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ARMS test for diagnosis of factor VLeiden mutation, a common cause of inherited thrombotic tendency

✍ Scribed by Chandri N. Yandava; David C. Zappulla; Bruce R. Korf; Ellis J. Neufeld


Publisher
John Wiley and Sons
Year
1996
Tongue
English
Weight
421 KB
Volume
10
Category
Article
ISSN
0887-8013

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✦ Synopsis


We developed a simple and rapid amplification-refractory mutation system (ARMS) assay for the factor V mutation [R506Q] (factor VLeiden), which reSUltS in the autosomal dominant thrombotic tendency, resistance to activated protein C (rAPC). PCR primers within Exon 10 of the factor V gene were designed. A common upstream primer was paired with either a mutant or wild-type-specific downstream primer. The 3'-rnost nucleotide of the specific primers recognized either the mutant or normal allele, and the 3' penultimate nucleotide was mismatched to enhance specificity of the reaction. The assay was validated using authentic factor V ~~i d ~~ DNA samples. Seven of 103 hematologically normal children (6.8%) were found to be het-erozygotes. Among 27 patients studied by the rAPC assay, ARMS assay and rAPC results were concordant in 26. Among these were a 1 -year-old child with a calcified clot in the inferior vena cava. Both the patient and his father were heterozygous for the mutation and both had abnormal rAPC assays. rAPC and factor VLeiden assays were discordant in a young girl with a history of stroke. Biochemical rAPC assay was abnormal, while ARMS assay revealed amplification only with wild-type primers, suggesting a non-[R506Q] mechanism for rAPC. This assay will be a valuable tool for studying subjects with thromboses and their family members. 0 1996 Why-Liss, Inc.