Optimizing a cystic fibrosis test for the U.S. population

Abstract

Objective: To develop a practical diagnostic test for cystic fibrosis (CF) that provides maximal information to a diverse testing population, which includes multiple ethnic groups as well as individuals with a broad range of clinical indications or CF phenotypes.Methods: A molecular assay was developed to test for 70 CF mutations selected from more than 600 previously reported mutations. We tested more than 35,000 individuals for 70 CF mutations. To perform the assay, samples were amplified in two multiplex reactions, immobilized on a solid support, and hybridized with pools of allele-specific oligonucleotide probes. Positive samples were further analyzed by hybridization with individual allele-specific oligonucleotides.Results: We tested over 35,000 individuals for 70 CF mutations. Detection data will be presented for each mutation with respect to indications for testing and ethnic origins. Based on these data, we reevaluated the 70 mutation testing panel and developed an 86 mutation panel more appropriate to the test population. Seven mutations not detected were eliminated, and 23 new mutations were added to improve detection rates in specific groups.Conclusions: A CF mutation panel appropriate to the U.S. test population was optimized. The panel is useful for diagnostic testing—for CF, for infertility with congenital absence of the vas deferens, and for follow-up of abnormal fetal ultrasound examination; or for carrier screening—for individuals with a family history, pregnant couples, couples planning pregnancy, and gamete donors.