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The lysosomal storage disorders mucolipidosis type II, type III alpha/beta, and type III gamma: update on GNPTAB and GNPTG mutations

2019-04-13Journal article Restricted access
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dc.contributor.authorVelho, Renata Voltolini
dc.contributor.authorHarms, Frederike L.
dc.contributor.authorDanyukova, Tatyana
dc.contributor.authorLudwig, Nataniel F.
dc.contributor.authorFriez, Michael J.
dc.contributor.authorCathey, Sara S.
dc.contributor.authorFilocamo, Mirella
dc.contributor.authorTappino, Barbara
dc.contributor.authorGüneş, Nilay
dc.contributor.authorTüysüz, Beyhan
dc.contributor.authorTylee, Karen L.
dc.contributor.authorBrammeier, Kathryn L.
dc.contributor.authorHeptinstall, Lesley
dc.contributor.authorOussoren, Esmee
dc.contributor.authorPloeg, Ans T.
dc.contributor.authorPetersen, Christine
dc.contributor.authorAlves, Sandra
dc.contributor.authorSaavedra, Gloria Durán
dc.contributor.authorSchwartz, Ida V.
dc.contributor.authorMuschol, Nicole
dc.contributor.authorKutsche, Kerstin
dc.contributor.authorPohl, Sandra
dc.date.accessioned2020-05-06T16:29:52Z
dc.date.available2020-05-06T16:29:52Z
dc.date.issued2019-04-13
dc.description.abstractMutations in the GNPTAB and GNPTG genes cause mucolipidosis (ML) type II, type III alpha/beta, and type III gamma, which are autosomal recessively inherited lysosomal storage disorders. GNPTAB and GNPTG encode the α/β-precursor and the γ-subunit of N-acetylglucosamine (GlcNAc)-1-phosphotransferase, respectively, the key enzyme for the generation of mannose 6-phosphate targeting signals on lysosomal enzymes. Defective GlcNAc-1-phosphotransferase results in missorting of lysosomal enzymes and accumulation of non-degradable macromolecules in lysosomes, strongly impairing cellular function. MLII-affected patients have coarse facial features, cessation of statural growth and neuromotor development, severe skeletal abnormalities, organomegaly, and cardiorespiratory insufficiency leading to death in early childhood. MLIII alpha/beta and MLIII gamma are attenuated forms of the disease. Since the identification of the GNPTAB and GNPTG genes, 564 individuals affected by MLII or MLIII have been described in the literature. In this report, we provide an overview on 258 and 50 mutations in GNPTAB and GNPTG, respectively, including 58 novel GNPTAB and seven novel GNPTG variants. Comprehensive functional studies of GNPTAB missense mutations did not only gain insights into the composition and function of the GlcNAc-1-phosphotransferase, but also helped to define genotype-phenotype correlations to predict the clinical outcome in patients.pt_PT
dc.description.sponsorshipBrazilian National Council for Scientific and Technological Development/International; 125440785-SFB877/Deutsche Forschungsgemeinschaft/International; PO 1539/1-1/Deutsche Forschungsgemeinschaft/International; 395238399-PO 1539/1-1/Deutsche Forschungsgemeinschaft/International; KU 1240/10-1/Deutsche Forschungsgemeinschaft/International; Cinque per mille e Ricerca Corrente, Ministero della Salute/International.pt_PT
dc.description.sponsorshipThis study was funded by Deutsche Forschungsgemeinschaft (DFG, German Research Foundation, 125440785‐ SFB877, 395238399‐PO 1539/1‐1 to S. P. and 1240/10‐1 to K. K.), the Brazilian National Council for Scientific and Technological Development (CNPq) to N. F. L. and by unrestricted grants from Cinque per mille e Ricerca Corrente, Ministero della Salute to M. F. and B. T.
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationHum Mutat. 2019 Jul;40(7):842-864. doi: 10.1002/humu.23748. Epub 2019 Apr 13pt_PT
dc.identifier.doi10.1002/humu.23748pt_PT
dc.identifier.issn1059-7794
dc.identifier.urihttp://hdl.handle.net/10400.18/6606
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherWileypt_PT
dc.relation.publisherversionhttps://onlinelibrary.wiley.com/doi/epdf/10.1002/humu.23748pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/pt_PT
dc.subjectExonspt_PT
dc.subjectHumanspt_PT
dc.subjectIntronspt_PT
dc.subjectLysosomal Storage Diseases, Nervous Systempt_PT
dc.subjectMucolipidosespt_PT
dc.subjectPhenotypept_PT
dc.subjectPrognosispt_PT
dc.subjectProtein Domainspt_PT
dc.subjectTransferases (Other Substituted Phosphate Groups)pt_PT
dc.subjectMutationpt_PT
dc.subjectDoenças Genéticaspt_PT
dc.titleThe lysosomal storage disorders mucolipidosis type II, type III alpha/beta, and type III gamma: update on GNPTAB and GNPTG mutationspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage864pt_PT
oaire.citation.issue7pt_PT
oaire.citation.startPage842pt_PT
oaire.citation.titleHuman Mutationpt_PT
oaire.citation.volume40pt_PT
rcaap.embargofctDe acordo com política editorial da revista.pt_PT
rcaap.rightsembargoedAccesspt_PT
rcaap.typearticlept_PT

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