{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T01:11:14Z","timestamp":1783991474145,"version":"3.55.0"},"posted":{"date-parts":[[2025,5,7]]},"group-title":"Genetic and Genomic Medicine","reference-count":106,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T00:00:00Z","timestamp":1746576000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,5,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Sex-specific penetrance in autosomal dominant Mendelian conditions is largely understudied. The neurodevelopmental disorder Pilarowski-Bjornsson syndrome (PILBOS) was initially described in females. Here, we describe the clinical and genetic characteristics of the largest PILBOS cohort to date, showing that both sexes can exhibit PILBOS features, although males are overrepresented. A mouse model carrying a human-derived\n                  <jats:italic>Chd1<\/jats:italic>\n                  missense variant (\n                  <jats:italic>\n                    Chd1\n                    <jats:sup>R<\/jats:sup>\n                  <\/jats:italic>\n                  <jats:sup>616<\/jats:sup>\n                  <jats:italic>\n                    <jats:sup>Q<\/jats:sup>\n                  <\/jats:italic>\n                  <jats:sup>\/+<\/jats:sup>\n                  ) displays female-restricted phenotypes, including growth deficiency, anxiety and hypotonia. Orchiectomy unmasks a growth deficiency phenotype in male\n                  <jats:italic>\n                    Chd1\n                    <jats:sup>R<\/jats:sup>\n                  <\/jats:italic>\n                  <jats:sup>616<\/jats:sup>\n                  <jats:italic>\n                    <jats:sup>Q<\/jats:sup>\n                  <\/jats:italic>\n                  <jats:sup>\/+<\/jats:sup>\n                  mice, while testosterone rescues the phenotype in females, implicating androgens in phenotype modulation. In the gnomAD and UK Biobank databases, rare missense variants in\n                  <jats:italic>CHD1<\/jats:italic>\n                  are overrepresented in males, supporting a male protective effect. We identify 33 additional highly constrained autosomal genes with missense variant overrepresentation in males. Our results support androgen-regulated sexual dimorphism in PILBOS and open novel avenues to understand the mechanistic basis of sexual dimorphism in other autosomal Mendelian disorders.\n                <\/jats:p>\n                <jats:sec id=\"s1\">\n                  <jats:title>Graphical Abstract<\/jats:title>\n                  <jats:fig id=\"ufig1\" position=\"float\" orientation=\"portrait\" fig-type=\"figure\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"25326635v1_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>","DOI":"10.1101\/2025.05.06.25326635","type":"posted-content","created":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T22:00:33Z","timestamp":1746655233000},"source":"Crossref","is-referenced-by-count":1,"title":["Androgens mediate sexual dimorphism in Pilarowski-Bjornsson Syndrome"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0629-6343","authenticated-orcid":false,"given":"Kimberley Jade","family":"Anderson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eirny Tholl","family":"Thorolfsdottir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilana M.","family":"Nodelman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara 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