Founder mutations in inherited cardiac diseases in the Netherlands

105 Pages·2014·16.525 MB·English

by  Arthur A.M. Wilde, J. Peter van Tintelen (eds.)

Arthur A.M. Wilde
J. Peter van Tintelen
Founder mutations in inherited cardiac diseases in
the Netherlands
Edited by
Arthur A.M. Wilde
J. Peter van Tintelen
Founder mutations
in inherited cardiac
diseases in the
Netherlands
With a preface of H.J. Wellens
Houten
ISBN978-90-368-0704-3
©BohnStafleuvanLoghum,partofSpringerMedia,theNetherlands,2014
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V
Preface
Looking back after  years of being engaged in cardiology, I am amazed about the progress made in the
managementofthepatientwithheartdisease,resultinginanimpressivedecreaseinmortalityandmorbidity.
Theunravellingofbasicmechanisms,theclinicalapplicationofnewinformation,andtheessentialcontribu-
tionofmedicaltechnologywerethethreeoverlappingcirclesleadingtothosemajoradvancements.Expand-
ingtheoverlapofthecommonpartofthesethreecircles,thezoneofso-called‘translational’medicine,isa
musttomoveinthefuturefrompalliativetreatment,thebasisofmostofourcurrentactivities,tocurative
therapy and finally to a marked reduction and disappearance of cardiovascular diseases by preventive
measures.
Thecompletionofthemapofthehumangenomeincreasedourexpectationstospeedupthisprocess.Itled
toatorrentofarticlesinthecardiovascularjournalsgoingfrombasicfindingstoclinicalimplications.They
areagoodexampleofthewideningofthe‘translationalzone’mentionedabove.Obviously,mucheffortwill
continuetogointotheidentificationofthedifferentgeneticandenvironmentalfactorsthatplayaroleinthe
developmentandprogressionofcardiacdiseasewiththeultimategoaltocorrectandpreventthesefactors.
Molecular genetics and its translation into clinical application is a complex matter. It is not surprising,
therefore, in our daily medical practice that there is often a lack of understanding of the value of genetic
information,howtoobtainit,andhowtouseit.Thereisalsothefearofstigmatisationofapersonbecauseof
acertaingenetically determined abnormality whichmay lead tosocialisolation and discriminationagainst
healthcare,insurance,andemployment.However,geneticinformationisarapidlyexpandingfield,bothin
the prenatal diagnosis of severe early-onset disorders and in the presymptomatic diagnosis of adult-onset
hereditary diseases. It also helps to identify the clinical and prognostic variants of a disease, although
mysteriesanddilemmasstillpersistbecausenotallpathogenicmutationsinthesamegeneleadtothesame
phenotype,clinicalconsequencesandresponsetotherapy.
Akeyquestionishowtobringthesedevelopmentsclosertothepractisingphysician.Also,howtoeducate
theclinicianthatacertainphenotypeshouldtriggerthequestionofageneticcauseandtostartaninvestiga-
tion.An important stepistomake thephysician familiarwiththefounderapproachtounravel hereditary
transmissionofgeneticallydetermineddiseases.Suchstudiesalsoopenthepossibilitytoidentifytheroleof
geneticmodifiersandtheeffectofexternalfactors.
In the Netherlands, several Dutch investigators have reported their findings on founder mutations from a
widearrayofgeneticallydeterminedcardiovascularabnormalities.Overafive-yearperiodaseriesofarticles
describing these studies were published in the Netherlands Heart Journal. They illustrate how combined
effortsfromdifferentdisciplines,usingbasicandclinicalinformation,canleadtoimportantadvancesinour
knowledgeofhereditarycardiovasculardisease.
Drs Wilde and Van Tintelen, two internationally recognised leaders in the field of genetically determined
cardiovasculardisease,broughtthesearticlestogetherinthisbooklet.Itisnotonlyatributetotheimportant
contribution from Dutch scientists to this field but also required reading for the clinician who wants (and
should!)becomebetterinformedaboutrecentadvancesinthisexcitingarea.
HeinWellens
May

VII
Table of Contents
1 Introduction..................................................................................... 1
ArthurWildeandPetervanTintelen
2 FoundermutationsamongtheDutch ....................................................... 3
MauricePAZeegers,FransvanPoppel,RobertVlietinck,LiesbethSpruijtandHarryOstrer
(EuropeanJournalofHumanGenetics12-2004,591–600)
2.1 Introduction....................................................................................... 4
2.2 Dutchorigins...................................................................................... 4
2.3 DemographicsoftheNetherlands................................................................ 4
2.4 Foundermutations ............................................................................... 6
2.5 Implicationsforclinicalgenetictestingandgenediscovery..................................... 10
2.6 Suggestednextsteps ............................................................................. 11
2.7 Acknowledgements............................................................................... 11
References ........................................................................................ 11
3 RecurrentandFounderMutationsintheNetherlands:theLong-QTSyndrome ...... 13
N.Hofman,R.Jongbloed,P.G.Postema,E.Nannenberg,M.AldersandA.A.M.Wilde
(NetherlandsHeartJournal1-2011)
3.1 Introduction....................................................................................... 14
3.2 Methods........................................................................................... 14
3.3 Results ............................................................................................ 14
3.4 Discussion......................................................................................... 17
3.5 Conclusions ....................................................................................... 18
3.6 Acknowledgement................................................................................ 18
References ........................................................................................ 18
4 FoundermutationsintheNetherlands:SCN5a1795insD,thefirstdescribedarrhyth- 21
miaoverlapsyndromeandoneofthelargestandbestcharacterisedfamiliesworld-
wide ..............................................................................................
P.G.Postema,M.P.VandenBerg,J.P.VanTintelen,F.VandenHeuvel,M.Grundeken,N.Hofman,
W.P.VanderRoest,E.A.Nannenberg,I.P.C.Krapels,C.R.BezzinaandA.A.M.Wilde
(NetherlandsHeartJournal11-2009)
4.1 Introduction....................................................................................... 22
4.2 Theboyandthefamily ........................................................................... 22
4.3 Mutation-ECGrelations ........................................................................... 22
4.4 Clinicalcharacteristics ............................................................................ 23
4.5 Treatment......................................................................................... 24
4.6 Geneticmodificationofthearrhythmicsubstrate................................................ 25
4.7 Acknowledgements............................................................................... 26
References ........................................................................................ 26
5 FoundermutationsintheNetherlands:familialidiopathicventricularfibrillationand 29
DPP6..............................................................................................
P.G.Postema,I.Christiaans,N.Hofman,M.Alders,T.T.Koopmann,C.R.Bezzina,P.Loh,
K.Zeppenfeld,P.G.A.VoldersandA.A.M.Wilde
(NetherlandsHeartJournal6-2011)
5.1 Introduction....................................................................................... 30
5.2 Firstclinicalcontactswiththefamily............................................................. 30
5.3 Case1 ............................................................................................. 30
5.4 Case2 ............................................................................................. 30
5.5 Case3 ............................................................................................. 30
5.6 Genefindingstudy................................................................................ 31
5.7 FurtherclinicalevaluationofDPP6haplotypecarriers........................................... 32
5.8 Treatment......................................................................................... 34
VIII TableofContents
5.9 Mechanismsandfurtherstudies.................................................................. 34
5.10 Summary.......................................................................................... 34
5.11 Acknowledgements............................................................................... 34
References ........................................................................................ 34
6 FoundermutationsinhypertrophiccardiomyopathypatientsintheNetherlands ... 37
I.Christiaans,E.A.Nannenberg,D.Dooijes,R.J.E.Jongbloed,M.Michels,P.G.Postema,D.Majoor-
Krakauer,A.vandenWijngaard,M.M.A.M.Mannens,J.P.vanTintelen,I.M.vanLangenand
A.A.M.Wilde
(NetherlandsHeartJournal5-2010)
6.1 Introduction....................................................................................... 38
6.2 GeneticsofHCM .................................................................................. 38
6.3 FoundermutationsintheNetherlands........................................................... 38
6.4 Acknowledgements............................................................................... 40
References ........................................................................................ 40
7 RecurrentandfoundermutationsintheNetherlands:cardiacTroponinI(TNNI3) 43
genemutationsasacauseofsevereformsofhypertrophicandrestrictivecardio-
myopathy........................................................................................
A.vandenWijngaard,P.Volders,J.P.VanTintelen,J.D.H.Jongbloed,M.P.vandenBerg,
R.H.LekanneDeprez,M.M.A.M.Mannens,N.Hofmann,M.Slegtenhorst,D.Dooijes,M.Michels,
Y.Arens,R.JongbloedandB.J.M.Smeets
(NetherlandsHeartJournal8-2011)
7.1 Introduction....................................................................................... 44
7.2 Methods........................................................................................... 44
7.3 Results ............................................................................................ 45
7.4 Discussion......................................................................................... 48
7.5 Conclusion ........................................................................................ 49
7.6 Acknowledgements............................................................................... 49
References ........................................................................................ 49
8 RecurrentandfoundermutationsintheNetherlands:mutationp.K217delintropo- 51
ninT2,causingdilatedcardiomyopathy ....................................................
E.Otten,R.H.LekanneditDeprez,M.M.Weiss,M.vanSlegtenhorst,M.Joosten,J.J.vanderSmagt,
N.deJonge,W.S.Kerstjens-Frederikse,M.T.R.Roofthooft,A.H.M.M.Balk,M.P.vandenBerg,
J.S.RuiterandJ.P.vanTintelen
(NetherlandsHeartJournal10-2010)
8.1 Introduction....................................................................................... 52
8.2 MaterialsandMethods ........................................................................... 52
8.3 Results ............................................................................................ 52
8.4 Discussion......................................................................................... 54
8.5 Conclusion ........................................................................................ 56
8.6 Acknowledgement................................................................................ 56
References ........................................................................................ 56
9 RecurrentandfoundermutationsintheNetherlands:thecardiacphenotypeofDES 59
foundermutationsp.S13Fandp.N342D ....................................................
K.Y.vanSpaendonck-Zwarts,A.J.vanderKooi,M.P.vandenBerg,E.F.Ippel,L.G.Boven,
W.-C.Yee,A.vandenWijngaard,E.Brusse,J.E.Hoogendijk,P.A.Doevendans,M.deVisser,
J.D.H.JongbloedandJ.P.vanTintelen
(NetherlandsHeartJournal5-2012)
9.1 Introduction....................................................................................... 60
9.2 Methods........................................................................................... 60
9.3 Results ............................................................................................ 60
9.4 Discussion......................................................................................... 64
9.5 Acknowledgements............................................................................... 68
References ........................................................................................ 68
IX
TableofContents
10 RecurrentandfoundermutationsintheNetherlands:Plakophilin-2p.Arg79Xmuta- 69
tioncausingarrhythmogenicrightventricularcardiomyopathy/dysplasia............
P.A.vanderZwaag,M.G.P.J.Cox,C.vanderWerf,A.C.P.Wiesfeld,J.D.H.Jongbloed,D.Dooijes,
H.Bikker,R.Jongbloed,A.J.H.Suurmeijer,M.P.vandenBerg,R.M.W.Hofstra,R.N.W.Hauer,
A.A.M.WildeandJ.P.vanTintelen
(NetherlandsHeartJournal12-2010)
10.1 Introduction....................................................................................... 70
10.2 PatientsandMethods............................................................................. 70
10.3 Results ............................................................................................ 71
10.4 Discussion......................................................................................... 72
10.5 Conclusions ....................................................................................... 78
10.6 Acknowledgements............................................................................... 78
References ........................................................................................ 78
11 RecurrentandfoundermutationsintheNetherlands–Phospholambanp.Arg14del 81
mutationcausesarrhythmogeniccardiomyopathy .......................................
P.A.vanderZwaag,I.A.W.vanRijsingen,R.deRuiter,E.A.Nannenberg,J.A.Groeneweg,J.G.Post,
R.N.W.Hauer,I.C.vanGelder,M.P.vandenBerg,P.vanderHarst,A.A.M.WildeandJ.P.van
Tintelen
(NetherlandsHeartJournal5-2013)
11.1 Introduction....................................................................................... 82
11.2 Materials&methods.............................................................................. 82
11.3 Results ............................................................................................ 84
11.4 Discussion......................................................................................... 85
11.5 Acknowledgments ................................................................................ 86
References ........................................................................................ 87
12 RecurrentandfoundermutationsintheNetherlands:Extensiveclinicalvariabilityin 89
Marfansyndromepatientswithasinglenovelrecurrentfibrillin-1missensemuta-
tion ...............................................................................................
J.J.J.Aalberts,A.G.Schuurman,G.Pals,B.J.C.Hamel,G.Bosman,Y.Hilhorst-Hofstee,
D.Q.C.M.Barge-Schaapveld,B.J.M.Mulder,M.P.vandenBergandJ.P.vanTintelen
(NetherlandsHeartJournal2-2010)
12.1 Introduction....................................................................................... 90
12.2 Patientsandmethods............................................................................. 90
12.3 Results ............................................................................................ 90
12.4 Discussion......................................................................................... 92
12.5 Conclusion ........................................................................................ 93
12.6 Acknowledgements............................................................................... 93
References ........................................................................................ 93
13 FoundermutationsintheNetherlands:geographicaldistributionofthemostpre- 95
valentmutationsinthelow-densitylipoproteinreceptorandapolipoproteinB
genes.............................................................................................
D.M.Kusters,R.Huijgen,J.C.Defesche,M.N.Vissers,I.Kindt,B.A.HuttenandJ.J.P.Kastelein
(NetherlandsHeartJournal4-2011)
13.1 Introduction....................................................................................... 96
13.2 PatientsandMethods............................................................................. 96
13.3 Results ............................................................................................ 96
13.4 Discussion......................................................................................... 100
13.5 Conclusion ........................................................................................ 101
13.6 Acknowledgements............................................................................... 102
References ........................................................................................ 102
11
11
Introduction
ArthurWildeandPeter vanTintelen