title: Single founder mutation (W380G) in type II protein C deficiency in Finland.
abstract: The present study investigated the genetic basis for type II protein C deficiency in Finland, where this form has an unusually high incidence. We demonstrated 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 chromosomal conservation, i.e. a specific haplotype, around the W380G mutation was indicated in unrelated patients. Third, a local geographical origin for the W380G mutation was suggested by genealogical data. These results are in contrast to the heterogeneity in type II protein C deficiency elsewhere, but closely parallel disorders of the Finnish disease heritage. The high frequency of the type II disease can be explained by founder effect and subsequent enrichment of a single mutation in Finland. The present study also provided a simple means for genetic diagnosis of this disease and the genetic test can be included in the routine screenings in this population.
authors.affiliation: Finnish Red Cross Blood Transfusion Service, Helsinki.
authors.forename: A
authors.initials: A
authors.lastname: Levo
authors.forename: K
authors.initials: K
authors.lastname: Kuismanen
authors.forename: P
authors.initials: P
authors.lastname: Holopainen
authors.forename: E
authors.initials: E
authors.lastname: Vahtera
authors.forename: V
authors.initials: V
authors.lastname: Rasi
authors.forename: P
authors.initials: P
authors.lastname: Holopainen
authors.forename: V
authors.initials: V
authors.lastname: Rasi
authors.forename: T
authors.initials: T
authors.lastname: Krusius
authors.forename: J
authors.initials: J
authors.lastname: Partanen
mesh_terms: D002874:Chromosome Mapping; D017124:Conserved Sequence; D005192:Family Health; D005387:Finland / Q000453:epidemiology; D018703:Founder Effect; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D017354:Point Mutation; D020151:Protein C Deficiency / Q000145:classification / Q000235:genetics*; D019371:Topography, Medical