A novel mutation in the CFTR gene correlates with severe clinical phenotype in seven Hispanic patients

The remaining 28 patients screened were from unrelated families. [...]this novel mutant allele represents a frequency of 10.3% (6/(29 x 2)) in this Hispanic patient group. Since ATP hydrolysis at NBD2 terminates a burst of activities associated with opening the channel, loss of NBD2 would confer a loss of the gating control. 21 A recent study shows that the Walker A motif in NBD2 is more solvent accessible than that in NBD1, suggesting a difference in structure and function for the two NBDs. 22 In addition to 3876delA, a few other mutations in NBD2, including G1244E, S1255P, S1255X, 3905insT, W1282X, N1303K, and G1349D, all result in a PI phenotype. 5 23 It should be noted that S1255P, S1255X, 3905insT, and 3876delA are all clustered around the Walker A motif.