{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T20:54:28Z","timestamp":1767992068049,"version":"3.49.0"},"reference-count":19,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,11,25]],"date-time":"2022-11-25T00:00:00Z","timestamp":1669334400000},"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":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Deletion of 17p13.3 has varying degrees of severity on brain development based on precise location and size of the deletion. The most severe phenotype is Miller\u2013Dieker syndrome (MDS) which is characterized by lissencephaly, dysmorphic facial features, growth failure, developmental disability, and often early death. Haploinsufficiency of <jats:italic>PAFAH1B1<\/jats:italic> is responsible for the characteristic lissencephaly in MDS. The precise role of <jats:italic>YWHAE<\/jats:italic> haploinsufficiency in MDS is unclear. Case reports are beginning to elucidate the phenotypes of individuals with 17p13.3 deletions that have deletion of <jats:italic>YWHAE<\/jats:italic> but do not include deletion of <jats:italic>PAFAH1B1<\/jats:italic>. Through our clinical genetics practice, we identified four individuals with 17p13.3 deletion that include <jats:italic>YWHAE<\/jats:italic> but not <jats:italic>PAFAH1B1.<\/jats:italic> These patients have a similar phenotype of dysmorphic facial features, developmental delay, and leukoencephalopathy. In a review of the literature, we identified 19 patients with 17p13.3 microdeletion sparing <jats:italic>PAFAH1B1<\/jats:italic> but deleting <jats:italic>YWHAE<\/jats:italic>. Haploinsufficiency of <jats:italic>YWHAE<\/jats:italic> is associated with brain abnormalities including cystic changes. These individuals have high frequency of epilepsy, intellectual disability, and dysmorphic facial features including prominent forehead, epicanthal folds, and broad nasal root. We conclude that deletion of 17p13.3 excluding <jats:italic>PAFAH1B1<\/jats:italic> but including <jats:italic>YWHAE<\/jats:italic> is associated with a consistent phenotype and should be considered a distinct condition from MDS.<\/jats:p>","DOI":"10.1002\/ajmg.a.63057","type":"journal-article","created":{"date-parts":[[2022,11,26]],"date-time":"2022-11-26T14:26:22Z","timestamp":1669472782000},"page":"526-539","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Further expansion and confirmation of phenotype in rare loss of <scp><i>YWHAE<\/i><\/scp> gene distinct from <scp>Miller\u2013Dieker<\/scp> syndrome"],"prefix":"10.1002","volume":"191","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4709-5700","authenticated-orcid":false,"given":"Elizabeth K.","family":"Baker","sequence":"first","affiliation":[{"name":"Division of Human Genetics Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"},{"name":"Department of Pediatrics University of Cincinnati College of Medicine  Cincinnati Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Casey J.","family":"Brewer","sequence":"additional","affiliation":[{"name":"Division of Human Genetics Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2468-2689","authenticated-orcid":false,"given":"Leonardo","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Division of Human Genetics Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"},{"name":"Department of Pediatrics University of Cincinnati College of Medicine  Cincinnati Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Schapiro","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Cincinnati College of Medicine  Cincinnati Ohio USA"},{"name":"Division of Neurology Cincinnati Children's Hospital Medicine  Cincinnati Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey","family":"Tenney","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Cincinnati College of Medicine  Cincinnati Ohio USA"},{"name":"Division of Neurology Cincinnati Children's Hospital Medicine  Cincinnati Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heather M.","family":"Wied","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Cincinnati College of Medicine  Cincinnati Ohio USA"},{"name":"Division of Neurology Cincinnati Children's Hospital Medicine  Cincinnati Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beth M.","family":"Kline\u2010Fath","sequence":"additional","affiliation":[{"name":"Division of Radiology University of Cincinnati College of Medicine  Cincinnati Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresa A.","family":"Smolarek","sequence":"additional","affiliation":[{"name":"Division of Human Genetics Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"},{"name":"Department of Pediatrics University of Cincinnati College of Medicine  Cincinnati Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3991-135X","authenticated-orcid":false,"given":"K. Nicole","family":"Weaver","sequence":"additional","affiliation":[{"name":"Division of Human Genetics Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"},{"name":"Department of Pediatrics University of Cincinnati College of Medicine  Cincinnati Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0770-5516","authenticated-orcid":false,"given":"Robert J.","family":"Hopkin","sequence":"additional","affiliation":[{"name":"Division of Human Genetics Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"},{"name":"Department of Pediatrics University of Cincinnati College of Medicine  Cincinnati Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,11,25]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1159\/000452753"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2018.00080"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2009.069906"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1086\/374320"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tjog.2017.12.022"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddw270"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38245"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-018-0358-0"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31402"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.03.047"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2009.069112"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2009.067637"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13056"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm241"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-020-04424-3"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2010.06.009"},{"issue":"5","key":"e_1_2_8_18_1","first-page":"597","article-title":"Detection of submicroscopic deletions in band 17p13 in patients with the Miller\u2013Dieker syndrome","volume":"43","author":"Schwartz C. 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