GeneDx is the first laboratory to offer testing for deletions/duplications in 10 genes associated with Long QT Syndrome (LQTS). It has been shown that approximately 10% of patients with LQTS who test negative for a mutation by DNA sequencing will have a deletion/duplication that involves one of the LQTS genes (Eddy et al. Heart Rhythm 5:1275-1281, 2008). As such deletions/duplications cannot be detected by either NextGeneration or capillary (Sanger) sequencing, GeneDx has developed a high-resolution oligonucleotide microarray for comparative genomic hybridization (array CGH) with probes concentrated in the exons of 10 LQTS genes. This new assay (‘LQTS ExonArrayDx’) is specifically designed to detect both whole-gene deletions/duplications and small deletions/duplications of one or more exons, in any of the 10 LQTS genes: KCNQ1, KCNH2, SCN5A, ANK2, KVNE1, KCNE2, CACNA1C, KCNJ2 and CAV3. Each positive finding is confirmed using another quantitative detection method.
Microarray-based LQTS deletion/duplication analysis is expected to increase the sensitivity of molecular diagnostic testing in LQTS and is recommended as a reflex test if sequencing does not to identify a disease-causing mutation.