{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T21:11:45Z","timestamp":1768511505539,"version":"3.49.0"},"posted":{"date-parts":[[2024,4,22]]},"group-title":"Genomics","reference-count":20,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,4,22]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n                <jats:p>\n                  P21-activated kinase 2 (PAK2) is a serine\/threonine kinase essential for a variety of cellular processes including signal transduction, cellular survival, proliferation, and migration. A recent report proposed monoallelic\n                  <jats:italic>PAK2<\/jats:italic>\n                  variants cause Knobloch syndrome type 2 (KNO2)\u2014a developmental disorder primarily characterized by ocular anomalies. Here, we identified a novel\n                  <jats:italic>de novo<\/jats:italic>\n                  heterozygous missense variant in\n                  <jats:italic>PAK2<\/jats:italic>\n                  , NM_002577.4:c.1273G&gt;A, p.(D425N), by whole genome sequencing in an individual with features consistent with KNO2. Notable clinical phenotypes include global developmental delay, congenital retinal detachment, mild cerebral ventriculomegaly, hypotonia, FTT, pyloric stenosis, feeding intolerance, patent ductus arteriosus, and mild facial dysmorphism. The p.(D425N) variant lies within the protein kinase domain and is predicted to be functionally damaging by\n                  <jats:italic>in silico<\/jats:italic>\n                  analysis. Previous clinical genetic testing did not report this variant due to unknown relevance of\n                  <jats:italic>PAK2<\/jats:italic>\n                  variants at the time of testing, highlighting the importance of reanalysis. Our findings also substantiate the candidacy of\n                  <jats:italic>PAK2<\/jats:italic>\n                  variants in KNO2 and expand the KNO2 clinical spectrum.\n                <\/jats:p>","DOI":"10.1101\/2024.04.18.590108","type":"posted-content","created":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T17:35:12Z","timestamp":1713807312000},"source":"Crossref","is-referenced-by-count":2,"title":["A\n                  <i>de novo<\/i>\n                  variant in\n                  <i>PAK2<\/i>\n                  detected in an individual with Knobloch type 2 syndrome"],"prefix":"10.64898","author":[{"given":"Elizabeth A.","family":"Werren","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louisa","family":"Kalsner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Ewald","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Peracchio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cameron","family":"King","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Purva","family":"Vats","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter A.","family":"Audano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0736-9199","authenticated-orcid":false,"given":"Peter N.","family":"Robinson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark D.","family":"Adams","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5174-6036","authenticated-orcid":false,"given":"Melissa A.","family":"Kelly","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam P.","family":"Matson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024042500200794000_2024.04.18.590108v1.1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddab026"},{"key":"2024042500200794000_2024.04.18.590108v1.2","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5318.1571"},{"key":"2024042500200794000_2024.04.18.590108v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2008.06.002"},{"key":"2024042500200794000_2024.04.18.590108v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.09.016"},{"issue":"3","key":"2024042500200794000_2024.04.18.590108v1.5","first-page":"1663","article-title":"A familial 3q28q29 duplication induced mild intellectual disability: case presentation and literature review","volume":"14","year":"2022","journal-title":"Am J Transl 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