{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T09:30:57Z","timestamp":1775122257353,"version":"3.50.1"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T00:00:00Z","timestamp":1775088000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is an X-linked lysosomal storage disorder caused by variants in the\n                      <jats:italic>IDS<\/jats:italic>\n                      gene. This study reports a male infant with a novel hemizygous frameshift mutation (\n                      <jats:italic>IDS<\/jats:italic>\n                      gene: NM_000202.8, c.1133delA, p.Phe378SerfsTer13). We will investigate the functional consequences and pathogenic mechanisms of this novel mutation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The mutation c.1133delA in the\n                      <jats:italic>IDS<\/jats:italic>\n                      gene of this patient was confirmed by Sanger sequencing. Structural modeling was performed to assess the impact of the mutation on protein architecture. Additionally, a genome-scale metabolic model was employed to simulate the metabolic consequences of IDS deficiency.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Structural analysis revealed deletion of the sulfatase domain 2 (SD2) and disruption of the ligand-binding pocket. Metabolic modeling demonstrated that perturbations were highly localized, affecting only a limited subset of reactions primarily confined to glycosaminoglycan degradation pathways, without detectable impact on core cellular metabolism. The model further predicted accumulation of glycosaminoglycan-related intermediates, consistent with known biochemical hallmarks and clinical manifestations of MPS II.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This study demonstrates the pathogenicity of the mutation c.1133delA, our findings highlight the value of metabolic network analysis in understanding disease mechanisms and identifying potential therapeutic targets for MPS II.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmolb.2026.1734111","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T08:32:41Z","timestamp":1775118761000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Revealing the role of a novel IDS gene mutation in mucpolysaccharidosis type II: insights from computational analysis"],"prefix":"10.3389","volume":"13","author":[{"given":"Shanzhou","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Neonatology, Yuexi Hospital of The Sixth Affiliated Hospital, Sun Yat-sen University\/Xinyi People\u2019s Hospital","place":["Xinyi Maoming, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chonghan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Yuexi Hospital of The Sixth Affiliated Hospital, Sun Yat-sen University\/Xinyi People\u2019s Hospital","place":["Xinyi Maoming, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuyuan","family":"Zhi","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Yuexi Hospital of The Sixth Affiliated Hospital, Sun Yat-sen University\/Xinyi People\u2019s Hospital","place":["Xinyi Maoming, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zengling","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Yuexi Hospital of The Sixth Affiliated Hospital, Sun Yat-sen University\/Xinyi People\u2019s Hospital","place":["Xinyi Maoming, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fei","family":"Ma","sequence":"additional","affiliation":[{"name":"Maternal & Child Health Research Institute, Zhuhai Center for Maternal and Child Health Care","place":["Zhuhai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Congcong","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The Sixth Affiliated Hospital, Sun Yat-sen University","place":["Guangzhou, Guangdong, China"]},{"name":"Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University","place":["Guangzhou, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sitao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Yuexi Hospital of The Sixth Affiliated Hospital, Sun Yat-sen University\/Xinyi People\u2019s Hospital","place":["Xinyi Maoming, Guangdong, China"]},{"name":"Department of Pediatrics, The Sixth Affiliated Hospital, Sun Yat-sen University","place":["Guangzhou, Guangdong, China"]},{"name":"Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University","place":["Guangzhou, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"W530","DOI":"10.1093\/nar\/gkab294","article-title":"PLIP 2021: expanding the scope of the protein\u2013ligand interaction profiler to DNA and RNA","volume":"49","author":"Adasme","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1038\/nbt.4072","article-title":"Recon3D enables a three-dimensional view of gene variation in human metabolism","volume":"36","author":"Brunk","year":"2018","journal-title":"Nat. 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