Expression and intracellular processing of chimeric and mutant CFTR molecules.

The cystic fibrosis transmembrane conductance regulator (CFTR) is a cyclic AMP-activated chloride channel comprising two membrane-spanning domains (MSDs), two nucleotide-binding domains (NBDs) and a unique regulatory (R) domain. The most frequent cystic fibrosis (CF) mutation, a deletion of Phe508 in NBD1, results in the retention of the DeltaF508 CFTR in the endoplasmic reticulum, as do many other natural or constructed mutations located within the first NBD. In order to further define the role of NBD1 in CFTR folding and to determine whether the higher frequency of mutations in NBD1 with respect to NBD2 results from its position in the molecule or is related to its primary sequence, we constructed and expressed chimeric CFTRs wherein NBD domains were either exchanged or deleted.

Prevalence of the delta F508 deletion of the cystic fibrosis gene in Belgian patients.

A sample of 107 Belgian cystic fibrosis patients has been tested for the presence of the delta F508 deletion. We have shown that 166 (78%) of the CF chromosomes presented the deletion, and that 97% of the deleted chromosomes and 50% of the non-deleted chromosomes presented the haplotype B (KM19-2/XV2c-1).

Carrier prediction of cystic fibrosis in 36 families by means of restriction fragment length polymorphism.

Transmission of cystic fibrosis (CF) was studied in 36 families with at least one affected and one unaffected child. DNA was prepared from peripheral leukocytes and submitted to restriction fragment length polymorphism (RFLP) analysis with two CF probes (pj3.11 and met).