OMIMOnlineMendelianInheritanceinManAll DatabasesPubMedNucleotideProteinGenomeStructurePMCTaxonomyOMIM SearchPubMedProteinNucleotideCoreNucleotideGSSESTStructureGenomeBooksCancerChromosomesConservedDomainsdbGaP3DDomainsGeneGenomeProjectGENSATGEOProfilesGEODataSetsHomoloGeneJournalsMeSHNCBIWebSiteNLMCatalogOMIAOMIMPMCPopSetProbeProteinClustersPubChemBioAssayPubChemCompoundPubChemSubstanceSNPTaxonomyToolKitUniGeneUniSTSLimitsPreview/IndexHistoryClipboardDetailsDisplayTitlesDetailedClinicalSynopsisAllelicVariantsASN1XMLLinkOutRelatedEntriesBookLinksGeneLinksGenomeLinksGEOProfileLinksHomoloGeneLinksNucleotideLinksOMIALinksPubChemBioAssayLinksPMCLinksProteinLinksPubMed(calculated)LinksPubMed(cited)LinksSNPLinksGeneGenotypeLinksStructureLinksUniGeneLinksUniSTSLinksShow5102050100200500SendtoTextFilePrinterClipboardAll1OMIMdbSNP0OMIMUniSTS0*238310GeneTestsLinksAMINOMETHYLTRANSFERASEAMTAlternativetitlessymbolsGLYCINECLEAVAGESYSTEMTPROTEINGCSTGenemaplocus3p212p211TEXTDESCRIPTIONTheenzymesystemforcleavageofglycine(glycinecleavagesystemEC21210)whichisconfinedtothemitochondriaiscomposedof4proteincomponentsPprotein(apyridoxalphosphatedependentglycinedecarboxylase238300)Hprotein(alipoicacidcontainingprotein238330)Tprotein(atetrahydrofolaterequiringenzyme)andLprotein(alipoamidedehydrogenase238331)Glycineencephalopathy(GCE605899)maybeduetoadefectinanyoneoftheseenzymesCLONINGTheTproteinoftheglycinecleavagesystemisalsoknownasaminomethyltransferase(AMT)Nanaoetal(1994)isolatedtheAMTgenefromahumanplacentacosmidlibraryTheyfoundthatthegeneisabout6kblongandcontains9exonsTheyidentified2putativeglucocorticoidresponsiveelementsandaputativethyroidhormoneresponsiveelementBydotblotanalysisKureetal(2001)detectedexpressionofAMTinalltissuestestedexceptstomachandbonemarrowGENEFUNCTIONSakataetal(2001)reportedthestructureandexpressionoftheglycinecleavagesysteminratcentralnervoussystemMAPPINGByfluorescenceinsituhybridizationNanaoetal(1994)assignedtheAMTgeneto3p212p211MOLECULARGENETICSInpatientswithglycineencephalopathyNanaoetal(1994)identifiedmutationsintheAMTgene(23831000012383100002)Tooneetal(2000)studied14unrelatedpatientswithglycineencephalopathyandidentifiedmutationsin4casesIn2patientsmutationswereidentifiedintheTprotein1patientwashomozygousforanarg320tohismutation(R320H2383100006)andtheotherpatientwasheterozygousforanovelglutaminetoterminationsubstitutionatcodon192(2383100007)ApplegarthandToone(2001)reviewedthelaboratorydiagnosisofglycineencephalopathyandconfirmed9mutationsintheTproteinand8mutationsinthePproteinTheyalsoreviewedthe7casesoftransientNKHknownatthattime(selectedexamples)0001GLYCINEENCEPHALOPATHY[AMTGLY269ASP]Nanaoetal(1994)foundthatapatientwithtypicalglycineencephalopathy(605899)washomozygousforamissensemutationintheAMTgeneaGtoAtransitionleadingtoaglytoaspsubstitutionataminoacid269(G269D)0002GLYCINEENCEPHALOPATHY[AMTGLY47ARG]In2sisterswithatypicalglycineencephalopathy(605899)Nanaoetal(1994)foundcompoundheterozygosityfor2missensemutationsintheTproteingeneaGtoAtransitionleadingtoaglytoargsubstitutionataminoacid47(G47R)in1alleleandaGtoAtransitionleadingtoanargtohissubstitutionataminoacid320(R320H2383100006)intheotheralleleNanaoetal(1994)pointedoutthatgly269whichwasmutantinthetypicallyseverecasetheystudied(see2383000001)isconservedinTproteinsofvariousspecieseveninEcoliwhereasgly47andarg320whichweremutantintheatypicalandmildercasesarereplacedbyalaandleurespectivelyinEcoliThusmutationoccurringinmoreconservativeaminoacidresiduesresultsinmoredeleteriousdamagetotheTproteinandamoresevereclinicalphenotype0003GLYCINEENCEPHALOPATHY[AMTHIS42ARG]Kureetal(1998)reportedalargeIsraeliArabkindredwithglycineencephalopathy(605899)EnzymaticanalysisdemonstratedthatTproteinactivitywasdeficientintheliverfrom1affectedpersoninthefamilyMutationdetectionrevealedamissensemutationinexon2resultinginanaminoacidsubstitutionfromhistidinetoarginineatposition42(his42toarg)HomozygosityfortheH42Rmutationwasseeninallaffectedmembersofthefamily0004GLYCINEENCEPHALOPATHY[AMT1BPDEL183C]InaJapanesepatientwithglycineencephalopathy(605899)Kureetal(1998)describeda1bpdeletion(183delC)andamissensemutationasp276tohis(2383100005)0005GLYCINEENCEPHALOPATHY[AMTASP276HIS]InaJapanesepatientwithglycineencephalopathy(605899)ofneonatalonsetKureetal(1998)foundaGtoCsubstitutionatposition955inexon7resultinginanaminoacidchangefromaspartatetohistidineatposition2760006GLYCINEENCEPHALOPATHY[AMTARG320HIS]See2383100001andNanaoetal(1994)Tooneetal(2001)screenedaDNAbankfrom50patientswithenzymaticallyconfirmedNKHandidentifiedthearg320tohis(R320H)mutationin7%ofalleles0007GLYCINEENCEPHALOPATHY[AMTGLN192TER]InapatientwithneonatalonsetNKH(605899)Tooneetal(2000)identifiedaCtoTtransitionresultinginaglutaminetoterminationcodonsubstitutionatresidue192(Q192X)Theothermutationinthispatientwasnotidentified0008GLYCINEENCEPHALOPATHY[AMTIVS7GA1]Tooneetal(2001)reportedanovelsplicesitemutationatthe1positionofintron7oftheAMTgeneGwasconvertedtoAThismutationwasfoundin3unrelatedfamiliesandwasnotfoundinanynormalcontrolsSEEALSOHayasakaetal(1983)Tooneetal(2000)REFERENCES1ApplegarthDATooneJRNonketotichyperglycinemia(glycineencephalopathy)laboratorydiagnosisMolecGenetMetab7413914620012HayasakaKTadaKKikuchiGWinterSNyhanWLNonketotichyperglycinemiatwopatientswithprimarydefectsofPproteinandTproteinrespectivelyintheglycinecleavagesystemPediatRes179679701983PubMedID63365993KureSKojimaKKudoTKannoKAokiYSuzukiYShinkaTSakataYNarisawaKMatsubaraYChromosomallocalizationstructuresinglenucleotidepolymorphismsandexpressionofthehumanHproteingeneoftheglycinecleavagesystem(GCSH)acandidategenefornonketotichyperglycinemiaJHumGenet463783842001PubMedID114508474KureSMandelHRollandMOSakataYShinkaTDruganABonehATadaKMatsubaraYNarisawaKAmissensemutation(his42arg)intheTproteingenefromalargeIsraeliArabkindredwithnonketotichyperglycinemiaHumGenet1024304341998PubMedID96002395KureSShinkaTSakataYOsamuNTakayanagiMTadaKMatsubaraYNarisawaKAonebasedeletion(183delC)andamissensemutation(D276H)intheTproteingenefromaJapanesefamilywithnonketotichyperglycinemiaJHumGenet431351371998PubMedID96215206NanaoKOkamuraIkedaKMotokawaYDanksDMBaumgartnerERTakadaGHayasakaKIdentificationofthemutationsintheTproteingenecausingtypicalandatypicalnonketotichyperglycinemiaHumGenet936556581994PubMedID80055897NanaoKTakadaGTakahashiESekiNKomatsuYOkamuraIkedaKMotokawaYHayasakaKStructureandchromosomallocalizationoftheaminomethyltransferasegene(AMT)Genomics1927301994PubMedID81882358SakataYOwadaYSatoKKojimaKHisanagaKShinkaTSuzukiYAokiYSatohJKondoHMatsubaraYKureSStructureandexpressionoftheglycinecleavagesysteminratcentralnervoussystemMolecBrainRes941191302001PubMedID115977729TooneJRApplegarthDACoulterMackieMBJamesERIdentificationofthefirstreportedsplicesitemutation(IVS71GA)intheaminomethyltransferase(Tprotein)gene(AMT)oftheglycinecleavagecomplexin3unrelatedfamilieswithnonketotichyperglycinemia(Abstract)HumMutat1776only200010TooneJRApplegarthDACoulterMackieMBJamesERRecurrentmutationsinPandTproteinsoftheglycinecleavagecomplexandanovelTproteinmutation(N145I)astrategyforthemolecularinvestigationofpatientswithnonketotichyperglycinemia(NKH)MolecGenetMetab72322325200111TooneJRApplegarthDACoulterMackieMBJamesERBiochemicalandmolecularinvestigationsofpatientswithnonketotichyperglycemiaMolecGenetMetab701161212000CONTRIBUTORSAdaHamoshupdated2/20/2002VictorAMcKusickupdated8/10/2001AdaHamoshupdated5/2/2001ClairAFrancomanoupdated6/16/1998ClairAFrancomanoupdated5/26/1998BeatSteinmannupdated1/17/1997CREATIONDATEVictorAMcKusick6/3/1986EDITHISTORYterry3/11/2002alopez2/25/2002terry2/20/2002mcapotos8/10/2001carol6/22/2001carol5/3/2001carol5/2/2001carol4/17/2000carol4/6/2000carol4/4/2000carol7/16/1998carol6/19/1998terry6/16/1998carol5/30/1998carol5/26/1998dholmes5/21/1998joanna1/17/1997joanna1/17/1997mimadm2/19/1994carol2/7/1994carol8/17/1992supermim3/16/1992supermim3/20/1990carol12/21/1989Copyright©19662007JohnsHopkinsUniversityDisplayTitlesDetailedClinicalSynopsisAllelicVariantsASN1XMLLinkOutRelatedEntriesBookLinksGeneLinksGenomeLinksGEOProfileLinksHomoloGeneLinksNucleotideLinksOMIALinksPubChemBioAssayLinksPMCLinksProteinLinksPubMed(calculated)LinksPubMed(cited)LinksSNPLinksGeneGenotypeLinksStructureLinksUniGeneLinksUniSTSLinksShow5102050100200500SendtoTextFilePrinterClipboardDisclaimerWritetotheHelpDeskPrivacyPolicyNCBINLMNIH