affiliation: Laboratoire de Génétique Moléculaire, CHU de Montpellier, Institut Universitaire de Recherche Clinique (IURC), 641 avenue du Doyen Gaston Giraud, 34093 Montpellier Cedex 5, France.
authors.forename: Marie
authors.initials: M
authors.lastname: des Georges
authors.forename: Caroline
authors.initials: C
authors.lastname: Guittard
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Altiéri
authors.forename: Carine
authors.initials: C
authors.lastname: Templin
authors.forename: Jacques
authors.initials: J
authors.lastname: Sarles
authors.forename: Pierre
authors.initials: P
authors.lastname: Sarda
authors.forename: Mireille
authors.initials: M
authors.lastname: Claustres
mesh_terms: 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
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator