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Type II antithrombin deficiency caused by a founder mutation Pro73Leu in the Finnish population: clinical picture
- Source :
- Journal of thrombosis and haemostasis : JTH. 11(10)
- Publication Year :
- 2013
-
Abstract
- Summary 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. Objectives Our aim was to investigate the mutations causing type II AT deficiency and to correlate the AT activity results with the genetic findings. Patients/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. Conclusion 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.
- Subjects :
- Adult
Male
medicine.medical_specialty
Proline
Population
Thrombophilia
Antithrombins
Cohort Studies
Young Adult
Leucine
Internal medicine
Medicine
Humans
education
Finland
Aged
DNA Primers
Genetics
Aged, 80 and over
education.field_of_study
Base Sequence
business.industry
Point mutation
Antithrombin
Antithrombin III deficiency
Hematology
Middle Aged
medicine.disease
Founder Effect
Venous thrombosis
Mutation (genetic algorithm)
Mutation
Female
business
Founder effect
medicine.drug
Subjects
Details
- ISSN :
- 15387836
- Volume :
- 11
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Journal of thrombosis and haemostasis : JTH
- Accession number :
- edsair.doi.dedup.....8f854462000f881c19933e79a3a6a706