Autosomal Recessive Catecholamine- or Exercise-Induced Polymorphic Ventricular Tachycardia: Clinical Features and Assignment of the Disease Gene to Chromosome 1p13-21
Open accessAbstract
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 β-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 θ=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.
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In patients with CPVT, 60% have a mutation in either RyR2 or CASQ2.
“In patients with CPVT, 60% have a mutation in either the gene encoding the cardiac ryanodine receptor (RyR2) (autosomal dominant) or in the cardiac calsequestrin gene (CASQ2) (autosomal recessive) (330–333).”
From 2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope (2017) · cites this paper as [333]
The Abstract (page not provided) reports RyR2 mutations in families with the dominant form of the disorder, and describes the Bedouin families’ form as autosomal recessive. It does not identify CASQ2 as the recessive gene or state that 60% of patients with CPVT have mutations in either gene; it maps the recessive disease locus to chromosome 1p13–21. (LLM, conf=0.86)
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References 16 · Cited by 266
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- Authors
- Lahat, H., Eldar, M., Levy-Nissenbaum, E., Bahan, T., Friedman, E., Khoury, A., Lorber, A., Kastner, D. L., Goldman, B., & Pras, E.
- Affiliations
- National Institutes of Health (US)
- 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...
- Venue
- Circulation
- Published
- 2001-06-12
- Volume
- 103
- Issue
- 23
- Pages
- 2822-2827
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W1988998632
- Cited by
- 266
- References
- 16
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 6 · 2023: 2 · 2022: 9 · 2021: 5 · 2020: 9 · 2019: 7 · 2018: 3 · 2017: 12 · 2016: 8 · 2015: 8 · 2014: 14 · 2013: 20 · 2012: 24
- FWCI
- 7.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Effects of Exercise
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiomyopathy and Myosin Studies
- Keywords
- catecholaminergic polymorphic ventricular tachycardia, autosomal recessive inheritance, exercise-induced ventricular arrhythmias, sudden cardiac death, syncope, seizures, linkage mapping, KCND3, beta-blocker therapy, Bedouin family, consanguinity
- MeSH terms
- Adolescent, Adrenergic beta-Agonists, Adrenergic beta-Antagonists, Bradycardia, Catecholamines, Child, Chromosome Mapping, Chromosomes, Human, Pair 1, Consanguinity, Electrocardiography, Exercise Test, Physical Exertion, Genes, Recessive, Genetic Markers, Humans, Isoproterenol, Israel, Genetic Linkage, Lod Score, Seizures, Syncope, Comorbidity, Death, Sudden, Cardiac, Tachycardia, Ventricular, Arabs
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