Cardiac ion channel gene mutations in Greek long QT syndrome patients

• Autorzy: Kotta C-M. , Anastasakis A. , Gatzoulis K. , Papagiannis J. , Geleris P. , Stefanadis C.
• Języki publikacji: EN

Abstrakty

EN

The long QT syndrome (LQTS) is an inherited cardiac arrhythmia that may lead to sudden death in the absence of structural heart disease. Mutations in the cardiac potassium and sodium channel genes can be found in approximately 70% of patients with a highly probable clinical diagnosis. In this study, we aimed to genotype and explore the yield of genetic testing of LQTS patients from Greece, for whom there are no collective published data available. We clinically evaluated and genetically screened 17 unrelated patients for mutations in the KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 cardiac ion channel genes. Genetic testing was positive in 6 out of 8 patients with a highly probable clinical diagnosis of LQTS and negative for all the other patients. Two patients carried KCNQ1 mutations (c.580G>C, c.1022C>T), while 4 patients carried KCNH2 mutations (c.202T>C, c.1714G>A, c.3103delC, c.3136C>T). To the best of our knowledge, the last mentioned mutation (c.3136C>T) is novel. Moreover, 27 single-nucleotide polymorphisms (SNPs) were detected, 5 of which are novel. Our preliminary data indicate a low genetic diversity of the Greek LQTS genetic pool, and are in accordance with international data that genetic testing of the major LQTS genes is efficient in genotyping the majority of patients with a strong clinical diagnosis. Therefore, the transition of an LQTS genetic screening program from research to the diagnostic setting within our ethnic background is feasible.

Słowa kluczowe

EN

long QT syndrome; genetic testing; mutation; sudden cardiac death; cardiac arrhythmia; arrhythmia; heart disease; Greece; patient; human disease; clinical diagnosis; potassium channel gene; sodium-potassium channel; sodium channel gene

• Wydawca: -
• Czasopismo: Journal of Applied Genetics
• Rocznik: 2010
• Tom: 51
• Numer: 4
• Opis fizyczny: p.515-518,fig.,ref.

Twórcy

autor

Kotta C-M.

• Division of Inherited Cardiovascular Diseases, 1st Department of Cardiology, University of Athens Medical School, Hippokration Hospital, 14 Paloumbioti St., 11476 Athens, Greece

autor

Anastasakis A.

• Division of Inherited Cardiovascular Diseases, 1st Department of Cardiology, University of Athens Medical School, Hippokration Hospital, 14 Paloumbioti St., 11476 Athens, Greece

autor

Gatzoulis K.

• Division of Inherited Cardiovascular Diseases, 1st Department of Cardiology, University of Athens Medical School, Hippokration Hospital, 14 Paloumbioti St., 11476 Athens, Greece

autor

Papagiannis J.

• Pediatric Cardiology Clinic, Mitera General, Maternity & Children's Hospital, Athens, Greece

autor

Geleris P.

• 2nd Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki Medical School, Hippokration Hospital, Thessaloniki, Greece

autor

Stefanadis C.

• Division of Inherited Cardiovascular Diseases, 1st Department of Cardiology, University of Athens Medical School, Hippokration Hospital, 14 Paloumbioti St., 11476 Athens, Greece

Bibliografia

• Anastasakis A, Kotta CM, Kyriakogonas S, Wollnik B, Theopistou A, Stefanadis C, 2006. Phenotype reveals genotype in a Greek long QT syndrome family. Europace 8: 241-244.
• den Dunnen JT, Antonarakis SE, 2000. Mutation nomenclature extensions and suggestions to describe complex mutations: a discussion. Hum Mutat 15: 7-12.
• Gene Connection for the Heart database: a project of the Study Group on Molecular Basis of Arrhythmias, supported by the European Society of Cardiology (Available at www.fsm.it/cardmoc).
• Goldenberg I, Moss AJ, 2008. Long QT syndrome. J Am Coll Cardiol 51: 2291-2300.
• Itoh T, Tanaka T, Nagai R, Kamiya T, Sawayama T, Nakayama T, et al. 1998. Genomic organization and mutational analysis of HERG, a gene responsible for familial long QT syndrome. Hum Genet 102: 435-439.
• Kupershmidt S, Yang T, Chanthaphaychith S, Wang Z, Towbin JA, Roden DM, 2002. Defective human Ether-á-go-go-related gene trafficking linked to an endoplasmic reticulum retention signal in the C terminus. J Biol Chem 277: 27442-27448.
• Napolitano C, Priori SG, Schwartz PJ, Bloise R, Ronchetti E, Nastoli J, et al. 2005. Genetic testing in the long QT syndrome: development and validation of an efficient approach to genotyping in clinical practice. JAMA 294: 2975-2980.
• Neyroud N, Richard P, Vignier N, Donger C, Denjoy I, Demay L, et al. 1999. Genomic organization of the KCNQ1 K+ channel gene and identification of C-terminal mutations in the long-QT syndrome. Circ Res 84: 290-297.
• Phillips KA, Ackerman MJ, Sakowski J, Berul CI, 2005. Cost-effectiveness analysis of genetic testing for familial long QT syndrome in symptomatic index cases. Heart Rhythm 2: 1294-1300.
• Priori SG, Napolitano C, 2006. Role of genetic analyses in cardiology: part I: Mendelian diseases: cardiac channelopathies. Circulation 113: 1130-1135.
• Priori SG, Napolitano C, Schwartz PJ, 1999. Low penetrance in the long QT syndrome: clinical impact. Circulation 99: 529-533.
• Priori SG, Schwartz PJ, Napolitano C, Bloise R, Ronchetti E, Grillo M, et al. 2003. Risk stratification in the long-QT syndrome. N Engl J Med 2003 348: 1866-1874.
• Schwartz PJ, Moss AJ, Vincent GM, Crampton RS, 1993. Diagnostic criteria for the long QT syndrome: an update. Circulation 88: 782-784.
• Splawski 1, Shen J, Timothy KW, Lehmann MH, Priori S, Robinson JL, et al. 2000. Spectrum of mutations in long-QT syndrome genes: KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation 102: 1178-1185.
• Splawski I, Shen J, Timothy KW, Vincent GM, Lehmann MH, Keating MT, 1998. Genomic structure of three long QT syndrome genes: KVLQT1, HERG, and KCNE1. Genomics 51: 86-97.
• Tester DJ, Will ML, Haglund CM, Ackerman MJ, 2005. Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing. Heart Rhythm 2: 507-517.