1. Spectrum of CFTR mutations in cystic fibrosis and in congenital absence of the vas deferens in France
- Author
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Francoise Chevalier, C. Verlingue, Isabelle Creveaux, Thierry Bienvenu, Jean-Claude Chomel, Eric Bieth, M.-C. Malinge, Michèle Chery, Perrine Malzac, Albert Iron, Mireille Claustres, C. Guittard, Emanuelle Girodon, Christine Clavel, Nicole Monnier, Claude Férec, Jean-Paul Bonnefont, Martine Blayau, Hervé Mittre, Cécile Cazeneuve, Delphine Feldmann, Viviane Dumur, Marie des Georges, Guy Lalau, and Dominique Bozon
- Subjects
Adult ,Male ,medicine.medical_specialty ,Cystic Fibrosis ,Genotype ,Mutation, Missense ,Cystic Fibrosis Transmembrane Conductance Regulator ,Biology ,medicine.disease_cause ,Gastroenterology ,Cystic fibrosis ,Vas Deferens ,Gene Frequency ,Internal medicine ,Genetics ,medicine ,Humans ,Allele ,Frameshift Mutation ,Gene ,Alleles ,Infertility, Male ,Genetics (clinical) ,Mutation ,Polymorphism, Genetic ,Vas deferens ,Middle Aged ,medicine.disease ,Congenital absence of the vas deferens ,Mutagenesis, Insertional ,medicine.anatomical_structure ,Mutation testing ,France ,Chromosome Deletion - Abstract
We have collated the results of cystic fibrosis (CF) mutation analysis conducted in 19 laboratories in France. We have analyzed 7, 420 CF alleles, demonstrating a total of 310 different mutations including 24 not reported previously, accounting for 93.56% of CF genes. The most common were F508del (67.18%; range 61-80), G542X (2.86%; range 1-6.7%), N1303K (2.10%; range 0.75-4.6%), and 1717-1G>A (1.31%; range 0-2.8%). Only 11 mutations had relative frequencies >0. 4%, 140 mutations were found on a small number of CF alleles (from 29 to two), and 154 were unique. These data show a clear geographical and/or ethnic variation in the distribution of the most common CF mutations. This spectrum of CF mutations, the largest ever reported in one country, has generated 481 different genotypes. We also investigated a cohort of 800 French men with congenital bilateral absence of the vas deferens (CBAVD) and identified a total of 137 different CFTR mutations. Screening for the most common CF defects in addition to assessment for IVS8-5T allowed us to detect two mutations in 47.63% and one in 24.63% of CBAVD patients. In a subset of 327 CBAVD men who were more extensively investigated through the scanning of coding/flanking sequences, 516 of 654 (78. 90%) alleles were identified, with 15.90% and 70.95% of patients carrying one or two mutations, respectively, and only 13.15% without any detectable CFTR abnormality. The distribution of genotypes, classified according to the expected effect of their mutations on CFTR protein, clearly differed between both populations. CF patients had two severe mutations (87.77%) or one severe and one mild/variable mutation (11.33%), whereas CBAVD men had either a severe and a mild/variable (87.89%) or two mild/variable (11.57%) mutations.
- Published
- 2000