title: Type II antithrombin deficiency caused by a founder mutation Pro73Leu in the Finnish population: clinical picture.
abstract: BACKGROUND
  It has been shown that some antithrombin (AT) activity assays do not correctly detect inherited type II AT deficiency, but erroneously classify these patients as normal.
  
  
  OBJECTIVE
  Our aim was to investigate the mutations causing type II AT deficiency and to correlate the AT activity results with the genetic findings.
  
  
  METHODS
  A large population (n = 104; 42 families) of Finnish patients with known AT type II deficiency were interviewed for clinical data. Their AT activity was measured with five commercially available methods, and the SERPINC1 gene was genotyped.
  
  
  RESULTS
  The mutations detected in type II AT-deficient patients were as follows: p.Pro73Leu (AT Basel) in 37 of 42 (88.1%) families; and p.Val30Glu, p.Arg425Cys and p.Pro439Ala in one family each. In two families, no mutation was detected. In the carriers of AT Basel two AT activity assays correctly identified most of the patients as AT-deficient, whereas three assays misclassified almost all of these patients as normal. Carriers of the founder mutation had, in addition to an elevated risk of venous thrombosis, a high risk of arterial thrombosis at young age, especially stroke.
  
  
  CONCLUSIONS
  In Finland, a population with a strong founder effect, AT type II deficiency is caused predominantly by a single point mutation, p.Pro73Leu. The mutation is associated with a significant thrombotic risk. Reduced AT activity caused by this mutation cannot be detected by all available screening methods. This must be taken into account in the choice of laboratory method used for screening.
authors.affiliation: Hemostasis Laboratory, Finnish Red Cross Blood Service, Helsinki, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Puurunen
authors.forename: P
authors.initials: P
authors.lastname: Salo
authors.forename: S
authors.initials: S
authors.lastname: Engelbarth
authors.forename: K
authors.initials: K
authors.lastname: Javela
authors.forename: M
authors.initials: M
authors.lastname: Perola
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000991:Antithrombins / Q000378:metabolism*; D001483:Base Sequence; D015331:Cohort Studies; D017931:DNA Primers; D005260:Female; D005387:Finland; D018703:Founder Effect; D006801:Humans; D007930:Leucine / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011392:Proline / Q000235:genetics*; D055815:Young Adult
chemical_list: D000991:Antithrombins; D017931:DNA Primers; D011392:Proline; D007930:Leucine
keywords: antithrombin III deficiency; pregnancy complications; stroke; thrombophilia; venous thrombosis