A Chinese pedigree with glucocorticoid remediable ... - Nature

Glucocorticoid-remediable aldosteronism (GRA) is an autosomal-dominant inherited aldosteronism that is often accompanied by early-onset ... Skiptomaincontent Thankyouforvisitingnature.com.YouareusingabrowserversionwithlimitedsupportforCSS.Toobtain thebestexperience,werecommendyouuseamoreuptodatebrowser(orturnoffcompatibilitymodein InternetExplorer).Inthemeantime,toensurecontinuedsupport,wearedisplayingthesitewithoutstyles andJavaScript. Advertisement nature hypertensionresearch articles article AbstractGlucocorticoid-remediablealdosteronism(GRA)isanautosomal-dominantinheritedaldosteronismthatisoftenaccompaniedbyearly-onsethypertension.GRAiscausedbytheunequalcrossoverofthe11β-hydroxylase(CYP11B1)andaldosteronesynthase(CYP11B2)genes.Asaresultofchimericgeneduplication,aldosteroneisectopicallysynthesizedintheadrenalzonafasciculataunderthecontrolofadrenocorticotropichormone(ACTH).Here,wedescribeaChinesepedigreewiththreeaffectedsubjects.Boththeuncleandnephewwerehospitalizedinourhospitalduetoearly-onsethypertension(onset<20yearsold)andwerediagnosedwithprimaryaldosteronism(PA).Theirlaboratorytestresultsrevealedhyperaldosteronism,hyporeninemia,ahighplasmaaldosteronetorenin(ARR)ratio,andnormalserumpotassium(K+).Captoprilfailedtosuppressaldosteronesecretion.Thisfamilyhadastrongpaternalhistoryofhypertension.Thirteenmembersunderwentgenetesting,andthreeofthemwerefoundtobeGRApositive.Throughlong-extensionPCR(XL-PCR)anddirectsequencing,weidentifiedtheCYP11B1/CYP11B2chimericgene,andwithunequalcrossoverbreakpointslocatedbetweenintron2ofCYP11B1andexon3ofCYP11B2inthethreepatients.Low-dosedexamethasonewaseffective.ThisisthefirstfamilyreportofGRAinnorthernChina.Moreover,acaseofGRAcombinedwithaCACNA1Hgenemutationisreportedforthefirsttime.Wefoundthatdihydropyridinecalciumchannelblockers(CCBs)combinedwithaldosteronereceptorantagonistsexertedgoodtherapeuticeffectsincontrollingbloodpressureinGRApatientsforwhomglucocorticoidtherapywasnotanoption. 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Additionalaccessoptions: Login Learnaboutinstitutionalsubscriptions Fig.1Fig.2Fig.3 ReferencesPizzoloF,TrabettiE,GuariniP,MulateroP,CiacciarelliA,BlengioGS,etal.Glucocorticoidremediablealdosteronism(GRA)screeninginhypertensivepatientsfromaprimarycaresetting.JHumHypertens.2005;19:325–327.CAS  Article  GoogleScholar  SutherlandDJ,RuseJL,LaidlawJC.Hypertension,increasedaldosteronesecretionandlowplasmareninactivityrelievedbydexamethasone.CanMedAssocJ.1966;95:1109–1119.CAS  PubMed  PubMedCentral  GoogleScholar  LitchfieldWR,AndersonBF,WeissRJ,LiftonRP,DluhyRG.Intracranialaneurysmandhemorrhagicstrokeinglucocorticoid-remediablealdosteronism.Hypertension1998;31:445–450.1Pt2CAS  Article  GoogleScholar  LiftonRP,DluhyRG,PowersM,RichGM,GutkinM,FalloF,etal.Hereditaryhypertensioncausedbychimaericgeneduplicationsandectopicexpressionofaldosteronesynthase.NatGenet.1992;2:66–74.CAS  Article  GoogleScholar  JonssonJR,KlemmSA,TunnyTJ,StowasserM,GordonRD.AnewgenetictestforfamilialhyperaldosteronismtypeIaidsinthedetectionofcurablehypertension.BiochemBiophysResCommun.1995;207:565–571.CAS  Article  GoogleScholar  MacConnachieAA,KellyKF,McNamaraA,LoughlinS,GatesLJ,InglisGC,etal.Rapiddiagnosisandidentificationofcross-oversitesinpatientswithglucocorticoidremediablealdosteronism.JClinEndocrinolMetab.1998;83:4328–4331.CAS  Article  GoogleScholar  CarvajalCA,StehrCB,GonzálezPA,RiquelmeEM,MonteroT,SantosMJ,etal.Adenovounequalcross-overmutationbetweenCYP11B1andCYP11B2genescausesfamilialhyperaldosteronismtypeI.JEndocrinolInvestig.2011;34:140–144.CAS  Article  GoogleScholar  MyersS,FreemanC,AutonA,DonnellyP,McVeanG.Acommonsequencemotifassociatedwithrecombinationhotspotsandgenomeinstabilityinhumans.NatGenet.2008;40:1124–1129.CAS  Article  GoogleScholar  SeidelE,ScheweJ,SchollUI.Geneticcausesofprimaryaldosteronism.ExpMolMed.2019;51:1–12.CAS  Article  GoogleScholar  DluhyRG,AndersonB,HarlinB,IngelfingerJ,LiftonR.Glucocorticoid-remediablealdosteronismisassociatedwithseverehypertensioninearlychildhood.JPediatr.2001;138:715–720.CAS  Article  GoogleScholar  MulateroP,diCellaSM,WilliamsTA,MilanA,MengozziG,ChiandussiL,etal.Glucocorticoidremediablealdosteronism:lowmorbidityandmortalityinafour-generationItalianpedigree.JClinEndocrinolMetab.2002;87:3187–3191.CAS  Article  GoogleScholar  DluhyRG,LiftonRP.Glucocorticoid-remediablealdosteronism(GRA):diagnosis,variabilityofphenotypeandregulationofpotassiumhomeostasis.Steroids.1995;60:48–51.CAS  Article  GoogleScholar  JamiesonA,SlutskerL,InglisGC,FraserR,WhitePC,ConnellJM.Glucocorticoid-suppressiblehyperaldosteronism:effectsofcrossoversiteandparentaloriginofchimaericgeneonphenotypicexpression.ClinSci.1995;88:563–570.CAS  Article  GoogleScholar  RichGM,UlickS,CookS,WangJZ,LiftonRP,DluhyRG.Glucocorticoid-remediablealdosteronisminalargekindred:clinicalspectrumanddiagnosisusingacharacteristicbiochemicalphenotype.AnnInternMed.1992;116:813–820.CAS  Article  GoogleScholar  MulateroP,VeglioF,PilonC,RabbiaF,ZocchiC,LimoneP,etal.Diagnosisofglucocorticoid-remediablealdosteronisminprimaryaldosteronism:aldosteroneresponsetodexamethasoneandlongpolymerasechainreactionforchimericgene.JClinEndocrinolMetab.1998;83:2573–2575.CAS  Article  GoogleScholar  McMahonGT,DluhyRG.Glucocorticoid-remediablealdosteronism.CardiolRev.2004;12:44–48.Article  GoogleScholar  LitchfieldWR,NewMI,CoolidgeC,LiftonRP,DluhyRG.Evaluationofthedexamethasonesuppressiontestforthediagnosisofglucocorticoid-remediablealdosteronism.JClinEndocrinolMetab.1997;82:3570–3573.CAS  PubMed  GoogleScholar  DownloadreferencesAcknowledgementsThisworkwassupportedbytheNationalKeyR&DProgramofChina(ProjectID.2018YFC1312703fromJC),CAMSInnovationFundforMedicalSciences(2016-I2M-1-006fromJC),NationalNaturalScienceFoundationofChina(ProjectID.81630014and81825002fromJC,ProjectID81700374fromLJ),BeijingOutstandingYoungScientistProgram(ProjectID.BJJWZYJH01201910023029,fromJC)andtheFundamentalResearchFundsfortheCentralUniversities(ProjectID.3332018055,fromXL).AuthorinformationAuthorsandAffiliationsDepartmentofHypertension,FuwaiHospital,StateKeyLaboratoryofCardiovascularDisease,NationalCenterforCardiovascularDiseases,ChineseAcademyofMedicalSciencesandPekingUnionMedicalCollege,Beijing,ChinaXiaoningLiu, HuiminZhang, WenjunMa, LeiSong, XianliangZhou & JunCaiCenterofBasicMedicalResearch,InstituteofMedicalInnovationandResearch,PekingUniversityThirdHospital,Beijing,ChinaLingJinAuthorsXiaoningLiuViewauthorpublicationsYoucanalsosearchforthisauthorin PubMed GoogleScholarLingJinViewauthorpublicationsYoucanalsosearchforthisauthorin PubMed GoogleScholarHuiminZhangViewauthorpublicationsYoucanalsosearchforthisauthorin PubMed GoogleScholarWenjunMaViewauthorpublicationsYoucanalsosearchforthisauthorin PubMed GoogleScholarLeiSongViewauthorpublicationsYoucanalsosearchforthisauthorin PubMed GoogleScholarXianliangZhouViewauthorpublicationsYoucanalsosearchforthisauthorin PubMed GoogleScholarJunCaiViewauthorpublicationsYoucanalsosearchforthisauthorin PubMed GoogleScholarCorrespondingauthorCorrespondenceto JunCai.Ethicsdeclarations Conflictofinterest Theauthorsdeclarenocompetinginterests. AdditionalinformationPublisher’snoteSpringerNatureremainsneutralwithregardtojurisdictionalclaimsinpublishedmapsandinstitutionalaffiliations.RightsandpermissionsReprintsandPermissionsAboutthisarticleCitethisarticleLiu,X.,Jin,L.,Zhang,H.etal.AChinesepedigreewithglucocorticoidremediablealdosteronism. HypertensRes44,1428–1433(2021).https://doi.org/10.1038/s41440-021-00685-3DownloadcitationReceived:11December2020Revised:27April2021Accepted:07May2021Published:30August2021IssueDate:November2021DOI:https://doi.org/10.1038/s41440-021-00685-3SharethisarticleAnyoneyousharethefollowinglinkwithwillbeabletoreadthiscontent:GetshareablelinkSorry,ashareablelinkisnotcurrentlyavailableforthisarticle.Copytoclipboard ProvidedbytheSpringerNatureSharedItcontent-sharinginitiative KeywordsGlucocorticoid-remediablealdosteronismPedigree CYP11B1/CYP11B2chimericgeneEarly-onsethypertension Accessthroughyourinstitution Changeinstitution Buyorsubscribe Advertisement Explorecontent Researcharticles Reviews&Analysis News&Comment Currentissue Collections Subscribe Signupforalerts RSSfeed Aboutthejournal JournalInformation Openaccesspublishing GuidetoAuthors AbouttheEditors CallforPaper Contact AboutthePartner ForAdvertisers Subscribe Publishwithus ForAuthors&Referees Submitmanuscript Search Searcharticlesbysubject,keywordorauthor Showresultsfrom Alljournals Thisjournal Search Advancedsearch Quicklinks Explorearticlesbysubject Findajob Guidetoauthors Editorialpolicies