(Download) "Ensuring Accurate Molecular Genetic Testing (Editorial)" by Clinical Chemistry # Book PDF Kindle ePub Free
eBook details
- Title: Ensuring Accurate Molecular Genetic Testing (Editorial)
- Author : Clinical Chemistry
- Release Date : January 01, 1998
- Genre: Chemistry,Books,Science & Nature,
- Pages : * pages
- Size : 159 KB
Description
In this issue of Clinical Chemistry, Lutz et al. (1) report on a multicenter evaluation of polymerase chain reaction (PCR) methods for the detection of Factor V Leiden genotypes. Mutations in the Factor V Leiden gene have been shown to result in activated protein C (APC) resistance, which is the most common cause of inherited venous thrombosis in Caucasians (2-4). In particular, a specific mutation in the Factor V Leiden gene, a guanine-to-adenine substitution at nucleotide 1651 that results in a glutamine-to-arginine substitution at position 506 (R506Q), has been shown to be associated with APC resistance (2, 3). Clinically, individuals who are heterozygous for this mutant allele have a 5- to 10-fold increased risk for thrombotic events, and individuals who are homozygous have a 50- to 100-fold increase (2,5). In the past, patients with APC resistance could be identified only by coagulation-based assays that are limited by decreased reliability of results in a number of conditions (e.g., pregnancy) and in patients receiving certain pharmacologic agents (e.g., anticoagulant therapy) (6). In contrast, molecular testing for the identification of Factor V Leiden gene mutation heterozygotes and homozygotes is not subject to these limitations. This advantage over coagulation-based assays has resulted in the rapid integration of this testing into clinical practice and its widespread availability. For example, in a recent survey of molecular genetic testing laboratory directors, Factor V Leiden mutation detection was available in 29% of 245 responding laboratories (7). In the study by Lutz et al., six laboratories that offer Factor V Leiden mutation analysis simultaneously tested a set of 62 blinded patient samples to determine the Factor V Leiden genotype. Although each of the participating laboratories had developed PCR-based assays, the exact testing system conditions varied substantially (e.g., PCR primer sequences, restriction endonucleases used). Thus, the purpose of the study was to compare the performance of the different assay systems by assessing whether the same genotype result was obtained for each patient specimen regardless of the methodology employed. In other words, Lutz et al. conducted an interlaboratory proficiency test (PT) for Factor V Leiden mutation detection. The results of the study by Lutz et al. revealed 100% concordance of results among the six laboratories, suggesting that the different methodologies used could each reliably identify the single base pair substitution. However, as with all PTs, these results must be examined carefully because a PT does not provide an assessment of the total testing process. Specifically, the preanalytical phase of testing (e.g., test requisition, accession, and sample preparation) is usually eliminated by the entry of the PT sample into the testing process at the analytical phase. Nevertheless, PT is an important indicator of laboratory performance and provides participating laboratories with the opportunity to identify areas in need of improvement and to develop plans for remedial action. Indeed, the Clinical Laboratory Improvement Amendments of 1988 (CLIA), which provide for regulation of all clinical laboratories, primarily rely on two performance indicators to evaluate laboratories: periodic on-site inspections and PT performance (8). The latter requirement is dependent on the complexity of the test being performed and the availability of an approved program.
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