Identification of the I507 deletion by site-directed mutagenesis

We describe a compound heterozygous delta-F508/delta-I507 cystic fibrosis patient. Molecular analysis by polymerase chain reaction (PCR)-mediated site-directed mutagenesis showed the 219 bp fragment observed in delta-F508 homozygotes. The father showed a delta-F508 heterozygous pattern while the mother and sister showed a normal pattern. There were four possibilities to explain these results: a) the patient was a delta-F508/delta-I507 compound heterozygote, because the delta-I507 allele fails to amplify when analyzed with delta-F508 primers due to a double mismatch between the primers and template; b) uniparental isodisomy; c) nonmaternity; and d) sample processing mix-up. We then tested for the delta-I507 mutation using specific primers with a single base mismatch, and we found that the patient was in fact a compound heterozygote who inherited the delta-F508 mutation from the father and the delta-I507 from the mother. We underscore the need to detect this rare deletion in patients showing a delta-F508 homozygous pattern when one parent, particularly the father, is a noncarrier.