{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T15:32:06Z","timestamp":1786375926309,"version":"build-2736575974"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"17","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Jaeken-Theunissen CDG Fund"},{"name":"FWO-FNRS WEAVE program","award":["G061524N"],"award-info":[{"award-number":["G061524N"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mucolipidosis type II is an autosomal recessive lysosomal storage disease resulting from biallelic variants in the GNPTAB gene encoding the N-acetylglucosamine phosphotransferase \u03b1\/\u03b2 subunits. Deficiency of this enzyme disrupts the mannose-6-phosphate (M6P) trafficking pathway, resulting in mistargeting of lysosomal acid hydrolases. Subsequently, lysosomal accumulation of undegraded macromolecules gives rise to a clinical phenotype with developmental\/intellectual disability, skeletal deformities, coarse features, and cardiopulmonary dysfunction. Here, we report a cohort of eight patients (7 Egyptians and 1 Yemeni) from seven families with three reported homozygous pathogenic variants and three unreported variants (p.(Asn750Ilefs*4), p.(Val795Glyfs*7), and c.3602\u2009+\u20092\u00a0T\u2009&amp;gt;\u2009C). In addition, the GNPTAB gene was ablated in the H. sapiens haploid HAP1 cells by CRISPR-Cas9 editing, to investigate the potential of this cell line for the assessment of variant pathogenicity. This included introduction of the recurrent c.3503_3504delTC variant. A phenotype of impaired autophagic flux was recapitulated, suggesting that HAP1 cells are a suitable model for this disorder.<\/jats:p>","DOI":"10.1093\/hmg\/ddag068","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T11:41:56Z","timestamp":1784202116000},"source":"Crossref","is-referenced-by-count":0,"title":["Mucolipidosis II: novel variants, clinical variation and assessment of HAP1 cells as a disease model"],"prefix":"10.1093","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7545-2015","authenticated-orcid":false,"given":"Noura R","family":"Eissa","sequence":"first","affiliation":[{"name":"Medical Molecular genetics Department, Human Genetics and Genome Research Institute, National Research Centre , 33 El Buhouth St\u060c Ad Doqi, Dokki, Cairo Governorate, 12622 ,","place":["Egypt"]},{"name":"Academy of Scientific Research & Technology (ASRT) , 101 Kasr Al-Ainy St, Cairo Governorate, 11516 ,","place":["Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghada M","family":"Abdel-Salam","sequence":"additional","affiliation":[{"name":"Clinical genetics Department, Human Genetics and Genome Research Institute, National Research Centre , 33 El Buhouth St\u060c Ad Doqi, Dokki, Cairo Governorate, 12622 ,","place":["Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelina","family":"Kretkiewicz","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Diagnosis, Center for Human Genetics, KU Leuven ,","place":["UZ Leuven Gasthuisberg Campus, Herestraat 49, 3000 Leuven, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eline","family":"Pieters","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Diagnosis, Center for Human Genetics, KU Leuven ,","place":["UZ Leuven Gasthuisberg Campus, Herestraat 49, 3000 Leuven, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaak","family":"Jaeken","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Center for Metabolic Diseases, University Hospitals Leuven ,","place":["Herestraat 49, 3000 Leuven, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gert","family":"Matthijs","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Diagnosis, Center for Human Genetics, KU Leuven ,","place":["UZ Leuven Gasthuisberg Campus, Herestraat 49, 3000 Leuven, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2252-8730","authenticated-orcid":false,"given":"Matthew P","family":"Wilson","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Diagnosis, Center for Human Genetics, KU Leuven ,","place":["UZ Leuven Gasthuisberg Campus, Herestraat 49, 3000 Leuven, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"2026081011261655700_ref1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21186812","article-title":"Mucolipidoses overview: past, present, and future","volume":"21","author":"Khan","year":"2020","journal-title":"Int J Mol Sci"},{"key":"2026081011261655700_ref2","doi-asserted-by":"publisher","first-page":"2047","DOI":"10.1038\/s41436-021-01244-4","article-title":"Mucolipidosis type II and type III: a systematic review of 843 published cases","volume":"23","author":"Dogterom","year":"2021","journal-title":"Genet Med"},{"key":"2026081011261655700_ref3","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1038\/s41594-022-00748-0","article-title":"Structure of the human GlcNAc-1-phosphotransferase alphabeta subunits reveals regulatory mechanism for lysosomal enzyme glycan 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