False-negative factor V Leiden genetic testing in a patient with recurrent deep venous thrombosis

False-negative genetic testing of the factor V Leiden (fVL) mutation is unusual. We report a case of a young woman with a history of deep venous thrombosis tested for the fVL at four separate laboratories on four separate dates. Two laboratories reported the patient to be heterozygous for the fVL, while the other two reported no evidence of a mutation. Testing methods of the various laboratories were reviewed, and additional testing was performed on stored and newly drawn DNA samples, including sequencing of the fVL gene segment. The preponderance of evidence indicates the patient to be heterozygous for the fVL mutation. Dissection of data suggests that either sample misidentification or faulty allele specific amplification methods could have led to false-negative results in two laboratories. In one of the two laboratories, misinterpretation of results and clerical error could not be excluded. There is a need for standardization of optimized fVL genetic testing methods. Further education of ordering physicians on the limitations of genetic testing is necessary.