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(Circulation. 2001;103:2822.)
© 2001 American Heart Association, Inc.

Clinical Investigation and Reports

Autosomal Recessive Catecholamine- or Exercise-Induced Polymorphic Ventricular Tachycardia

Clinical Features and Assignment of the Disease Gene to Chromosome 1p13-21

Hadas Lahat, MSc; Michael Eldar, MD; Etgar Levy-Nissenbaum, BSc; Tangiz Bahan, PhD; Eitan Friedman, MD; Asad Khoury, MD; Avraham Lorber, MD; Daniel L. Kastner, MD, PhD; Boleslaw Goldman, MD; Elon Pras, MD

From the Danek Gartner Institute of Human Genetics (H.L., E.L-N., T.B., B.G., E.P.), Neufeld Cardiac Research Institute (H.L., M.E.), and Susanne Levy Gertner Oncogenetics Unit (E.F.), Sheba Medical Center, Tel Hashomer, Israel (affiliated with the Sackler School of Medicine, Tel Aviv University, Israel); the Institute of Pediatric Cardiology, Rambam Medical Center, Haifa, Israel (A.K., A.L.); and the Genetic Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Md (D.L.K.).

Correspondence to Dr Elon Pras, Institute of Human Genetics, Sheba Medical Center, Tel Hashomer 52621, Israel ( E-mail epras{at}cc.tau.ac.il) or to Prof Michael Eldar, Henry Neufeld Cardiac Research Institute, Sheba Medical Center, Tel Hashomer 52621, Israel (

Background—Catecholaminergic polymorphic ventricular tachycardia (PVT) is characterized by episodes of syncope, seizures, or sudden death in response to physiological or emotional stress. In 2 families with autosomal dominant inheritance, the disease gene was mapped to chromosome 1q42-43. The objectives of this study were to characterize the clinical features of the disease in a Bedouin tribe from Israel and to map the disease gene.

Methods and Results—In this Bedouin tribe, 9 children (age, 7±4 years) from 7 related families have died suddenly during the past decade, and 12 other children suffered from recurrent syncope and seizures starting at the age of 6±3 years. Parents of affected individuals were asymptomatic and were all related (first-, second-, or third-degree cousins). Segregation analysis suggested autosomal recessive inheritance. All 12 symptomatic patients and 1 asymptomatic sibling (mean age, 13±7 years) were found to have a relative resting bradycardia (64±13 bpm, versus 93±12 bpm in the unaffected siblings), as well as PVT induced by treadmill or isoproterenol infusion and appearing at a mean sinus rate of 110±10 bpm. Patients responded favorably to treatment with ß-blockers. A genome-wide search using polymorphic DNA markers mapped the disease locus to a 16-megabase interval on chromosome 1p13-21. A maximal lod score of 8.24 was obtained with D1S189 at =0.00. Sequencing of KCND3, a gene that encodes an I_tO potassium channel transporter, did not reveal any significant sequence alterations.

Conclusions—This unique form of autosomal recessive PVT affects young children and may be lethal if left untreated. Linkage analysis maps this disorder to chromosome 1p13-21.

Key Words: tachycardia • genetics • mapping • death, sudden • syncope

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