{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T21:57:30Z","timestamp":1768773450345,"version":"3.49.0"},"reference-count":31,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,12,6]],"date-time":"2024-12-06T00:00:00Z","timestamp":1733443200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021856","name":"Ministero dell'Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100021856","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Alteration in the ubiquitin\u2010proteasome system results in human disorders with neurological and\/or autoinflammatory presentation. Haploinsufficiency of\n                    <jats:italic>PSMD12<\/jats:italic>\n                    , which encodes a subunit of the core component of the proteasome, causes Stankiewicz\u2010Isidor syndrome (STISS), characterized by intellectual disability, autism spectrum disorder, craniofacial dysmorphisms, with or without other congenital anomalies, and autoinflammation. We described six patients (four adults) from two unrelated families carrying a known p.(Arg289*) or a novel p.(Tyr111*)\n                    <jats:italic>PSMD12<\/jats:italic>\n                    variant. Portraying a completely penetrant condition with inter\u2010 and intra\u2010familiar clinical variability, all individuals presented with developmental delay, intellectual disability, craniofacial, and skeletal anomalies. Novel findings in our cohort included unilateral ectopic fingernail, cholesteatoma, oligodontia, and the occurrence of an ovarian teratoma. Most subjects had acne, short stature, and developed obesity since late childhood. Eating behavior was reported. Good sociality and behavioral concern emerged as well. None presented clinical manifestations of autoinflammation and the detected IFN\u2010I signature perturbations were not specific. Together with a complete literature review, we expanded the clinical spectrum of STISS, highlighting the relevance of inherited variants, and discussing challenges in diagnosis and management. We finally consider the intriguing role of\n                    <jats:italic>PSMD12<\/jats:italic>\n                    in human development and propose to index \u201conychoheterotopia\u201d among the Human Phenotype Ontology terms.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.63953","type":"journal-article","created":{"date-parts":[[2024,12,6]],"date-time":"2024-12-06T07:54:08Z","timestamp":1733471648000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Does It Run in Your Family? Inherited Truncating\n                    <scp>\n                      <i>PSMD12<\/i>\n                    <\/scp>\n                    Variants Broaden the Phenotypic Spectrum of Stankiewicz\u2010Isidor Syndrome"],"prefix":"10.1002","volume":"197","author":[{"given":"Agnese","family":"Feresin","sequence":"first","affiliation":[{"name":"Department of Medicine, Surgery and Health Sciences University of Trieste  Trieste Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7432-4708","authenticated-orcid":false,"given":"Beatrice","family":"Spedicati","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Health Sciences University of Trieste  Trieste Italy"},{"name":"Institute for Maternal and Child Health, IRCCS \u201cBurlo\u00a0Garofolo\u201d  Trieste Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefania","family":"Zampieri","sequence":"additional","affiliation":[{"name":"Institute for Maternal and Child Health, IRCCS \u201cBurlo\u00a0Garofolo\u201d  Trieste Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Morgan","sequence":"additional","affiliation":[{"name":"Institute for Maternal and Child Health, IRCCS \u201cBurlo\u00a0Garofolo\u201d  Trieste Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Magnolato","sequence":"additional","affiliation":[{"name":"Institute for Maternal and Child Health, IRCCS \u201cBurlo\u00a0Garofolo\u201d  Trieste Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Tesser","sequence":"additional","affiliation":[{"name":"Institute for Maternal and Child Health, IRCCS \u201cBurlo\u00a0Garofolo\u201d  Trieste Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alberto","family":"Tommasini","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Health Sciences University of Trieste  Trieste Italy"},{"name":"Institute for Maternal and Child Health, IRCCS \u201cBurlo\u00a0Garofolo\u201d  Trieste Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Teresa","family":"Bonati","sequence":"additional","affiliation":[{"name":"Institute for Maternal and Child Health, IRCCS \u201cBurlo\u00a0Garofolo\u201d  Trieste Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giorgia","family":"Girotto","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Health Sciences University of Trieste  Trieste Italy"},{"name":"Institute for Maternal and Child Health, IRCCS \u201cBurlo\u00a0Garofolo\u201d  Trieste Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flavio","family":"Faletra","sequence":"additional","affiliation":[{"name":"Institute for Maternal and Child Health, IRCCS \u201cBurlo\u00a0Garofolo\u201d  Trieste Italy"},{"name":"Institute of Medical Genetics, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC)  Udine Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,12,6]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.200390"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010022\u201002213\u2010z"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13102"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2024.104932"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature21062"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2020.03.095"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2021.733012"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.4081\/dr.2021.9068"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13071513"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/1096\u20108628(20010201)98:4<330::aid\u2010ajmg1104>3.0.co;2\u2010d"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2019.00485"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38711"},{"key":"e_1_2_11_14_1","unstructured":"Human Phenotype Ontology. n.d.Accessed\u00a0July 29 \u00a02024.https:\/\/hpo.jax.org\/."},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gim.2021.09.005"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.32688"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2017.01.003"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13048\u2010018\u20100448\u20102"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aar6731"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436\u2010019\u20100693\u20109"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0363\u20105023(78)80035\u20105"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/7803136"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2018.04.014"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2009.11.018"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"issue":"3","key":"e_1_2_11_26_1","first-page":"235","article-title":"Onychoheterotopia With Polyonychia Associated With Pierre Robin Syndrome: Apropos of a New Case. (Trial of Classifying Nail Ectopia)","volume":"113","author":"Roger H.","year":"1986","journal-title":"Annales De Dermatologie et De Venereologie"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aab3897"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1517\/14728222.2013.815728"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2023.03.017"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gim.2022.02.014"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.cn511374\u201020220207\u201000097"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.42070"}],"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.63953","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T05:34:56Z","timestamp":1765517696000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.63953"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,6]]},"references-count":31,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1002\/ajmg.a.63953"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.63953","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,6]]},"assertion":[{"value":"2024-09-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e63953"}}