Molecular analysis of the cystic fibrosis gene reveals a high frequency ofthe intron 8 splice variant 5T in Egyptian males with congenital bilateralabsence of the vas deferens

It has previously been shown that defects in the cystic fibrosis transmembr ane conductance regulator (CFTR) gene are largely responsible for the condi tion of congenital bilateral absence of the vas deferens (CBAVD), without a ssociated renal abnormalities, in Caucasian populations. To assess the invo lvement of the CFTR in CBAVD in a population with presumed low cystic fibro sis (CF) frequency, we have analysed 20 CBAVD males from Egypt for the pres ence of 12 common Caucasian CFTR mutations and the intron 8 5T splice varia nt, IVS-5T, known to be a major cause of CBAVD in Caucasian patients. In 16 of the males without associated renal abnormalities only one Delta F508 ca rrier was identified, but an exceptionally high frequency of the IVS-5T var iant was found (14 of 32 alleles or 43.7%), confirming that this variant is involved in many cases of CBAVD, even in populations where CF is rare. CFT R mutations or the IVS-5T variant were found neither in the remaining four patients with associated renal abnormalities nor in the spouses of the 20 C BAVD patients. However, one patient was homozygous for a leucine to proline substitution at amino acid position 541 (L541P) of the CFTR. It is as yet not clear whether this change is involved in CBAVD in this male.