{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:51:13Z","timestamp":1779151873238,"version":"3.51.4"},"reference-count":30,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T00:00:00Z","timestamp":1738022400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    P21\u2010activated 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 genome sequencing in an individual with features consistent with KNO2. Notable clinical phenotypes observed in this individual were global developmental delay, congenital retinal detachment, mild cerebral ventriculomegaly, hypotonia, failure to thrive, 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 in silico 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 substantiate the candidacy of\n                    <jats:italic>PAK2<\/jats:italic>\n                    variants in KNO2 and expand the KNO2 clinical phenotypic spectrum.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.64006","type":"journal-article","created":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T01:13:38Z","timestamp":1738113218000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Phenotypic Expansion of Knobloch Syndrome Type 2 in an Individual With a De Novo\n                    <scp>\n                      <i>PAK2<\/i>\n                    <\/scp>\n                    Variant"],"prefix":"10.1002","volume":"197","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0151-2564","authenticated-orcid":false,"given":"Elizabeth A.","family":"Werren","sequence":"first","affiliation":[{"name":"The Jackson Laboratory for Genomic Medicine  Farmington Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0484-2013","authenticated-orcid":false,"given":"Louisa","family":"Kalsner","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Connecticut School of Medicine  Farmington Connecticut USA"},{"name":"Division of Genetics Connecticut Children's Medical Center  Hartford Connecticut USA"},{"name":"Division of Neurology Connecticut Children's Medical Center  Hartford Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica M.","family":"Ewald","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory for Genomic Medicine  Farmington Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Peracchio","sequence":"additional","affiliation":[{"name":"Division of Genetics Connecticut Children's Medical Center  Hartford Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cameron","family":"King","sequence":"additional","affiliation":[{"name":"Department of Research Connecticut Children's Medical Center  Hartford Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Purva","family":"Vats","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory for Genomic Medicine  Farmington Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter A.","family":"Audano","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory for Genomic Medicine  Farmington Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0736-9199","authenticated-orcid":false,"given":"Peter N.","family":"Robinson","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory for Genomic Medicine  Farmington Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark D.","family":"Adams","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory for Genomic Medicine  Farmington Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa A.","family":"Kelly","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory for Genomic Medicine  Farmington Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam P.","family":"Matson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Connecticut School of Medicine  Farmington Connecticut USA"},{"name":"Division of Neonatology Connecticut Children's Medical Center  Hartford Connecticut USA"},{"name":"Department of Immunology, UConn Health  Farmington Connecticut 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Familial 3q28q29 Duplication Induced Mild Intellectual Disability: Case Presentation and Literature Review","volume":"14","author":"Wen X.","year":"2022","journal-title":"American Journal of Translational Research"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1101\/2024.04.18.590108"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/(sici)1096\u20108628(19980707)78:3<286::aid\u2010ajmg16>3.0.co;2\u2010b"}],"container-title":["American Journal of Medical Genetics Part 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