Identification of a Gene Responsible for Familial Wolff–Parkinson–White Syndrome
Michael H. Gollob, M.D., Martin S. Green, M.D., Anthony S.-L. Tang, M.D., Tanya Gollob, R.N., Akihiko Karibe, M.D., Al-Sayegh Hassan, M.D., Ferhaan Ahmad, M.D., Ryan Lozado, B.S., Gopi Shah, M.D., Lameh Fananapazir, M.D., Linda L. Bachinski, Ph.D., Terry Tapscott, B.S., Oscar Gonzales, B.S., David Begley, M.D., Saidi Mohiddin, M.D., and Robert Roberts, M.D.
Background The Wolff–Parkinson–White syndrome, witha prevalence in Western countries of 1.5 to 3.1 per 1000 persons,causes considerable morbidity and may cause sudden death. Weidentified two families in which the Wolff–Parkinson–Whitesyndrome segregated as an autosomal dominant disorder.
Methods We studied 70 members of the two families (57 in Family1 and 13 in Family 2). The subjects underwent 12-lead electrocardiographyand two-dimensional echocardiography. Genotyping mapped thegene responsible to 7q34–q36, a locus previously identifiedto be responsible for an inherited form of Wolff–Parkinson–Whitesyndrome. Candidate genes were identified, sequenced, and analyzedin normal and affected family members to identify the disease-causinggene.
Results A total of 31 members (23 from Family 1 and 8 from Family2) had the Wolff–Parkinson–White syndrome. Affectedmembers of both families had ventricular preexcitation withconduction abnormalities and cardiac hypertrophy. The maximalcombined two-point lod score was 9.82 at a distance of 5 cMfrom marker D7S636, which confirmed the linkage of the genein both families to 7q34–q36. Haplotype analysis indicatedthat there were no alleles in common in the two families atthis locus, suggesting that the two families do not have a commonfounder. We identified a missense mutation in the gene thatencodes the 2 regulatory subunit of AMP-activated protein kinase(PRKAG2). The mutation results in the substitution of glutaminefor arginine at residue 302 in the protein.
Conclusions The identification of this genetic defect has importantimplications for elucidating the pathogenesis of ventricularpreexcitation. Further understanding of how this molecular defectleads to supraventricular arrhythmias could influence the developmentof specific therapies for other forms of supraventricular arrhythmia.
Source Information
From the Section of Cardiology, Baylor College of Medicine, Houston (M.H.G., T.G., A.K., F.A., R.L., G.S., L.L.B., R.R.); the University of Ottawa Heart Institute, Ottawa, Ont., Canada (M.S.G., A.S.-L.T., A.-S.H.); and the Inherited Heart Disease Section, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md. (L.F.).
Other authors were Terry Tapscott, B.S., and Oscar Gonzales, B.S. (Section of Cardiology, Baylor College of Medicine, Houston); and David Begley, M.D., and Saidi Mohiddin, M.D. (Inherited Heart Disease Section, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md.).
Address reprint requests to Dr. Roberts at the Department of Medicine, Section of Cardiology, 6550 Fannin, MS SM 677, Baylor College of Medicine, Houston, TX 77030, or at rroberts{at}bcm.tmc.edu.
Watkins, H, Ashrafian, H, McKenna, W J
(2008). The genetics of hypertrophic cardiomyopathy: Teare redux. Heart
94: 1264-1268
[Full Text]
Momcilovic, M., Iram, S. H., Liu, Y., Carlson, M.
(2008). Roles of the Glycogen-binding Domain and Snf4 in Glucose Inhibition of SNF1 Protein Kinase. J. Biol. Chem.
283: 19521-19529
[Abstract][Full Text]
Hahurij, N. D., Gittenberger-De Groot, A. C., Kolditz, D. P., Bokenkamp, R., Schalij, M. J., Poelmann, R. E., Blom, N. A.
(2008). Accessory Atrioventricular Myocardial Connections in the Developing Human Heart: Relevance for Perinatal Supraventricular Tachycardias. Circulation
117: 2850-2858
[Abstract][Full Text]
Young, L. H.
(2008). AMP-Activated Protein Kinase Conducts the Ischemic Stress Response Orchestra. Circulation
117: 832-840
[Full Text]
Wolf, C. M., Arad, M., Ahmad, F., Sanbe, A., Bernstein, S. A., Toka, O., Konno, T., Morley, G., Robbins, J., Seidman, J.G., Seidman, C. E., Berul, C. I.
(2008). Reversibility of PRKAG2 Glycogen-Storage Cardiomyopathy and Electrophysiological Manifestations. Circulation
117: 144-154
[Abstract][Full Text]
Folmes, K. D., Witters, L. A., Allard, M. F., Young, M. E., Dyck, J. R. B.
(2007). The AMPK {gamma}1 R70Q mutant regulates multiple metabolic and growth pathways in neonatal cardiac myocytes. Am. J. Physiol. Heart Circ. Physiol.
293: H3456-H3464
[Abstract][Full Text]
Sproule, D. M., Kaufmann, P., Engelstad, K., Starc, T. J., Hordof, A. J., De Vivo, D. C.
(2007). Wolff-Parkinson-White Syndrome in Patients With MELAS. Arch Neurol
64: 1625-1627
[Abstract][Full Text]
Stephenson, E. A., Berul, C. I.
(2007). Electrophysiological Interventions for Inherited Arrhythmia Syndromes. Circulation
116: 1062-1080
[Full Text]
Charron, P., Genest, M., Richard, P., Komajda, M., Pochmalicki, G.
(2007). A familial form of conduction defect related to a mutation in the PRKAG2 gene. Europace
9: 597-600
[Abstract][Full Text]
Viana, R., Towler, M. C., Pan, D. A., Carling, D., Viollet, B., Hardie, D. G., Sanz, P.
(2007). A Conserved Sequence Immediately N-terminal to the Bateman Domains in AMP-activated Protein Kinase {gamma} Subunits Is Required for the Interaction with the beta Subunits. J. Biol. Chem.
282: 16117-16125
[Abstract][Full Text]
Townley, R., Shapiro, L.
(2007). Crystal Structures of the Adenylate Sensor from Fission Yeast AMP-Activated Protein Kinase. Science
315: 1726-1729
[Abstract][Full Text]
Arad, M., Seidman, C. E., Seidman, J.G.
(2007). AMP-Activated Protein Kinase in the Heart: Role During Health and Disease. Circ. Res.
100: 474-488
[Abstract][Full Text]
Dolinsky, V. W., Dyck, J. R. B.
(2006). Role of AMP-activated protein kinase in healthy and diseased hearts. Am. J. Physiol. Heart Circ. Physiol.
291: H2557-H2569
[Abstract][Full Text]
Xie, M., Zhang, D., Dyck, J. R. B., Li, Y., Zhang, H., Morishima, M., Mann, D. L., Taffet, G. E., Baldini, A., Khoury, D. S., Schneider, M. D.
(2006). A pivotal role for endogenous TGF-beta-activated kinase-1 in the LKB1/AMP-activated protein kinase energy-sensor pathway. Proc. Natl. Acad. Sci. USA
103: 17378-17383
[Abstract][Full Text]
Yu, H., Hirshman, M. F., Fujii, N., Pomerleau, J. M., Peter, L. E., Goodyear, L. J.
(2006). Muscle-specific overexpression of wild type and R225Q mutant AMP-activated protein kinase {gamma}3-subunit differentially regulates glycogen accumulation. Am. J. Physiol. Endocrinol. Metab.
291: E557-E565
[Abstract][Full Text]
Petersen, S. E., Wiesmann, F., Hudsmith, L. E., Robson, M. D., Francis, J. M., Selvanayagam, J. B., Neubauer, S., Channon, K. M.
(2006). Functional and Structural Vascular Remodeling in Elite Rowers Assessed by Cardiovascular Magnetic Resonance. J Am Coll Cardiol
48: 790-797
[Abstract][Full Text]
Dyck, J. R. B., Lopaschuk, G. D.
(2006). AMPK alterations in cardiac physiology and pathology: enemy or ally?. J. Physiol.
574: 95-112
[Abstract][Full Text]
Davies, J. K., Wells, D. J., Liu, K., Whitrow, H. R., Daniel, T. D., Grignani, R., Lygate, C. A., Schneider, J. E., Noel, G., Watkins, H., Carling, D.
(2006). Characterization of the role of {gamma}2 R531G mutation in AMP-activated protein kinase in cardiac hypertrophy and Wolff-Parkinson-White syndrome. Am. J. Physiol. Heart Circ. Physiol.
290: H1942-H1951
[Abstract][Full Text]
Hattori, Y., Akimoto, K., Nishikimi, T., Matsuoka, H., Kasai, K.
(2006). Activation of AMP-Activated Protein Kinase Enhances Angiotensin II-Induced Proliferation in Cardiac Fibroblasts. Hypertension
47: 265-270
[Abstract][Full Text]
Roberts, R.
(2006). Genomics and Cardiac Arrhythmias. J Am Coll Cardiol
47: 9-21
[Abstract][Full Text]
Ignoul, S., Eggermont, J.
(2005). CBS domains: structure, function, and pathology in human proteins. Am. J. Physiol. Cell Physiol.
289: C1369-C1378
[Abstract][Full Text]
Ahmad, F., Arad, M., Musi, N., He, H., Wolf, C., Branco, D., Perez-Atayde, A. R., Stapleton, D., Bali, D., Xing, Y., Tian, R., Goodyear, L. J., Berul, C. I., Ingwall, J. S., Seidman, C. E., Seidman, J.G.
(2005). Increased {alpha}2 Subunit-Associated AMPK Activity and PRKAG2 Cardiomyopathy. Circulation
112: 3140-3148
[Abstract][Full Text]
Terai, K., Hiramoto, Y., Masaki, M., Sugiyama, S., Kuroda, T., Hori, M., Kawase, I., Hirota, H.
(2005). AMP-Activated Protein Kinase Protects Cardiomyocytes against Hypoxic Injury through Attenuation of Endoplasmic Reticulum Stress. Mol. Cell. Biol.
25: 9554-9575
[Abstract][Full Text]
Chandra, M., Tschirgi, M. L., Tardiff, J. C.
(2005). Increase in tension-dependent ATP consumption induced by cardiac troponin T mutation. Am. J. Physiol. Heart Circ. Physiol.
289: H2112-H2119
[Abstract][Full Text]
Yang, Z., McMahon, C. J., Smith, L. R., Bersola, J., Adesina, A. M., Breinholt, J. P., Kearney, D. L., Dreyer, W. J., Denfield, S. W., Price, J. F., Grenier, M., Kertesz, N. J., Clunie, S. K., Fernbach, S. D., Southern, J. F., Berger, S., Towbin, J. A., Bowles, K. R., Bowles, N. E.
(2005). Danon Disease as an Underrecognized Cause of Hypertrophic Cardiomyopathy in Children. Circulation
112: 1612-1617
[Abstract][Full Text]
Zou, L., Shen, M., Arad, M., He, H., Lofgren, B., Ingwall, J. S., Seidman, C. E., Seidman, J. G., Tian, R.
(2005). N488I Mutation of the {gamma}2-Subunit Results in Bidirectional Changes in AMP-Activated Protein Kinase Activity. Circ. Res.
97: 323-328
[Abstract][Full Text]
Kaab, S., Schulze-Bahr, E.
(2005). Susceptibility genes and modifiers for cardiac arrhythmias. Cardiovasc Res
67: 397-413
[Abstract][Full Text]
Roberts, R., Sigwart, U.
(2005). Current Concepts of the Pathogenesis and Treatment of Hypertrophic Cardiomyopathy. Circulation
112: 293-296
[Full Text]
Boullin, J, Morgan, J M
(2005). The development of cardiac rhythm. Heart
91: 874-875
[Full Text]
Beery, T. T.
(2005). The Genetics of Cardiac Arrhythmias. Biol Res Nurs
6: 249-261
[Abstract]
Murphy, R. T., Mogensen, J., McGarry, K., Bahl, A., Evans, A., Osman, E., Syrris, P., Gorman, G., Farrell, M., Holton, J. L., Hanna, M. G., Hughes, S., Elliott, P. M., MacRae, C. A., McKenna, W. J.
(2005). Adenosine monophosphate-activated protein kinase disease mimicks hypertrophic cardiomyopathy and Wolff-Parkinson-White syndrome: Natural history. J Am Coll Cardiol
45: 922-930
[Abstract][Full Text]
Alpert, N. R., Mohiddin, S. A., Tripodi, D., Jacobson-Hatzell, J., Vaughn-Whitley, K., Brosseau, C., Warshaw, D. M., Fananapazir, L.
(2005). Molecular and phenotypic effects of heterozygous, homozygous, and compound heterozygote myosin heavy-chain mutations. Am. J. Physiol. Heart Circ. Physiol.
288: H1097-H1102
[Abstract][Full Text]
Arad, M., Maron, B. J., Gorham, J. M., Johnson, W. H. Jr., Saul, J. P., Perez-Atayde, A. R., Spirito, P., Wright, G. B., Kanter, R. J., Seidman, C. E., Seidman, J.G.
(2005). Glycogen Storage Diseases Presenting as Hypertrophic Cardiomyopathy. NEJM
352: 362-372
[Abstract][Full Text]
Sidhu, J. S., Rajawat, Y. S., Rami, T. G., Gollob, M. H., Wang, Z., Yuan, R., Marian, A.J., DeMayo, F. J., Weilbacher, D., Taffet, G. E., Davies, J. K., Carling, D., Khoury, D. S., Roberts, R.
(2005). Transgenic Mouse Model of Ventricular Preexcitation and Atrioventricular Reentrant Tachycardia Induced by an AMP-Activated Protein Kinase Loss-of-Function Mutation Responsible for Wolff-Parkinson-White Syndrome. Circulation
111: 21-29
[Abstract][Full Text]
Smits, J. P.P., Veldkamp, M. W., Wilde, A. A.M.
(2005). Mechanisms of inherited cardiac conduction disease. Europace
7: 122-137
[Abstract][Full Text]
Maron, B. J., Seidman, J.G., Seidman, C. E.
(2004). Proposal for contemporary screening strategies in families with hypertrophic cardiomyopathy. J Am Coll Cardiol
44: 2125-2132
[Abstract][Full Text]
Chan, A. Y. M., Soltys, C.-L. M., Young, M. E., Proud, C. G., Dyck, J. R. B.
(2004). Activation of AMP-activated Protein Kinase Inhibits Protein Synthesis Associated with Hypertrophy in the Cardiac Myocyte. J. Biol. Chem.
279: 32771-32779
[Abstract][Full Text]
Nagata, D., Takeda, R., Sata, M., Satonaka, H., Suzuki, E., Nagano, T., Hirata, Y.
(2004). AMP-Activated Protein Kinase Inhibits Angiotensin II-Stimulated Vascular Smooth Muscle Cell Proliferation. Circulation
110: 444-451
[Abstract][Full Text]
Zipes, D. P.
(2004). The year in electrophysiology. J Am Coll Cardiol
43: 1306-1314
[Full Text]
Yu, H., Fujii, N., Hirshman, M. F., Pomerleau, J. M., Goodyear, L. J.
(2004). Cloning and characterization of mouse 5'-AMP-activated protein kinase {gamma}3 subunit. Am. J. Physiol. Cell Physiol.
286: C283-C292
[Abstract][Full Text]
Committee Members, , Blomstrom-Lundqvist, C., Scheinman, M. M., Aliot, E. M., Alpert, J. S., Calkins, H., Camm, A. J., Campbell, W. B., Haines, D. E., Kuck, K. H., Lerman, B. B., Miller, D. D., Shaeffer, C. W. Jr, Stevenson, W. G., Tomaselli, G. F., Task Force Members, , Antman, E. M., Smith, S. C. Jr, Alpert, J. S., Faxon, D. P., Fuster, V., Gibbons, R. J., Gregoratos, G., Hiratzka, L. F., Hunt, S. A., Jacobs, A. K., Russell, R. O. Jr, ESC Committee for Practice Guidelines Members, , Priori, S. G., Blanc, J.-J., Budaj, A., Burgos, E. F., Cowie, M., Deckers, J. W., Garcia, M. A. A., Klein, W. W., Lekakis, J., Lindahl, B., Mazzotta, G., Morais, J. C. A., Oto, A., Smiseth, O., Trappe, H.-J.
(2003). ACC/AHA/ESC guidelines for the management of patients with supraventricular arrhythmias --executive summary: a report of the American college of cardiology/American heart association task force on practice guidelines and the European society of cardiology committee for practice guidelines (writing committee to develop guidelines for the management of patients with supraventricular arrhythmias) Developed in Collaboration with NASPE-Heart Rhythm Society. J Am Coll Cardiol
42: 1493-1531
[Full Text]
Blomstrom-Lundqvist, C., Scheinman, M. M., Aliot, E. M., Alpert, J. S., Calkins, H., Camm, A. J., Campbell, W. B., Haines, D. E., Kuck, K. H., Lerman, B. B., Miller, D. D., Shaeffer, C. W. Jr, Stevenson, W. G., Tomaselli, G. F., Antman, E. M., Smith, S. C. Jr, Alpert, J. S., Faxon, D. P., Fuster, V., Gibbons, R. J., Gregoratos, G., Hiratzka, L. F., Hunt, S. A., Jacobs, A. K., Russell, R. O. Jr, Priori, S. G., Blanc, J.-J., Budaj, A., Burgos, E. F., Cowie, M., Deckers, J. W., Garcia, M. A. A., Klein, W. W., Lekakis, J., Lindahl, B., Mazzotta, G., Morais, J. C. A., Oto, A., Smiseth, O., Trappe, H.-J., Committee Members, , Task Force Members, , ESC Committee for Practice Guidelines Members,
(2003). ACC/AHA/ESC Guidelines for the Management of Patients With Supraventricular Arrhythmias*--Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Supraventricular Arrhythmias). Circulation
108: 1871-1909
[Full Text]
Committee Members, , Blomstrom-Lundqvist, C., Scheinman, M. M, Aliot, E. M, Alpert, J. S, Calkins, H., Camm, A.J., Campbell, W.B., Haines, D. E, Kuck, K. H, Lerman, B. B, Miller, D.D., Shaeffer, C. W. Jr, Stevenson, W. G, Tomaselli, G. F, Task Force Members, , Antman, E. M, Smith, S. C Jr, Alpert, J. S, Faxon, D. P, Fuster, V., Gibbons, R. J, Gregoratos, G., Hiratzka, L. F, Hunt, S. A., Jacobs, A. K, Russell, R. O Jr, ESC Committee for Practice Guidelines Members, , Priori, S. G, Blanc, J.-J., Budaj, A., Burgos, E. F., Cowie, M., Deckers, J. W., Garcia, M. A. A., Klein, W. W, Lekakis, J., Lindahl, B., Mazzotta, G., Morais, J. C. A., Oto, A., Smiseth, O., Trappe, H.-J.
(2003). ACC/AHA/ESC guidelines for the management of patients with supraventricular arrhythmias--executive summary: A Report of the American College of Cardiology/American HeartAssociation Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines(Writing Committee to Develop Guidelines for the Management of Patients With Supraventricular Arrhythmias)Developed in collaboration with NASPE-Heart Rhythm Society. Eur Heart J
24: 1857-1897
[Full Text]
Patel, V. V., Arad, M., Moskowitz, I. P. G., Maguire, C. T., Branco, D., Seidman, J. G., Seidman, C. E., Berul, C. I.
(2003). Electrophysiologic characterization and postnatal development of ventricular pre-excitation in a mouse model of cardiachypertrophy and Wolff-Parkinson-White syndrome. J Am Coll Cardiol
42: 942-951
[Abstract][Full Text]
Arad, M., Moskowitz, I. P., Patel, V. V., Ahmad, F., Perez-Atayde, A. R., Sawyer, D. B., Walter, M., Li, G. H., Burgon, P. G., Maguire, C. T., Stapleton, D., Schmitt, J. P., Guo, X.X., Pizard, A., Kupershmidt, S., Roden, D. M., Berul, C. I., Seidman, C. E., Seidman, J.G.
(2003). Transgenic Mice Overexpressing Mutant PRKAG2 Define the Cause of Wolff-Parkinson-White Syndrome in Glycogen Storage Cardiomyopathy. Circulation
107: 2850-2856
[Abstract][Full Text]
Crilley, J. G., Boehm, E. A., Blair, E., Rajagopalan, B., Blamire, A. M., Styles, P., McKenna, W. J., Ostman-Smith, I., Clarke, K., Watkins, H.
(2003). Hypertrophic cardiomyopathy due to sarcomeric gene mutations is characterized by impaired energy metabolism irrespective of the degree of hypertrophy. J Am Coll Cardiol
41: 1776-1782
[Abstract][Full Text]
Roberts, R., Marian, A. J.
(2003). Can an energy-deficient heart grow bigger and stronger?. J Am Coll Cardiol
41: 1783-1785
[Full Text]
Richard, P., Charron, P., Carrier, L., Ledeuil, C., Cheav, T., Pichereau, C., Benaiche, A., Isnard, R., Dubourg, O., Burban, M., Gueffet, J.-P., Millaire, A., Desnos, M., Schwartz, K., Hainque, B., Komajda, M., for the EUROGENE Heart Failure Project,
(2003). Hypertrophic Cardiomyopathy: Distribution of Disease Genes, Spectrum of Mutations, and Implications for a Molecular Diagnosis Strategy. Circulation
107: 2227-2232
[Abstract][Full Text]
Hallows, K. R., Kobinger, G. P., Wilson, J. M., Witters, L. A., Foskett, J. K.
(2003). Physiological modulation of CFTR activity by AMP-activated protein kinase in polarized T84 cells. Am. J. Physiol. Cell Physiol.
284: C1297-C1308
[Abstract][Full Text]
Light, P. E., Wallace, C. H.R., Dyck, J. R.B.
(2003). Constitutively Active Adenosine Monophosphate-Activated Protein Kinase Regulates Voltage-Gated Sodium Channels in Ventricular Myocytes. Circulation
107: 1962-1965
[Abstract][Full Text]
Jongbloed, R. J., Marcelis, C. L., Doevendans, P. A., Schmeitz-Mulkens, J. M., Van Dockum, W. G., Geraedts, J. P., Smeets, H. J.
(2003). Variable clinical manifestation of a novel missense mutation in the alpha-tropomyosin (TPM1) gene in familial hypertrophic cardiomyopathy. J Am Coll Cardiol
41: 981-986
[Abstract][Full Text]
Watkins, H.
(2003). Genetic Clues to Disease Pathways in Hypertrophic and Dilated Cardiomyopathies. Circulation
107: 1344-1346
[Full Text]
Daniel, T., Carling, D.
(2002). Functional Analysis of Mutations in the gamma 2 Subunit of AMP-activated Protein Kinase Associated with Cardiac Hypertrophy and Wolff-Parkinson-White Syndrome. J. Biol. Chem.
277: 51017-51024
[Abstract][Full Text]
Arad, M., Seidman, J.G., Seidman, C. E.
(2002). Phenotypic diversity in hypertrophic cardiomyopathy. Hum Mol Genet
11: 2499-2506
[Abstract][Full Text]
Fatkin, D., Graham, R. M.
(2002). Molecular Mechanisms of Inherited Cardiomyopathies. Physiol. Rev.
82: 945-980
[Abstract][Full Text]
Hwang, J.-J., Allen, P. D., Tseng, G. C., Lam, C.-W., Fananapazir, L., Dzau, V. J., Liew, C.-C.
(2002). Microarray gene expression profiles in dilated and hypertrophic cardiomyopathic end-stage heart failure. Physiol. Genomics
10: 31-44
[Abstract][Full Text]
Gollob, M.H., Roberts, R.
(2002). AMP-activated protein kinase and familial Wolff-Parkinson-White syndrome: new perspectives on heart development and arrhythmogenesis. Eur Heart J
23: 679-681
[Full Text]
Maron, B. J.
(2002). Hypertrophic Cardiomyopathy: A Systematic Review. JAMA
287: 1308-1320
[Abstract][Full Text]
Kelly, D. P.
(2002). Peroxisome Proliferator-Activated Receptor {alpha} as a Genetic Determinant of Cardiac Hypertrophic Growth: Culprit or Innocent Bystander?. Circulation
105: 1025-1027
[Full Text]
Doevendans, P. A., Wellens, H. J.
(2001). Wolff-Parkinson-White Syndrome: A Genetic Disease?. Circulation
104: 3014-3016
[Full Text]
Gollob, M. H., Seger, J. J., Gollob, T. N., Tapscott, T., Gonzales, O., Bachinski, L., Roberts, R.
(2001). Novel PRKAG2 Mutation Responsible for the Genetic Syndrome of Ventricular Preexcitation and Conduction System Disease With Childhood Onset and Absence of Cardiac Hypertrophy. Circulation
104: 3030-3033
[Abstract][Full Text]
Anderson, K. P., Vidaillet, H. J. Jr., Josephson, M. E., Gollob, M. H., Green, M. S., Roberts, R.
(2001). A Gene Responsible for Familial Wolff-Parkinson-White Syndrome. NEJM
345: 1063-1064
[Full Text]
A correction has been published: N Engl J Med 2001;345(7):552.
2 regulatory subunit of AMP-activated protein kinase (PRKAG2). The mutation results in the substitution of glutamine for arginine at residue 302 in the protein. 
Previous
