IDENTIFICATION OF 8 MUTATIONS AND 3 SEQUENCE VARIATIONS IN THE CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR (CFTR) GENE

To determine cystic fibrosis (CF) defects in a sample of 224 non-Delta F508 CF chromosomes, we used denaturing gradient gel multiplex analysis of CF transmembrane conductance regulator gene segments, a strategy based on blind exhaustive analysis rather than a search for known mutations. This process allowed us to detect 11 novel variations comprising two nonsense mutations (Q890X and W1204X), a splice defect (405 + 4 A --> G), a frameshift (3293delA), four presumed missense mutations (S912L, H949Y, L1065P, Q1071P), and three sequence polymorphisms (R31C or 223 C/T, 3471 T/C, and T1220I or 3791 C/T). We describe these variations, together with the associated phenotype when defects on both CF chromosomes were identified. (C) 1994 Academic Press, Inc.