Journal of Interventional Cardiac Electrophysiology (2019) 56:171–172 https://doi.org/10.1007/s10840-019-00606-y CASE REPORTS Novel AKAP9 mutation and long QT syndrome in a patient with torsades des pointes Dario Bottigliero1 & Ilenia Monaco1 & Rosa Santacroce1 & Grazia Casavecchia1 & Michele Correale1 & Francesca Guastafierro1 & Angelica Leccese1 & Giorgia Cordisco1 & Riccardo Ieva2 & Roberta Trunzo1 & Matteo Di Biase3 & Maurizio Margaglione1 & Natale Daniele Brunetti1 Received: 22 March 2019 /Accepted: 2 August 2019 /Published online: 15 August 2019 # Springer Science+Business Media, LLC, part of Springer Nature 2019 We report the case of an 84-year-old man with hyper- DNA: heterozygosity for AKAP9 exon 9 (c.3673C>T tension, diabetes, dyslipidemia, paroxysmal atrial fibril- G>A, p.Leu1150Phe) and mutation (Fig. 1). The vari- lation, CABG, previous right nephrectomy, and post- ants have not been previously described in the literature surgical hypothyroidism, who was admitted to neurosur- and have not been previously reported in the Human gery for subdural hematoma after syncope. Admission Gene Mutation Database (HGMD); no other possible electrocardiogram showed sinus bradycardia with causative mutations were found. prolonged QT duration. Echocardiography showed left The in silico analysis performed using SIFT and PolyPhen ventricular hypertrophy with severe mitral regurgitation. modeling programs suggests that this new variant may be During hospitalization, several episodes of torsade de harmful. pointes (8 s longest duration), treated with medical ther- AKAP9 gene is a known modifier of LQTS clinical phe- apy (magnesium sulfate iv), occurred. ECG monitoring notype by altering QTc duration and influencing the risk of constantly showed long QT (QTC > 570–580 ms) while cardiac events and the severity of the disease. In particular, no evident cause of QT prolongation was found (e.g., variants that impair the function or expression of AKAP9- drugs); a dual-chamber ICD was therefore implanted. encoded Yotiao are prone to influence channel properties, Using next-generation sequencing (NGS) and subse- explaining the phenotypic differences described in literature quent mutation confirmation with traditional capillary [1, 2]. In this perspective, our case suggests possible associa- Sanger sequencing analysis, a possible causative non- tion between the novel mutation found and potential life- synonymous mutation was identified in the patient’s threatening complications. * Natale Daniele Brunetti Giorgia Cordisco [email protected] [email protected] Dario Bottigliero Riccardo Ieva [email protected] [email protected] Ilenia Monaco Roberta Trunzo [email protected] [email protected] Rosa Santacroce Matteo Di Biase [email protected] [email protected] Grazia Casavecchia Maurizio Margaglione [email protected] [email protected] Michele Correale [email protected] 1 Department of Medical & Surgical Sciences, University of Foggia, Foggia, Italy Francesca Guastafierro [email protected] 2 Cardiology Department, Ospedali Riuniti University Hospital, Foggia, Italy Angelica Leccese [email protected] 3 GVM Care & Research, Bari, Italy 172 J Interv Card Electrophysiol (2019) 56:171–172 Fig. 1 Left: sinus bradycardia and prolonged QT (640 ms). Right: AKAP9 exon 9 (c.3673C>T G>A, p.Leu1150Phe) mutation The patient was discharged 7 days after admission in ther- release channel, the L-type calcium channel, and the slowly apy with metoprolol 100 mg; 2-year follow-up was uneventful activating delayed rectifier IK potassium channel. and later electrocardiograms showed no significant differences. AKAP9 (A-kinase-anchoring protein) is a protein-coding gene, located in the long (q) arm of chromosome 7 at position References 21.2 (cytogenetic location: 7q21.2). The A-kinase-anchoring proteins (AKAPs) are a group of scaffolding proteins which 1. de Villiers CP, van der Merwe L, Crotti L, Goosen A, George AL Jr, have the common function of binding to the regulatory sub- Schwartz PJ, et al. AKAP9 is a genetic modifier of congenital long- QT syndrome type 1. Circ Cardiovasc Genet. 2014;7:599–606. unit of protein kinase A (PKA) determining the localization of 2. Chen L, Marquardt ML, Tester DJ, Sampson KJ, Ackerman MJ, protein kinase A and enzymes that regulate the PKA pathway, Kass RS. Mutation of an A-kinase-anchoring protein causes long- such as phosphatases or phosphodiesterases, and other ki- QT syndrome. Proc Natl Acad Sci U S A. 2007;104:20990–5. nases, such as PKC and PKD. In the heart, AKAP-mediated macromolecular complexes coordinate three critical ion chan- Publisher’snoteSpringer Nature remains neutral with regard to nel proteins: the ryanodine receptor, or intracellular calcium- jurisdictional claims in published maps and institutional affiliations..