OMIMOnlineMendelianInheritanceinManAll DatabasesPubMedNucleotideProteinGenomeStructurePMCTaxonomyOMIM SearchPubMedProteinNucleotideCoreNucleotideGSSESTStructureGenomeBooksCancerChromosomesConservedDomainsdbGaP3DDomainsGeneGenomeProjectGENSATGEOProfilesGEODataSetsHomoloGeneJournalsMeSHNCBIWebSiteNLMCatalogOMIAOMIMPMCPopSetProbeProteinClustersPubChemBioAssayPubChemCompoundPubChemSubstanceSNPTaxonomyToolKitUniGeneUniSTSLimitsPreview/IndexHistoryClipboardDetailsDisplayTitlesDetailedClinicalSynopsisAllelicVariantsASN1XMLLinkOutRelatedEntriesBookLinksGeneLinksGenomeLinksGEOProfileLinksHomoloGeneLinksNucleotideLinksOMIALinksPubChemBioAssayLinksPMCLinksProteinLinksPubMed(calculated)LinksPubMed(cited)LinksSNPLinksGeneGenotypeLinksStructureLinksUniGeneLinksUniSTSLinksShow5102050100200500SendtoTextFilePrinterClipboardAll1OMIMdbSNP1OMIMUniSTS0*604566GeneTestsLinksALG6SCEREVISIAEHOMOLOGOFAlternativetitlessymbolsALG6Genemaplocus1p223TEXTCongenitaldisordersofglycosylation(CDGs)arecausedbydefectsinmannoseadditionduringNlinkedoligosaccharideassemblyOnetypeofCDGCDGIc(603147)ischaracterizedbyanaccumulationofdolichylpyrophosphatelinkedMan(9)GlcNAc(2)withinthecellsofaffectedpatientsAnanalogousaccumulationoccursinyeastwithmutantALG5(604565)andALG6genesALG5codesfordolichylphosphateglucosyltransferasewhereasALG6codesforMan(9)GlcNAc(2)PPDolalpha13glucosyltransferaseUsingdegeneratePCRwithinregionsofyeastALG6thataredissimilartothecloselyrelatedyeastALG8(608103)toscreenahumanTcellcDNAlibraryImbachetal(1999)obtainedacompletecDNAencodingtheorthologofyeastALG6HumanALG6encodesa507aminoacidtransmembraneproteinthatis51%similartotheyeastproteinNorthernblotanalysisrevealedexpressionofa24kbALG6transcriptinpancreasplacentaliverheartbrainkidneyskeletalmuscleandlungByscreeninganESTdatabaseforfragmentsidenticaltoALG6Imbachetal(2000)mappedtheALG6geneto1p223Imbachetal(1999)showedthatall4ofthepatientstheyhaddescribedwithCDGIc(Burdaetal1998)hadthesamehomozygousala333tovalpointmutation(A333V6045660001)inthehumanorthologoftheScerevisiaegeneALG6ExpressionofthemutanthumangeneinayeastvectorresultedinahypoglycosylationphenotypeImbachetal(2000)identified7additionalcasesofCDGIcamongagroupof35CDGpatientsTheydeterminedtheorganizationoftheALG6generevealing14exonsthatspreadover55kbByPCRamplificationandsequencingofALG6exons3mutationsinadditiontothepreviouslydescribedA333VmutationweredetectedintheCDGIcpatientsThedetrimentaleffectofthesemutationsonALG6activitywasconfirmedbycomplementationofALG6yeastmutantsHaplotypeanalysisofCDGIcpatientsrevealedafoundereffectfortheALG6allelebearingtheA333VmutationAlthoughmorethan80%ofCDGpatientsfallintotypeIaCDGIcmaybethesecondmostcommonformofthediseaseA911TCtransitionintheALG6genepredictedtoleadtoaphe304tosersubstitution(6045660002)wasdescribedinrelationtoCDGIcbyImbachetal(2000)Westphaletal(2000)andHanefeldetal(2000)Howeverinthesestudieswhether911TCwasacommonpolymorphismoracausalmutationremainedunclearVuillaumierBarrotetal(2001)screenedforthe911TCsubstitutioninALG6in54unrelatedhealthyFrenchindividualsTheyfound23heterozygous(426%)and3homozygous(55%)individualsindicatingthat911TCisacommonpolymorphismwithanallelefrequencyof27%inaFrenchpopulationandnotacausalmutationofCDGIcWestphaletal(2002)showedthattheF304SalleleofALG6hadreducedabilitytorescuedefectiveglycosylationofanalg6deficientstrainofScerevisiaeduringrapidgrowthTheauthorsthengenotyped300controlsand100CDGpatientswithknownmutationsinPMM2(601785)orMPI(154550)atcodon304ofALG6TheF304SvariantallelefrequencywasidenticalinbothCDGpatientsandcontrolsHowevertheF304Sgenotypefrequencyin55CDGIapatientswassignificantlyhigherinseverelyaffectedpatientscomparedtomild/moderatelyaffectedpatientsSeverelyaffectedpatientswiththePMM2mutationsF119L(6017850006)andR141H(6017850001)carriedtheF304SmutationmoreoftenthanmildlyaffectedpatientsClinicalseverityofmildlyaffectedsibswiththesamePMM2mutationsdidnotcorrelatewithF304SgenotypeTheauthorsconcludedthatthepresenceoftheF304SallelemayexacerbatetheclinicaloutcomeinseverelyaffectedCDGpatients(selectedexamples)0001CONGENITALDISORDEROFGLYCOSYLATIONTYPEIc[ALG6ALA333VAL]In4unrelatedpatientswithCDGIc(603147)Imbachetal(1999)identifieda998CTtransitionthatledtoanala333toval(A333V)aminoacidsubstitutioninthehumanhomologoftheyeastALG6gene0002CONGENITALDISORDEROFGLYCOSYLATIONTYPEIc[ALG6PHE304SER]In2patientswithCDGIc(603147)Imbachetal(2000)identifieda911TCtransitionthatledtoaphe304toser(F304S)substitutioninthehumanhomologoftheyeastALG6geneREFERENCES1BurdaPBorsigLdeRijkAndelJWeversRJaekenJCarchonHBergerEGAebiMAnovelcarbohydratedeficientglycoproteinsyndromecharacterizedbyadeficiencyinglucosylationofthedolichollinkedoligosaccharideJClinInvest1026476521998PubMedID97104312HanefeldFKornerCHolzbachEberleUvonFiguraKCongenitaldisorderofglycosylationIccasereportandgeneticdefectNeuropediatrics3160622000PubMedID108325783ImbachTBurdaPKuhnertPWeversRAAebiMBergerEGHennetTAmutationinthehumanorthologoftheSaccharomycescerevisiaeALG6genecausescarbohydratedeficientglycoproteinsyndrometypeIcProcNatAcadSci96698269871999PubMedID103598254ImbachTGrunewaldSSchenkBBurdaPSchollenEWeversRAJaekenJdeKlerkJBCBergerEGMatthijsGAebiMHennetTMultiallelicoriginofcongenitaldisorderofglycosylation(CDG)IcHumGenet1065385452000PubMedID109146845VuillaumierBarrotSLeBizecCDurandGSetaNTheT911C(F304S)substitutioninthehumanALG6geneisacommonpolymorphismandnotacausalmutationofCDGIcJHumGenet465475482001PubMedID115589056WestphalVKjaergaardSSchollenEMartensKGrunewaldSSchwartzMMatthijsGFreezeHHAfrequentmildmutationinALG6mayexacerbatetheclinicalseverityofpatientswithcongenitaldisorderofglycosylationIa(CDGIa)causedbyphosphomannomutasedeficiencyHumMolecGenet115996042002PubMedID118750547WestphalVSchottstadtCMarquardtTFreezeHHAnalysisofmultiplemutationsinthehALG6geneinapatientwithcongenitaldisorderofglycosylationIcMolecGenetMetab702192232000CONTRIBUTORSGeorgeETillerupdated10/9/2002VictorAMcKusickupdated10/11/2001PaulJConverseupdated9/18/2000VictorAMcKusickupdated6/13/2000CREATIONDATEPaulJConverse2/18/2000EDITHISTORYcwells11/7/2003mgross9/18/2003cwells10/9/2002mcapotos10/26/2001mcapotos10/11/2001mgross9/18/2000mcapotos7/20/2000mcapotos6/29/2000terry6/13/2000carol2/18/2000Copyright©19662007JohnsHopkinsUniversityDisplayTitlesDetailedClinicalSynopsisAllelicVariantsASN1XMLLinkOutRelatedEntriesBookLinksGeneLinksGenomeLinksGEOProfileLinksHomoloGeneLinksNucleotideLinksOMIALinksPubChemBioAssayLinksPMCLinksProteinLinksPubMed(calculated)LinksPubMed(cited)LinksSNPLinksGeneGenotypeLinksStructureLinksUniGeneLinksUniSTSLinksShow5102050100200500SendtoTextFilePrinterClipboardDisclaimerWritetotheHelpDeskPrivacyPolicyNCBINLMNIH