Cystic fibrosis (CF) (MIM 219700) is one of the most common autosomal recessive diseases in Caucasians.¹ It affects about 1 in 2500 births and approximately 1 in 25 individuals are heterozygotes, with marked regional variations² (www.genet.sickkids.on.ca/cftr). It is caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR or ABCC7) gene (MIM 602421), which is also involved in a broad spectrum of phenotypes, including male infertility by congenital bilateral absence of the vas deferens (CBAVD),^3–5 disseminated bronchiectasis (DB),^6,7 and chronic pancreatitis.^8,9 So far, over 1000 CFTR gene mutations have been described throughout the gene, along with geographic and ethnic variations in their distribution and frequency (www.genet.sickkids.on.ca/cftr).^2,10 Of these variations, 99% consist of point mutations or micro-deletions/insertions (www.genet.sickkids.on.ca/cftr) but account for 33–98% of CF alleles, depending on the population.¹⁰ A number of cases remain unsolved after extensive and laborious screening of the 27 exons, thus making genetic counselling difficult for the patients and their families, particularly when the CF diagnosis is not certain. Unidentified CF mutations may lie in introns or in regulatory regions which are not routinely investigated, or correspond to gene rearrangements such as large deletions at the heterozygous state which escape detection using current PCR based techniques. Deletions have been suspected in a very few situations: upon failure of PCR amplification to target particular exons when the deletions were present in CF patients in the homozygous state, or in cases of abnormal segregation of a mutation or polymorphisms in a family. Two such deletions, CFTRdele2–3¹¹ and CFTRdele17a–18,¹² which are now routinely tested for by conventional PCR using specific primers, were found in about 5% and 13% of CF chromosomes in Slav and Arab populations, respectively.

Screening for unknown CFTR deletions still …