External quality assurance of DNA testing for thrombophilia mutations.

Because of the potential implications of results of genetic analyses of thrombophilic mutations, laboratories must undertake stringent internal quality control measures and participate in external quality assurance (QA) programs. A small number of external QA surveys of thrombophilic defects have been conducted across a large number of molecular laboratories and generally have indicated favorable levels of correct responses. The Royal College of Pathologists of Australasia QA program has conducted external QA testing of factor V Leiden G1691 A, prothrombin G20210A, and MTHFR C677T gene mutations for the past 5 years, including 133 DNA samples in 10 multilaboratory surveys. Of 3,799 responses, the overall success rate was 98.63%; the poorest individual sample result was 15% incorrect for a homozygous factor V Leiden sample. Success rates in identifying specific mutations were 98.13% for factor V Leiden, 98.84% for prothrombin G20210A, and 99.3% for the MTHFR C677T mutation. Among responding laboratories, 51% (20/39) made at least 1 error; 3 of 39 laboratories were responsible for 46% of all errors (24/52). Although encouraging, these data underscore the need for ongoing participation of molecular diagnostic laboratories in external QA programs to ensure the provision of quality genetic testing services.