Low-cost, rapid, and reliable screening for men1 mutations


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Crépin M _ et al_. (2006) Evaluation of denaturing high performance liquid chromatography for the mutational analysis of the _MEN1_ gene. _J Mol Endocrinol_ 36: 369–376 Currently, direct DNA


sequencing is the method of choice for detecting mutations in _MEN1_ (the gene associated with multiple endocrine neoplasia type 1). As no mutational hotspots exist in _MEN1_, the entire


gene must be sequenced, which is slow, labor intensive, and expensive. Denaturing high-performance liquid chromatography (DHPLC) is successfully used in the high-throughput, automated


detection of mutations in other tumor-associated genes, and researchers in France have now confirmed that DHPLC can detect _MEN1_ mutations with 100% sensitivity, equivalent to the


sensitivity of DNA sequencing. Crépin _ et al_. retrospectively analyzed 160 samples from unrelated patients with MEN1 for whom sequence data were available, as well as positive and negative


control samples. DHPLC results were obtained within a few hours. _MEN1_ mutations reveal characteristic patterns on DHPLC, which differ from those generated by wild-type DNA, but


confirmatory DNA sequencing is still required to identify specific mutations. Nonetheless, because DHPLC can reliably screen out samples containing only wild-type _MEN1_ and target


potentially mutated DNA fragments, the authors estimate the overall cost of _MEN1_ genotypic diagnosis using DHPLC to be fivefold cheaper than diagnosis based on complete DNA sequencing.


Neither DNA sequencing nor DHPLC can identify deletion or duplication of entire exons, however, detection of which requires quantitative analysis techniques. DHPLC is based on the detection


of DNA heteroduplexes formed in polymerase chain reaction products. The authors highlight that the specificity of DHPLC (98.6% in this study) depends on the purity of these products. RIGHTS


AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Low-cost, rapid, and reliable screening for _MEN1_ mutations. _Nat Rev Endocrinol_ 2, 362 (2006).


https://doi.org/10.1038/ncpendmet0207 Download citation * Issue Date: July 2006 * DOI: https://doi.org/10.1038/ncpendmet0207 SHARE THIS ARTICLE Anyone you share the following link with will


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