{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:19:10Z","timestamp":1788135550948,"version":"build-2803163510"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":75,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Sociedade Portuguesa de Doen\u00e7as Metab\u00f3licas","award":["2020DGH1834"],"award-info":[{"award-number":["2020DGH1834"]}]},{"name":"Associate Laboratory for Animal and Veterinary Sciences","award":["AL4A-PROJ-LT3.5"],"award-info":[{"award-number":["AL4A-PROJ-LT3.5"]}]},{"name":"Deutsche Forschungsgesellschaft","award":["517063424"],"award-info":[{"award-number":["517063424"]}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["2022.13676.BD"],"award-info":[{"award-number":["2022.13676.BD"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Mucolipidosis type II (ML II) is a lysosomal storage disorder caused by deficiency of N-acetylglucosamine-1-phosphotransferase (GlcNAc-PT), which impairs the trafficking of lysosomal hydrolases. Of all ML II pathogenic variants, c.3503_3504del in\n                      <jats:italic>GNPTAB<\/jats:italic>\n                      exon 19 is the most prevalent, therefore constituting a compelling molecular target for the development of personalized therapeutic strategies. Here, we explored the feasibility of an innovative RNA based-therapeutic strategy using antisense oligonucleotides (ASOs) designed to induce exon 19 skipping in\n                      <jats:italic>GNPTAB<\/jats:italic>\n                      pre-mRNA. This approach was previously successfully tested at the mRNA level in fibroblasts from ML II patients, where it generated an in-frame mRNA. In the present study, our aim was to evaluate whether\n                      <jats:italic>GNPTAB<\/jats:italic>\n                      exon 19 skipping could increase GlcNAc-PT levels and consequently improve the cellular phenotype of ML II patients carrying this pathogenic variant. To address this, we designed a functional approach based on the overexpression of a\n                      <jats:italic>GNPTAB<\/jats:italic>\n                      construct carrying the exon 19 deletion enabling the indirect evaluation of the resulting protein\u00b4s functionality.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our first results demonstrated that in ML II fibroblasts, ASO treatment led to a modest increase in lysosomal hydrolase activity at 24\u00a0h and 48\u00a0h. Moreover, LAMP-1 expression remained elevated and comparable to untreated ML II cells, indicating that GlcNAc-PT activity was not restored. To further investigate the functional relevance of exon 19 skipping, overexpression studies were performed in HEK293T cells. Three constructs (pGNPTAB WT, pGNPTAB del_exon19 and pGNPTAB c.3503_3504del) were expressed. Both pGNPTAB WT and pGNPTAB del_exon19 constructs produced the \u03b1\/\u03b2-precursor. However, only the WT construct generated the mature \u03b2-subunit, whereas the pGNPTAB c.3503_3504del construct showed no detectable expression. These findings indicate that exon 19 is essential for proper GlcNAc-PT processing and enzymatic activity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Although ASO treatment corrected splicing at the mRNA level, it did not restore GlcNAc-PT activity in ML II patient cells. Nonetheless, our findings clarify the functional importance of exon 19 and demonstrate that overexpression of an exon-skipped construct provides a simple and effective strategy to indirectly assess protein functionality, supporting the prioritization of this kind of approach to test an exon-skipping ASO-based approach before advancing to studies in patient-derived cells.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13023-026-04430-2","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T12:33:12Z","timestamp":1781699592000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Relevance of functional studies for assessing an antisense oligonucleotide-mediated exon skipping therapeutic strategy for mucolipidosis type II"],"prefix":"10.1186","volume":"21","author":[{"given":"Mariana","family":"Gon\u00e7alves","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marisa","family":"Encarna\u00e7\u00e3o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciana","family":"Moreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo","family":"Gaspar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Joana","family":"Duarte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Francisca","family":"Coutinho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana In\u00eas","family":"Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Jo\u00e3o","family":"Prata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Omidi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naemi","family":"Euchner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Pohl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederico","family":"Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana","family":"Matos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8881-9197","authenticated-orcid":false,"given":"Sandra","family":"Alves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"4430_CR1","doi-asserted-by":"publisher","first-page":"2047","DOI":"10.1038\/s41436-021-01244-4","volume":"23","author":"EJ Dogterom","year":"2021","unstructured":"Dogterom EJ, Wagenmakers MAEM, Wilke M, Demirdas S, Muschol NM, Pohl S, et al. Mucolipidosis type II and type III: a systematic review of 843 published cases. Genetics in Medicine. Springer Nat. 2021;23:2047\u201356. https:\/\/doi.org\/10.1038\/s41436-021-01244-4.","journal-title":"Springer Nat"},{"key":"4430_CR2","doi-asserted-by":"publisher","first-page":"842","DOI":"10.1002\/humu.23748","volume":"40","author":"RV Velho","year":"2019","unstructured":"Velho RV, Harms FL, Danyukova T, Ludwig NF, Friez MJ, Cathey SS, et al. The lysosomal storage disorders mucolipidosis type II, type III alpha\/beta, and type III gamma: Update on GNPTAB and GNPTG mutations. Hum Mutat. 2019;40:842\u201364. https:\/\/doi.org\/10.1002\/humu.23748.","journal-title":"Hum Mutat"},{"key":"4430_CR3","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/j.tcb.2023.06.005","volume":"34","author":"T Braulke","year":"2024","unstructured":"Braulke T, Carette JE, Palm W. Lysosomal enzyme trafficking: from molecular mechanisms to human diseases. Trends Cell Biol Elsevier Ltd. 2024;34:198\u2013210. https:\/\/doi.org\/10.1016\/j.tcb.2023.06.005.","journal-title":"Trends Cell Biol Elsevier Ltd"},{"key":"4430_CR4","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1016\/j.ymgme.2011.12.012","volume":"105","author":"MF Coutinho","year":"2012","unstructured":"Coutinho MF, Prata MJ, Alves S. Mannose-6-phosphate pathway: A review on its role in lysosomal function and dysfunction. Mol Genet Metab Elsevier Inc. 2012;105:542\u201350. https:\/\/doi.org\/10.1016\/j.ymgme.2011.12.012.","journal-title":"Mol Genet Metab Elsevier Inc"},{"key":"4430_CR5","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1126\/science.1205677","volume":"333","author":"K Marschner","year":"2011","unstructured":"Marschner K, Kollmann K, Schweizer M, Braulke T, Pohl S. A Key Enzyme in the Biogenesis of Lysosomes Is a Protease That Regulates Cholesterol Metabolism. Sci (1979). 2011;333:87\u201390. https:\/\/doi.org\/10.1126\/science.1205677.","journal-title":"Sci (1979)"},{"key":"4430_CR6","doi-asserted-by":"publisher","unstructured":"Gorelik A, Illes K, Bui KH, Nagar B. Structures of the mannose-6-phosphate pathway enzyme, GlcNAc-1-phosphotransferase. Proceedings of the National Academy of Sciences. 2022;119. https:\/\/doi.org\/10.1073\/pnas.2203518119.","DOI":"10.1073\/pnas.2203518119"},{"key":"4430_CR7","doi-asserted-by":"publisher","unstructured":"Liu Q, Wang W, Xu L, Zhang Q, Wang H. The host mannose-6-phosphate pathway and viral infection. Front Cell Infect Microbiol Front Media SA. 2024:1349221. https:\/\/doi.org\/10.3389\/fcimb.2024.1349221.","DOI":"10.3389\/fcimb.2024.1349221"},{"key":"4430_CR8","doi-asserted-by":"publisher","first-page":"10246","DOI":"10.1073\/pnas.1308453110","volume":"110","author":"Y Qian","year":"2013","unstructured":"Qian Y, Flanagan-Steet H, Van Meel E, Steet R, Kornfeld SA. The DMAP interaction domain of UDP-GlcNAc: Lysosomal enzyme N-acetylglucosamine-1-phosphotransferase is a substrate recognition module. Proc Natl Acad Sci U S A. 2013;110:10246\u201351. https:\/\/doi.org\/10.1073\/pnas.1308453110.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"4430_CR9","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1089\/hum.2020.034","volume":"31","author":"L Matos","year":"2020","unstructured":"Matos L, Vilela R, Rocha M, Santos JI, Coutinho MF, Gaspar P, et al. Development of an Antisense Oligonucleotide-Mediated Exon Skipping Therapeutic Strategy for Mucolipidosis II: Validation at RNA Level. Hum Gene Ther. 2020;31:775\u201383. https:\/\/doi.org\/10.1089\/hum.2020.034.","journal-title":"Hum Gene Ther"},{"key":"4430_CR10","doi-asserted-by":"publisher","first-page":"1238","DOI":"10.1074\/jbc.M112.407676","volume":"288","author":"M Franke","year":"2013","unstructured":"Franke M, Braulke T, Storch S. Transport of the GlcNAc-1-phosphotransferase \u03b1\/\u03b2-Subunit Precursor Protein to the Golgi Apparatus Requires a Combinatorial Sorting Motif. J Biol Chem. 2013;288:1238\u201349. https:\/\/doi.org\/10.1074\/jbc.M112.407676.","journal-title":"J Biol Chem"},{"key":"4430_CR11","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1002\/humu.22502","volume":"35","author":"R De Pace","year":"2014","unstructured":"De Pace R, Coutinho MF, Koch-Nolte F, Haag F, Prata MJ, Alves S, et al. Mucolipidosis II-related mutations inhibit the exit from the endoplasmic reticulum and proteolytic cleavage of GlcNAc-1-phosphotransferase precursor protein (GNPTAB). Hum Mutat John Wiley Sons Inc. 2014;35:368\u201376. https:\/\/doi.org\/10.1002\/humu.22502.","journal-title":"Hum Mutat John Wiley Sons Inc"},{"key":"4430_CR12","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1146\/annurev-med-041217-010829","volume":"70","author":"CF Bennett","year":"2019","unstructured":"Bennett CF. Therapeutic antisense oligonucleotides are coming of age. Annu Rev Med. 2019;70:307\u201321. https:\/\/doi.org\/10.1146\/annurev-med-041217-010829.","journal-title":"Annu Rev Med"},{"key":"4430_CR13","doi-asserted-by":"publisher","first-page":"2270","DOI":"10.3390\/ijms26052270","volume":"26","author":"Y Takeshima","year":"2025","unstructured":"Takeshima Y. Expansion of Splice-Switching Therapy with Antisense Oligonucleotides. Int J Mol Sci Multidisciplinary Digit Publishing Inst (MDPI). 2025;26:2270. https:\/\/doi.org\/10.3390\/ijms26052270.","journal-title":"Int J Mol Sci Multidisciplinary Digit Publishing Inst (MDPI)"},{"key":"4430_CR14","doi-asserted-by":"publisher","unstructured":"N\u00fcchel J, Omidi M, Fernandes SA, Tauber M, Pohl S, Plomann M, et al. GRASP55 safeguards proper lysosome function by controlling sorting of lysosomal enzymes at the Golgi. Lindsay MA, Griffiths-Jones S, editors. Essays Biochem. 2024:79\u201390. https:\/\/doi.org\/10.1101\/2024.12.10.627846.","DOI":"10.1101\/2024.12.10.627846"},{"key":"4430_CR15","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1111\/j.1432-1033.1985.tb09058.x","volume":"150","author":"JM Aerts","year":"1985","unstructured":"Aerts JM, Donker-Koopman WE, van der Vliet MK, Jonsson LM, Ginns EI, Murray GJ, et al. The occurrence of two immunologically distinguishable beta-glucocerebrosidases in human spleen. Eur J Biochem. 1985;150:565\u201374. https:\/\/doi.org\/10.1111\/j.1432-1033.1985.tb09058.x.","journal-title":"Eur J Biochem"},{"key":"4430_CR16","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1016\/0009-8981(65)90148-8","volume":"12","author":"JW Woollen","year":"1965","unstructured":"Woollen JW, Walker PG. The fluorimetric estimation of \u03b2-glucuronidase in blood plasma. Clin Chim Acta. 1965;12:659\u201370. https:\/\/doi.org\/10.1016\/0009-8981(65)90148-8.","journal-title":"Clin Chim Acta"},{"key":"4430_CR17","doi-asserted-by":"publisher","first-page":"101313","DOI":"10.1016\/j.omtm.2024.101313","volume":"Elsevier BV","author":"S Crippa","year":"2024","unstructured":"Crippa S, Alberti G, Passerini L, Savoia EO, Mancino M, De Ponti G, et al. A GLB1 transgene with enhanced therapeutic potential for the preclinical development of ex-vivo gene therapy to treat mucopolysaccharidosis type IVB. Mol Ther Methods Clin Dev. 2024;Elsevier BV:101313. https:\/\/doi.org\/10.1016\/j.omtm.2024.101313.","journal-title":"Mol Ther Methods Clin Dev"},{"key":"4430_CR18","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/1471-2350-11-19","volume":"11","author":"P Gaspar","year":"2010","unstructured":"Gaspar P, Herrera J, Rodrigues D, Cerezo S, Delgado R, Andrade CF, et al. Frequency of Fabry disease in male and female haemodialysis patients in Spain. BMC Med Genet. 2010;11:19. https:\/\/doi.org\/10.1186\/1471-2350-11-19.","journal-title":"BMC Med Genet"},{"key":"4430_CR19","doi-asserted-by":"publisher","first-page":"3871","DOI":"10.3390\/ijms26083871","volume":"26","author":"ME Moutinho","year":"2025","unstructured":"Moutinho ME, Gon\u00e7alves M, Duarte AJ, Encarna\u00e7\u00e3o M, Coutinho MF, Matos L, et al. Establishment of a Human iPSC Line from Mucolipidosis Type II That Expresses the Key Markers of the Disease. Int J Mol Sci Multidisciplinary Digit Publishing Inst (MDPI). 2025;26:3871. https:\/\/doi.org\/10.3390\/ijms26083871.","journal-title":"Int J Mol Sci Multidisciplinary Digit Publishing Inst (MDPI)"},{"key":"4430_CR20","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1007\/BF01799940","volume":"14","author":"MG Ribeiro","year":"1991","unstructured":"Ribeiro MG, Pinto RA, Dos Santos MR, Maia M, S\u00e1 Miranda MC. Biochemical characterization of \u03b2-hexosaminidase in different biological specimens from eleven patients with GM2\u2010gangliosidosis B1 variant. J Inherit Metab Dis. 1991;14:715\u201320. https:\/\/doi.org\/10.1007\/BF01799940.","journal-title":"J Inherit Metab Dis"},{"key":"4430_CR21","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1038\/nmeth.2089","volume":"9","author":"CA Schneider","year":"2012","unstructured":"Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nat Methods. 2012;9:671\u20135. https:\/\/doi.org\/10.1038\/nmeth.2089.","journal-title":"Nat Methods"},{"key":"4430_CR22","doi-asserted-by":"publisher","first-page":"103935","DOI":"10.1016\/j.xpro.2025.103935","volume":"6","author":"B Doray","year":"2025","unstructured":"Doray B, Henn D, Yang X, Li M, Dickson P. Protocol to measure endogenous GlcNAc-1-phosphotransferase activity in SK-MEL-30 cells. STAR Protoc. 2025;6:103935. https:\/\/doi.org\/10.1016\/j.xpro.2025.103935.","journal-title":"STAR Protoc"},{"key":"4430_CR23","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1111\/jnc.14564","volume":"148","author":"L Bajaj","year":"2019","unstructured":"Bajaj L, Lotfi P, Pal R, di Ronza A, Sharma J, Sardiello M. Lysosome biogenesis in health and disease. J Neurochem Blackwell Publishing Ltd. 2019;148:573\u201389. https:\/\/doi.org\/10.1111\/jnc.14564.","journal-title":"J Neurochem Blackwell Publishing Ltd"},{"key":"4430_CR24","doi-asserted-by":"publisher","first-page":"2524","DOI":"10.1016\/j.molcel.2023.06.004","volume":"83","author":"J Zhang","year":"2023","unstructured":"Zhang J, Zeng W, Han Y, Lee W-R, Liou J, Jiang Y. Lysosomal LAMP proteins regulate lysosomal pH by direct inhibition of the TMEM175 channel. Mol Cell Cell Press. 2023;83:2524\u2013e25397. https:\/\/doi.org\/10.1016\/j.molcel.2023.06.004.","journal-title":"Mol Cell Cell Press"},{"key":"4430_CR25","doi-asserted-by":"publisher","first-page":"35283","DOI":"10.1074\/jbc.M111.267930","volume":"286","author":"T Otomo","year":"2011","unstructured":"Otomo T, Higaki K, Nanba E, Ozono K, Sakai N. Lysosomal Storage Causes Cellular Dysfunction in Mucolipidosis II Skin Fibroblasts. J Biol Chem. 2011;286:35283\u201390. https:\/\/doi.org\/10.1074\/jbc.M111.267930.","journal-title":"J Biol Chem"},{"key":"4430_CR26","doi-asserted-by":"publisher","first-page":"23936","DOI":"10.1074\/jbc.M110.129684","volume":"285","author":"S Pohl","year":"2010","unstructured":"Pohl S, Tiede S, Marschner K, Encarna\u00e7\u00e3o M, Castrichini M, Kollmann K, et al. Proteolytic Processing of the \u03b3-Subunit Is Associated with the Failure to Form GlcNAc-1-phosphotransferase Complexes and Mannose 6-Phosphate Residues on Lysosomal Enzymes in Human Macrophages. J Biol Chem. 2010;285:23936\u201344. https:\/\/doi.org\/10.1074\/jbc.M110.129684.","journal-title":"J Biol Chem"},{"key":"4430_CR27","doi-asserted-by":"publisher","first-page":"108596","DOI":"10.1016\/j.ymgme.2024.108596","volume":"143","author":"L Badenetti","year":"2024","unstructured":"Badenetti L, Yu S-H, Colonna MB, Hull R, Bethard JR, Ball L, et al. Multi-omic analysis of a mucolipidosis II neuronal cell model uncovers involvement of pathways related to neurodegeneration and drug metabolism. Mol Genet Metab Acad Press Inc. 2024;143:108596. https:\/\/doi.org\/10.1016\/j.ymgme.2024.108596.","journal-title":"Mol Genet Metab Acad Press Inc"},{"key":"4430_CR28","doi-asserted-by":"publisher","unstructured":"Boonen M, van Meel E, Oorschot V, Klumperman J, Kornfeld S. Vacuolization of mucolipidosis type II mouse exocrine gland cells represents accumulation of autolysosomes. Parton RG, editor. Mol Biol Cell. 2011;22:1135\u201347. https:\/\/doi.org\/10.1091\/mbc.e10-07-0584.","DOI":"10.1091\/mbc.e10-07-0584"},{"key":"4430_CR29","doi-asserted-by":"publisher","first-page":"2661","DOI":"10.1093\/brain\/aws209","volume-title":"Lysosomal dysfunction causes neurodegeneration in mucolipidosis II \u2018knock-in\u2019 mice","author":"K Kollmann","year":"2012","unstructured":"Kollmann K, Damme M, Markmann S, Morelle W, Schweizer M, Hermans-Borgmeyer I, et al. Lysosomal dysfunction causes neurodegeneration in mucolipidosis II \u2018knock-in\u2019 mice. Volume 135. Brain: Oxford University Press; 2012. pp. 2661\u201375. https:\/\/doi.org\/10.1093\/brain\/aws209."},{"key":"4430_CR30","doi-asserted-by":"publisher","first-page":"1775","DOI":"10.3390\/biom11121775","volume":"11","author":"C Fern\u00e1ndez-Pereira","year":"2021","unstructured":"Fern\u00e1ndez-Pereira C, San Mill\u00e1n-Tejado B, Gallardo-G\u00f3mez M, P\u00e9rez-M\u00e1rquez T, Alves-Villar M, Melc\u00f3n-Crespo C, et al. Therapeutic Approaches in Lysosomal Storage Diseases. Biomolecules MDPI. 2021;11:1775. https:\/\/doi.org\/10.3390\/biom11121775.","journal-title":"Biomolecules MDPI"},{"key":"4430_CR31","doi-asserted-by":"publisher","unstructured":"Qian Y, van Meel E, Flanagan-Steet H, Yox A, Steet R, Kornfeld S. Analysis of Mucolipidosis II\/III GNPTAB Missense Mutations Identifies Domains of UDP-GlcNAc:lysosomal Enzyme GlcNAc-1-phosphotransferase Involved in Catalytic Function and Lysosomal Enzyme Recognition. J Biol Chem. American Society for Biochemistry and Molecular Biology Inc.; 2015 Jan. https:\/\/doi.org\/10.1074\/jbc.M114.612507.","DOI":"10.1074\/jbc.M114.612507"},{"key":"4430_CR32","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.biocel.2017.09.006","volume":"92","author":"NF Ludwig","year":"2017","unstructured":"Ludwig NF, Velho RV, Sperb-Ludwig F, Acosta AX, Ribeiro EM, Kim CA, et al. GNPTAB missense mutations cause loss of GlcNAc-1-phosphotransferase activity in mucolipidosis type II through distinct mechanisms. Int J Biochem Cell Biol Elsevier. 2017;92:90\u20134. https:\/\/doi.org\/10.1016\/j.biocel.2017.09.006.","journal-title":"Int J Biochem Cell Biol Elsevier"},{"key":"4430_CR33","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1002\/humu.23928","volume":"41","author":"T Danyukova","year":"2020","unstructured":"Danyukova T, Ludwig NF, Velho RV, Harms FL, G\u00fcne\u015f N, Tidow H, et al. Combined in vitro and in silico analyses of missense mutations in GNPTAB provide new insights into the molecular bases of mucolipidosis II and III alpha\/beta. Hum Mutat John Wiley Sons Inc. 2020;41:133\u20139. https:\/\/doi.org\/10.1002\/humu.23928.","journal-title":"Hum Mutat John Wiley Sons Inc"},{"key":"4430_CR34","doi-asserted-by":"publisher","first-page":"101702","DOI":"10.1016\/j.jbc.2022.101702","volume":"298","author":"S Du","year":"2022","unstructured":"Du S, Wang G, Zhang Z, Ma C, Gao N, Xiao J. Structural insights into how GlcNAc-1-phosphotransferase directs lysosomal protein transport. J Biol Chem Am Soc Biochem Mol Biology Inc. 2022;298:101702. https:\/\/doi.org\/10.1016\/j.jbc.2022.101702.","journal-title":"J Biol Chem Am Soc Biochem Mol Biology Inc"},{"key":"4430_CR35","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1038\/s41594-022-00748-0","volume":"29","author":"H Li","year":"2022","unstructured":"Li H, Lee W-S, Feng X, Bai L, Jennings BC, Liu L, et al. Structure of the human GlcNAc-1-phosphotransferase \u03b1\u03b2 subunits reveals regulatory mechanism for lysosomal enzyme glycan phosphorylation. Nat Struct Mol Biol Nat Res. 2022;29:348\u201356. https:\/\/doi.org\/10.1038\/s41594-022-00748-0.","journal-title":"Nat Struct Mol Biol Nat Res"}],"container-title":["Orphanet Journal of Rare Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13023-026-04430-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-026-04430-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-026-04430-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:10:24Z","timestamp":1788135024000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s13023-026-04430-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,17]]},"references-count":35,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["4430"],"URL":"https:\/\/doi.org\/10.1186\/s13023-026-04430-2","relation":{},"ISSN":["1750-1172"],"issn-type":[{"value":"1750-1172","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,17]]},"assertion":[{"value":"11 March 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 June 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of The National Institute of Health Doutor Ricardo Jorge, and by the \u201cCell Line and DNA Biobank from Patients Affected by Genetic Diseases\u201d of Istituto Giannina Gaslini.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no conflicts of interest.","order":3,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"309"}}