ObjectiveTo document the results of mutation analysis on 160 individuals with cystic fibrosis and 31 obligate carriers of the cystic fibrosis gene in 191 Western Australian families to facilitate accurate genetic counselling. MethodsWe tested for 17 mutations of the cystic fibrosis gene by either a variation of the polymerase chain reaction amplification refractory mutation system (PCR‐ARMS) or with a series of restriction enzyme cuts and dot blots using chemiluminescent probes. ResultsAt least one of the two intragenic mutations causing cystic fibrosis was identified in 98% of affected individuals and both were detected in 68%. The AF508 deletion occurred in 89.8% of patients: 51% were homozygous for this defect. In carriers, 85% of the mutations were detected with a panel of 16 probes, identifying 17 intragenic defects: the AF508 deletion occurred in 72.4%. Both cystic fibrosis mutations were detected in 68% of cystic fibrosis families. ConclusionsBy analysis with 16 intragenic cystic fibrosis genomic probes, we have documented the frequencies of various mutations in the Western Australian population. These data will be useful in accurate genetic counselling for affected families and carrier screening for the general population.

Objective: To assess the provision of accurate pre‐symptomatic genetic testing with DNA analysis and appropriate counselling for individuals and families known to be at high risk of developing familial adenomatous polyposis coli (FAP). Patients and methods: Thirty‐one families with clinically and pathologically documented FAP were ascertained from the Western Australian Polyposis Registry. DNA was collected from over 200 individuals in these families to establish their genetic risk status for FAP, either by direct mutation analysis, or by linkage analysis. Individuals undergoing DNA testing were given intensive psychosocial support and counselling. Results: In 19 families DNA‐based counselling could not be offered because either the adenomatous polyposis coli (APC) gene mutation could not be detected or there were insufficient family members for linkage analysis. Gene testing yielded mutations of the APC gene in 87 individuals from 12 families; by gene tracking (or linkage analysis) in three families and by mutation analysis in the remaining nine (four of which had only one affected individual). DNA results conformed with a definite clinicopathological diagnosis in 27 FAP patients and, of the remaining 60 high‐risk subjects tested, 14 had inherited the mutated APC gene. Conclusions: DNA analysis allowed accurate genetic counselling for 12 of 31 families affected by FAP, thus improving the medical and personal management in asymptomatic people who would otherwise be subjected to the uncertainty of long term surveillance and repeated colonic examinations. In future a superior biomolecular approach to gene mutation analysis, such as the protein truncation test, will facilitate management for most FAP individuals and families.

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