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Many ciliopathy genes show a spectrum of severity, producing a clinical continuum from lethal MKS to the less severe Joubert syndrome (JS). Using genome and exome sequencing analysis, we identified four unrelated children with JS who harbor rare biallelic variants in\n                    <jats:italic>TXNDC15.<\/jats:italic>\n                    In contrast to the biallelic truncating variants typical of MKS, all individuals with JS carried a missense variant\n                    <jats:italic>in trans<\/jats:italic>\n                    with a truncating variant. Three of four missense variants cluster within the functionally critical thioredoxin domain. In silico structural modeling using AlphaFold and variant effect prediction (AlphaMissense, DynaMut2) support a deleterious effect on protein stability and function for the majority of these missense variants. This work expands the phenotypic spectrum of\n                    <jats:italic>TXNDC15<\/jats:italic>\n                    \u2010related ciliopathies to include JS. All four individuals carried a missense allele\n                    <jats:italic>in trans<\/jats:italic>\n                    with a truncating allele. Our findings underscore the importance of including\n                    <jats:italic>TXNDC15<\/jats:italic>\n                    in the genetic diagnosis of JS.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.70317","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T03:16:01Z","timestamp":1791256561000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Expanding the Phenotypic Spectrum of\n                    <scp>\n                      <i>TXNDC15<\/i>\n                    <\/scp>\n                    \u2010Related Ciliopathies to Include Joubert Syndrome"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6005-7111","authenticated-orcid":false,"given":"Zachary T.","family":"Sentell","sequence":"first","affiliation":[{"name":"Department of Human Genetics McGill University  Montreal Canada"},{"name":"Faculty of Medical Sciences, Biosciences Institute Newcastle University  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9128-5173","authenticated-orcid":false,"given":"Robert","family":"Geraghty","sequence":"additional","affiliation":[{"name":"Faculty of Medical Sciences, Biosciences Institute Newcastle University  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana E.","family":"Arcila\u2010Galvis","sequence":"additional","affiliation":[{"name":"Faculty of Medical Sciences, Biosciences Institute Newcastle University  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7733-8507","authenticated-orcid":false,"given":"Praveen","family":"Dhondurao\u2010Sudhindar","sequence":"additional","affiliation":[{"name":"Faculty of Medical Sciences, Biosciences Institute Newcastle University  Newcastle upon Tyne 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