Spectrum of CFTR mutations in cystic fibrosis and in congenital absence ofthe vas deferens in France

We have collated the results of cystic fibrosis (CF) mutation analysis cond ucted in 19 laboratories in France. We have analyzed 7,420 CF alleles, demo nstrating a total of 310 different mutations including 24 not reported prev iously, 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 allele s (from 29 to two), and 154 were unique. These data show a clear geographic al and/or ethnic variation in the distribution of the most common CF mutati ons. This spectrum of CF mutations, the largest ever reported in one countr y, 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 s ubset of 327 CBAVD men who were more extensively investigated through the s canning of coding/flanking sequences, 516 of 654 (78.90%) alleles were iden tified, with 15.90% and 70.95% of patients carrying one or two mutations, r espectively, and only 13.15% without any detectable CFTR abnormality. The d istribution of genotypes, classified according to the expected effect of th eir mutations on CFTR protein, clearly differed between both populations. C F patients had two severe mutations (87.77%) or one severe and one mild/var iable mutation (11.33%), whereas CBAVD men had either a severe and a mild/v ariable (87.89%) or two mild/variable (11.57%) mutations. Hum Mutat 16:143- 156, 2000. (C) 2000 Wiley-Liss, Inc.