Plakophilin-2 p.S140Fc.419C>T and Risk of Heart Failure and Arrhythmias
in the General Population
Supplementary data
Alex Hørby Christensen MD PhD1; Pia Rørbæk Kamstrup MD PhD2; Estelle Gandjbakhch MD PhD3; Marianne Benn MD DMSc4; Jan Skov Jensen MD DMSc5; Henning Bundgaard MD DMSc6; Eric Villard PhD3; Anne Tybjærg-Hansen MD DMSc7,8
1Department of Cardiology, Bispebjerg Hospital; 2Department of Clinical Biochemistry, Herlev Hospital; 3Inserm/UMR_S1166, ICAN, Hôpital Pitié-Salpêtrière, Paris, France; 4Department of Clinical Biochemistry, Gentofte Hospital;5Department ofCardiology, Gentofte Hospital; 6Unit for Inherited Cardiac Diseases, Department of Cardiology, The Heart Centre, Rigshospitalet; 7Department of Clinical Biochemistry, Rigshospitalet; 8The Copenhagen City Heart Study, Frederiksberg Hospital; 1,2,4-8Copenhagen University Hospitals and Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
Corresponding author:
Anne Tybjærg-Hansen MD DMSc
Professor, Chief Physician
Department of Clinical Biochemistry KB3011, Section for Molecular Genetics
Rigshospitalet, Copenhagen University Hospital
Blegdamsvej 9, DK-2100 Copenhagen, Denmark
Phone: +45 35454159, Fax: +45 35454160, email:
Supplementary Table 1. Overview of studies associating PKP2p.S140Fc.419C>T with cardiomyopathy and arrhythmia syndromes.Probands / Controls
Phenotype / Carriers / Non-carriers / Carriers / Non-carriers / Comments
Gerull et al, 2004(1) / ARVC / 1 / 119 / 0 / 250
Syrris et al, 2006(2) / ARVC / 1 / 99 / 0 / 200 / Incomplete cosegregation.
Dalal et al, 2006(3) / ARVC / 1 / 57 / 0 / 0
Koopmaan et al, 2007(4) / BS / 1 / 37 / 1 / 75 / Reported as a polymorphism.
Sen-Chowdhry et al, 2007(5) / ARVC / 2 / 198 / 0 / 0 / Incomplete cosegregation.
Sen-Chowdhry et al, 2008(6) / LDAC / 1 / 41 / 0 / 0
Behr et al, 2008(7) / SADS / 1 / 56 / 0 / 200
den Haan et al, 2009(8) / ARVC / 1 / 99 / 0 / 0 / Previously reported by Dalal et al. Patient also carried PKP2 c.2146-1G>C and DSG2p.V56Mc.166G>A variants.
Xu et al, 2010(9) / ARVC / 1 / 197 / 0 / 700 / Previously reported by Dalal et al. Patient also carried PKP2 c.2146-1G>C and DSG2c.166G>Ap.V56M variants.
Tan et al, 2010(10) / ARVC / 1 / 111 / 0 / 0 / Previously reported by Dalal et al. Patient also carried PKP2 c.2146-1G>C and DSG2c.166G>Ap.V56M variants.
Christensen et al,2010(11) / ARVC / 3 / 60 / 5 / 645 / Lack of cosegregation. Reported as GVUS.
Fressart et al, 2010(12) / ARVC / 1 / 134 / 0 / 300 / Homozygous. Reported as GVUS.
Christensen et al, 2010(13) / ARVC / 3 / 62 / 5 / 645 / Previously reported by Christensen et al. One patient also carried DSC2p.E2Kc.4G>A variant.
Elliott et al, 2010(14) / DCM / 3 / 97 / 0 / 200 / One PKP2p.S140Fc.419C>T patient also carried DSPp.A2712Tc.8134G>A variant
Quarta et al, 2011(15) / ARVC / 2 / 98 / 0 / 300 / Previously reported by Syrris et al. Incomplete cosegregation.
Garcia-Pavia et al, 2011(16) / DCM / 1 / 88 / 0 / 200
Groeneweg et al, 2013(17) / LDAC / 1(6 in family) / - / - / - / PKP2p.S140Fc.419C>T and PLN c.40_42delAGA identified in a family. Six members carried PKP2p.S140Fc.419C>T which did not segregate with disease.
Present publication, 20142015 / GP + Mixed / 5 / 512 / 98 / 10309 / Two probands carried mutations in other disease-associated genes.
ARVC: Arrhythmogenic right ventricular cardiomyopathy; BS: Brugada Syndrome; DCM: Dilated cardiomyopathy; GP: General population; GVUS: Genetic variant of unknown significance; LDAC: Left dominant arrhythmogenic cardiomyopathy; SADS: Sudden arrhythmic death syndrome.
Supplementary Table 2. Primers used for in vitro analyses
PKP2_F_cDNA / 5’-ccgcgaattccagaggcag-3’
PKP2_R_cDNA / 5’-ggggatggatccagccgagaatactt-3’
PKP2_F_S140F / 5’-ccgtggaagaaaggttcttgaggcatcctctg-3’
PKP2_R_S140F / 5’-cagaggatgcctcaagaacctttcttccacgg-3’
Supplementary Figure 1. Sequence alignment and in silicopredictions of p.S140F.
H.sapiens / E / R / S / L / R
P.troglodytes / E / R / S / L / R
M.mulatta / I / T / S / A / S
B.taurus / E / R / F / F / R
C.familaris / E / R / S / L / R
M.musculus / E / R / S / W / R
G.gallus / E / R / T / Q / R
Polyphen-2 / SIFT / Panther / Mutation Taster
In silico prediction / Benign / Tolerated / -2.3* / Polymorphism
*value less than -3 considered functional
Supplementary references
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