DETECTION OF 5 NOVEL MUTATIONS OF THE CYSTIC-FIBROSIS TRANSMEMBRANE REGULATOR (CFTR) GENE IN PAKISTANI PATIENTS WITH CYSTIC-FIBROSIS - Y569D, Q98X, 296-GREATER-THAN-C), 1161DELC AND 621+2(T-GREATER-THAN-C)(12(T)

We analysed DNA samples from 26 Pakistani patients with cystic fibrosi s (CF) living in the United Kingdom (14 from patients residing in the north west of England, who were referred directly to the North West Re gional Molecular Genetics Laboratory, and 12 from other regional molec ular genetics laboratories). Of 56 mutations seen in native U.K. CF pa tients, only DeltaF508, R709X, and 2184insA were detected in the Pakis tani patients, Combined SSCP/Heteroduplex analysis, DGGE, and direct D NA cycle sequencing revealed five navel mutations: Y569D), Q98X, 296+1 2(T>C), 2261delC, and 621+2(T>C), which appear to be specific to Pakis tani CF families, In addition, a novel polymorphism, 297-67(A/C), and three previously described rare mutations, 1525-1(G>A), R560S, and 189 8+1(G>T), were detected. In the 14 Pakistani CF patients from the nort h west of England, DeltaF508 accounted for similar to 32% (9/28 chromo somes) and the overall detection rate of CF mutations in this group wa s similar to 86% (24/28 chromosomes). (C) 1998 Wiley-Liss, Inc.