Testing and reporting ACMG cystic fibrosis mutation panel results

Abstract

Testing strategies and summary reports for pregnant patients and symptomatic patients being tested for cystic fibrosis (CF; MIM 219700) were developed based upon calculated after (posterior) test risk tables incorporating patient and family histories, ethnicities, and prior testing status. This manuscript defines the proportion of all mutations detected by the American College of Medical Genetics (ACMG)-recommended 23-mutation cystic fibrosis transmembrane conductance regulator (CFTR) gene core panel when testing all patient categories with severe symptoms, including pregnant couples with no family history as well as CF patients, their partners, and other family members. Reference tables incorporate prior and posterior test risks sufficient to complete >99% of all tested cases and to report the results according to HIPAA guidelines. These tables were calculated based on the assumption that all patient samples have been collected, labeled, analyzed, and reported correctly, including the patient's reported relationship to a known affected or carrier relative, even though the template letter states that the likelihood is about 99% that each reported result is accurate. Pedigrees and tables with the prior (before; a priori) test risks of patients offered CF screening with a family history of a CF patient and/or a known carrier patient are provided for ready reference with each risk frequency, dependent upon the assumption that the patient's pedigree reflects familial relationships correctly. Comparison of tables emphasizes the value of asking the tested partner to ask a relative known to have CF or who tested positive for a CF mutation to donate a sample as a DNA test control and/or to obtain a copy of a prior molecular test result and/or extracted DNA sample. These tables posterior test risks also indicate that when one partner with no family history tests negative for the 23 mutation panel, no further prenatal testing is indicated.