WS8.1 The first 1,000 CFTR genes sequenced in the Mayo Clinic Clinical Molecular Genetics Laboratory

Introduction: The Mayo Clinic Molecular Genetics Laboratory has completed whole CFTR gene analysis for 1,154 clinical samples. Here we report our findings for a large set of samples analyzed in an academic reference laboratory setting. Methods: All exons of the CFTR gene were sequenced using an automated, laboratory developed fluorescent Sanger sequencing workflow. Whole exon deletion/duplication testing was done using MLPA (MRC Holland). Results: 43% of samples were positive for the detection of at least one potentially disease causing allele (including 5T). 140 individuals had 2 known mutations detected, 271 were carriers of one known mutation; 57 had one mutation and one variant of uncertain significance (VUS), 100 had one VUS, and 17 had 2 or more VUS’s. Of the cases with 2 mutations, 25 had one copy of the 5T allele (13 dF508/5T); and, 41 had 2 copies of ACMG mutations (16 homozygous dF508). Homozygous results were seen for 6 additional mutations: 2954delT, G27X, I1234V, S945L, R75X, and R117H-7T in a 30 y/o female with pancreatitis. The majority of cases (125/140) with 2 known, disease causing mutations were seen in patients whose samples had a reason of referral (RFR) of possible or definite CF (or Unknown RFR) versus those with RFR’s for pancreatitis (9) or male infertility (6). Conclusions: The high positivity rate indicates that the test is being ordered appropriately. However, the high number of cases with 2 ACMG panel mutations indicates that testing first with a panel test may be more cost effective. The number of VUS’s is higher in individuals over 21 y/o and with a reason of referral of pancreatitis that in individuals being tested at under 21 years of age.