{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T12:24:34Z","timestamp":1789647874137,"version":"4.0.0"},"reference-count":102,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T00:00:00Z","timestamp":1620172800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/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":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Phelan\u2010McDermid syndrome (PMS, OMIM #606232), also known as chromosome 22q13 deletion syndrome, is a rare genetic disorder characterized by intellectual disability, hypotonia, delayed or absent speech, motor impairment, autism spectrum disorder, behavioral anomalies, and minor aspecific dysmorphic features. Haploinsufficiency of <jats:italic>SHANK3<\/jats:italic>, due to intragenic deletions or point mutations, is sufficient to cause many neurobehavioral features of PMS. However, several additional genes located within larger 22q13 deletions can contribute to the great interindividual variability observed in the PMS phenotype. This review summarizes the phenotypic contributions predicted for 213 genes distributed along the largest 22q13.2\u2010q13.33 terminal deletion detected in our sample of 63 PMS patients by array\u2010CGH analysis, spanning 9.08\u2009Mb. Genes have been grouped into four categories: (1) genes causing human diseases with an autosomal dominant mechanism, or (2) with an autosomal recessive mechanism; (3) morphogenetically relevant genes, either involved in human diseases with additive co\u2010dominant, polygenic, and\/or multifactorial mechanisms, or implicated in animal models but not yet documented in human pathology; (4) protein coding genes either functionally nonrelevant, with unknown function, or pathogenic through mechanisms other than haploinsufficiency; piRNAs, noncoding RNAs, miRNAs, novel transcripts and pseudogenes. Our aim is to understand genotype\u2013phenotype correlations in PMS patients and to provide clinicians with a conceptual framework to promote evidence\u2010based genetic work\u2010ups, clinical assessments, and therapeutic interventions.<\/jats:p>","DOI":"10.1002\/ajmg.a.62222","type":"journal-article","created":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T14:59:46Z","timestamp":1620226786000},"page":"2211-2233","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Genotype\u2013phenotype correlation in <scp>Phelan\u2010McDermid<\/scp> syndrome: A comprehensive review of chromosome 22q13 deleted genes"],"prefix":"10.1002","volume":"185","author":[{"given":"Arianna","family":"Ricciardello","sequence":"first","affiliation":[{"name":"Interdepartmental Program \u201cAutism 0\u201090\u201d \u201cGaetano Martino\u201d University Hospital, University of Messina  Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasquale","family":"Tomaiuolo","sequence":"additional","affiliation":[{"name":"Interdepartmental Program \u201cAutism 0\u201090\u201d \u201cGaetano Martino\u201d University Hospital, University of Messina  Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8910-4479","authenticated-orcid":false,"given":"Antonio M.","family":"Persico","sequence":"additional","affiliation":[{"name":"Interdepartmental Program \u201cAutism 0\u201090\u201d \u201cGaetano Martino\u201d University Hospital, University of Messina  Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,5,5]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35700"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2018.08.013"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-019-1220-4"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13451"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2013.210"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002173"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2017.236"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2016.07.011"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2019.09.029"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.22293"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2009.40"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2008.04.029"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13229-018-0205-9"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5381-06.2007"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33253"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36513"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24826"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glx160"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/13816810.2019.1692361"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.3233\/TRD-160005"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13419"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4710-06.2007"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep19544"},{"key":"e_1_2_9_25_1","first-page":"117","article-title":"Mitochondrial infantile liver disease due to TRMU gene mutations: Three new cases","volume":"11","author":"Gaignard P.","year":"2013","journal-title":"Journal of Inherited Metabolic Diseases Reports"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.117.077560"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1161-10.2010"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13523"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000005334"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13506"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.119.088047"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10815-016-0863-5"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2013.508"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2004090776"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.05.015"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2004.00703.x"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2017.05.016"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2016.11.035"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.02.049"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2014.17"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1186\/s11689-020-9309-6"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1186\/1866-1955-6-39"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty897"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.21.20.7025-7034.2001"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexmp.2018.01.001"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.41.29510"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2015.02.002"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-016-0505-1"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.14419"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3122"},{"key":"e_1_2_9_51_1","first-page":"1993","volume-title":"GeneReviews\u00ae [Internet]","author":"Matsuura T.","year":"2002"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2018.06.008"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-017-0085-3"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2008.08.029"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.05.010"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-017-0042-x"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.06.3701"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.31023"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2018.00669"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38559"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2018.12.011"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12227"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diff.2010.10.001"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2008.07017.x"},{"key":"e_1_2_9_65_1","volume-title":"StatPearls [internet]","author":"Pescador Ruschel M. A.","year":"2020"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2010.193"},{"issue":"3","key":"e_1_2_9_67_1","first-page":"186","article-title":"The 22q13.3 deletion syndrome (Phelan\u2010McDermid syndrome)","volume":"2","author":"Phelan K.","year":"2012","journal-title":"Molecular Syndromology"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2013.05.007"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20160686"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2017.09.001"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-34729-5"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nlm.2017.03.009"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2010.08.041"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-006-0199-9"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2017.03.010"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M006978200"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.26508\/lsa.201800094"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhepr.2019.05.007"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-014-1423-7"},{"key":"e_1_2_9_80_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2013.144"},{"key":"e_1_2_9_81_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2011-100225"},{"key":"e_1_2_9_82_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20092134"},{"key":"e_1_2_9_83_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2006.02.177"},{"key":"e_1_2_9_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2006.08.030"},{"key":"e_1_2_9_85_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21072613"},{"key":"e_1_2_9_86_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36358"},{"key":"e_1_2_9_87_1","doi-asserted-by":"publisher","DOI":"10.1186\/2040-2392-4-18"},{"key":"e_1_2_9_88_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-25280-4"},{"key":"e_1_2_9_89_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2019.08.007"},{"key":"e_1_2_9_90_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-019-0623-0"},{"key":"e_1_2_9_91_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-019-1364-z"},{"key":"e_1_2_9_92_1","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2018.0033"},{"key":"e_1_2_9_93_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-019-0454-9"},{"key":"e_1_2_9_94_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.04.005"},{"key":"e_1_2_9_95_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2011.089995"},{"key":"e_1_2_9_96_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M064022"},{"key":"e_1_2_9_97_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-7091-0932-8_2"},{"key":"e_1_2_9_98_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI87997"},{"key":"e_1_2_9_99_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-5618.2005.00184.x"},{"key":"e_1_2_9_100_1","doi-asserted-by":"publisher","DOI":"10.1002\/jez.b.21260"},{"key":"e_1_2_9_101_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2016-1487"},{"key":"e_1_2_9_102_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfp637"},{"key":"e_1_2_9_103_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2010.01598.x"}],"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.62222","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.62222","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62222","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T08:44:54Z","timestamp":1692953094000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.62222"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,5]]},"references-count":102,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2021,7]]}},"alternative-id":["10.1002\/ajmg.a.62222"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.62222","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,5]]},"assertion":[{"value":"2020-10-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-04-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}