DETECTION OF 100-PERCENT OF THE CFTR MUTATIONS IN 63 CF FAMILIES FROMTYROL

We identified 100% of the CFTR gene mutations, including three novel m utations, in 126 unrelated cystic fibrosis chromosomes from Tyrol, Aus tria. The frequency of the major mutation Delta F508 (74.6%) was not s ignificantly different in Tyrolian CF-patients than in patients from B avaria (71.0%) and Middle- and Northern Germany (71.9%), but was signi ficantly higher than in patients from Styria (58.1%) or Northern Italy (47.6%). interestingly, the distribution of the next most frequent mu tations, R1162X (8.7%) 2183AA --> G, 2789 + 5G --> A and G542X (2.4% e ach), was more similar to the distribution of these mutations among CF -patients from Northern Italy than to those from Styria, Bavaria or Mi ddle- and Northern Germany. Nine further mutations occurred once or tw ice. One of these, the missense mutation M1101K, is rare worldwide but very frequent in the Hutterite brethren, a small founder population w hich came from Southern Austria to Northern America. Three other diffe rent mutations (Delta L453, 1874insT and 4108delT) were present in sin gle Tyrolian families and have not been described before. The identifi cation of 100% of CFTR gene mutations in a particular CF population de monstrates the power of genetic analysis for the diagnosis and counsel ling of CF families in this restricted geographical area of Austria. O ur study provides evidence for a closer genetic relation between CF pa tients from Tyrol and those from Bavaria or Middle- and Northern Germa ny as well as Northern Italy, than between CF patients from the two Au strian states Tyrol and Styria.