{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T16:39:15Z","timestamp":1776011955962,"version":"3.50.1"},"reference-count":20,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T00:00:00Z","timestamp":1670976000000},"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":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We report a boy with typical clinical features of SHORT syndrome alongside a significant microcephaly and severe developmental delay associated with a de novo single nucleotide missense DNA variant resulting in a single amino acid change in codon 486 of the <jats:italic>PIK3R1<\/jats:italic> gene (<jats:italic>PIK3R1<\/jats:italic> c.1456G&gt;A (p.Ala486Thr)). Our report strikingly coincides with another recently published case from Brazil, describing a 23\u2010year\u2010old woman with the same de novo <jats:italic>PIK3R1<\/jats:italic> DNA variant, who also exhibits SHORT syndrome with severe secondary microcephaly and intellectual disability. On review of the literature, we have identified further cases of <jats:italic>PIK3R1<\/jats:italic>\u2010related SHORT Syndrome with a similar phenotype. We note all these cases (including ours) have variants located in the \u2010inter SH2 domain (iSH2); we speculate that pathogenic iSH2 located <jats:italic>PIK3R1<\/jats:italic> variants are associated with a different and otherwise unreported clinical picture of SHORT syndrome that presents with microcephaly and\/or significant developmental delay\/intellectual disability. The pathogenic mechanism of why these variants apparently lead to a different clinical picture of SHORT syndrome remains unknown.<\/jats:p>","DOI":"10.1002\/ajmg.a.63078","type":"journal-article","created":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T12:12:39Z","timestamp":1671019959000},"page":"850-854","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["<scp>SHORT<\/scp> syndrome with microcephaly and developmental delay"],"prefix":"10.1002","volume":"191","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4041-0971","authenticated-orcid":false,"given":"Viraj","family":"Patel","sequence":"first","affiliation":[{"name":"North West Thames Regional Genetics Service  NHS, Northwick Park &amp; St Mark's Hospitals London Harrow UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Cui","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Department of Metabolism, Digestions and Reproduction Imperial College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan M.","family":"Cobben","sequence":"additional","affiliation":[{"name":"North West Thames Regional Genetics Service  NHS, Northwick Park &amp; St Mark's Hospitals London Harrow UK"},{"name":"Faculty of Medicine, Department of Metabolism, Digestions and Reproduction Imperial College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,12,14]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12688"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2350-15-51"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2017.03.004"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03867-9"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.05.023"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2019.11.013"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.06.005"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62660"},{"issue":"2","key":"e_1_2_6_10_1","first-page":"39","article-title":"Malformation syndromes. A selected miscellany","volume":"11","author":"Gorlin R. J.","year":"1975","journal-title":"Birth Defects Original Article Series"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2009.10.016"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13052-017-0362-z"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25998"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12881-020-01146-3"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1009652107"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.05.019"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2882"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdi.13549"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.137075"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.1385"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.63078","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.63078","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.63078","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,18]],"date-time":"2023-08-18T01:35:52Z","timestamp":1692322552000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.63078"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,14]]},"references-count":20,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2023,3]]}},"alternative-id":["10.1002\/ajmg.a.63078"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.63078","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,14]]},"assertion":[{"value":"2022-07-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}