Single founder mutation (W380G) in type II protein C deficiency in Finland

The present study investigated the genetic basis for type II protein C defi ciency in Finland, where this form has an unusually high incidence. We demo nstrated that! first, a single novel mutation W380G in the protein C gene ( PROC) explained 25/26 index patients, estimated to represent two thirds of all families with type II deficiency in Finland. Second, extended chromosom al conservation, i.e. a specific haplotype, around the W380G mutation was i ndicated in unrelated patients. Third, a local geographical origin for the W380G mutation was suggested by genealogical data. These results are in con trast to the heterogeneity in type II protein C deficiency elsewhere, but c losely parallel disorders of the Finnish disease heritage. The high frequen cy of the type II disease can be explained by founder effect and subsequent enrichment of a single mutation in Finland. The present study also provide d a simple means for genetic diagnosis of this disease and the genetic test can be included in the routine screenings in this population.