MUTATION ANALYSIS OF WESTERN-AUSTRALIAN FAMILIES AFFECTED BY CYSTIC-FIBROSIS

Objective: To document the results of mutation analysis on 160 individ uals with cystic fibrosis and 31 obligate carriers of the cystic fibro sis gene in 191 Western Australian families to facilitate accurate gen etic counselling. Methods: We tested for 17 mutations of the cystic fi brosis gene by either a variation of the polymerase chain reaction amp lification refractory mutation system (PCR-ARMS) or with a series of r estriction enzyme cuts and dot blots using chemiluminescent probes. Re sults: At least one of the two intragenic mutations causing cystic fib rosis was identified in 98% of affected individuals and both were dete cted in 68%. The Delta F508 deletion occurred in 89.8% of patients: 51 % were homozygous for this defect. In carriers, 85% of the mutations w ere detected with a panel of 16 probes, identifying 17 intragenic defe cts: the Delta F508 deletion occurred in 72.4%. Both cystic fibrosis m utations were detected in 68% of cystic fibrosis families. Conclusions : By analysis with 16 intragenic cystic fibrosis genomic probes, we ha ve documented the frequencies of various mutations in the Western Aust ralian population. These data will be useful in accurate genetic couns elling for affected families and carrier screening for the general pop ulation.