Results of Genetic Testing in 855 Consecutive Unrelated Patients Referred for Long QT Syndrome in a Clinical Laboratory.

Lieve KV, Williams L, Daly A, Richard G, Bale S, Macaya D, Chung WK.

Source

1 Department of Pediatrics, Columbia University , New York, New York.

Abstract

Aim: Our aim was to examine the diagnostic yield of genetic testing in 855 consecutive unrelated cases referred for Long QT syndrome (LQTS). Results: Eight hundred fifty five consecutive patients with a mean age at testing of 27.5±18.6 years, were referred for LQTS genetic testing and had accompanying clinical information. KCNQ1, KCNH2, SCN5A, ANK2, KCNE1, KCNE2, CACNA1C, KCNJ2, CAV3, and SCN4B were analyzed using Next-Generation sequencing in all patients, and 395 patients were also tested for an additional two genes, AKAP9 and SNTA1. We retrospectively analyzed the diagnostic yield of this genetic test and factors that predicted the likelihood of a disease causing mutation using ANOVA, χ2, t-test, and receiver operator curves. At least one mutation was identified in 30.3% of the patients (n=259), and 18 patients (2.1%) had two mutations. Patients with two mutations had a longer QTc interval (p<0 .01="" 476="" 49="" 72="" a="" and="" arrest="" associated="" cardiac="" clinical="" conclusion:="" cutoff="" domain="" domains="" duration="" each="" family="" for="" frequency="" gene.="" genetic="" greater="" had="" has="" higher="" history="" in="" kcnq1="" longer="" lqts="" msec="" mutation.="" mutations="" of="" on="" one="" or="" other="" p="" patients="" positive="" qtc="" relative="" results="" risk="" scn5a="" sensitivity="" sequencing-based="" specificity="" syncope="" testing="" than="" the="" to="" transmembrane="" using="" utility.="" were="" with="" within="" yield="">