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A wide range of variants has been reported for different countries and ethnic groups. We collected, analyzed and uniformly summarized all published\n                      <jats:italic>IDS<\/jats:italic>\n                      gene variants reported in literature up to June 2023, here providing the first worldwide review and classification.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Data was obtained from a literature search, conducted in PubMed and Google. All data was analyzed to define the most common alleles, geographic distribution and genotype-phenotype correlation. Moreover, point variants were classified according to their pathogenicity, based on the ACMG guidelines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Several types of variants have been described in the\n                      <jats:italic>IDS<\/jats:italic>\n                      gene, including intrachromosomal homologous recombination occurring between the homologous regions of\n                      <jats:italic>IDS<\/jats:italic>\n                      gene and its pseudogene\n                      <jats:italic>IDSP1.<\/jats:italic>\n                      Overall, we collected 2852 individuals from 2798 families, including 24 female patients. Most families carried missense variants, followed by large deletions-insertions and complex rearrangements, small frameshift deletions\/insertions and nonsense variants. Based on ACMG guidelines, 62.9% of the 779 point variants were classified as \u201cpathogenic\u201d, 35.4% as \u201clikely pathogenic\u201d, and the remaining 13 variants as having \u201cuncertain significance\u201d.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Data from this study confirmed that MPS II is a genetically very heterogeneous disorder, making genotype-phenotype correlation very challenging and in most cases merely unfeasible. Mutation updates are essential for the correct molecular diagnosis, genetic counseling, prenatal and preimplantation diagnosis, and disease management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40246-024-00701-w","type":"journal-article","created":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T20:20:26Z","timestamp":1733084426000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Molecular basis of mucopolysaccharidosis type II (Hunter syndrome): first review and classification of published IDS gene variants"],"prefix":"10.1186","volume":"18","author":[{"given":"Alessandra","family":"Zanetti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"D\u2019Avanzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosella","family":"Tomanin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,12,2]]},"reference":[{"key":"701_CR1","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1016\/S0959-437X(97)80153-0","volume":"7","author":"G Parenti","year":"1997","unstructured":"Parenti G, Meroni G, Ballabio A. 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