{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T12:13:13Z","timestamp":1756383193803,"version":"3.37.3"},"reference-count":59,"publisher":"Wiley","license":[{"start":{"date-parts":[[2024,3,30]],"date-time":"2024-03-30T00:00:00Z","timestamp":1711756800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2019\/21644-0","001","309782\/2020-1"],"award-info":[{"award-number":["2019\/21644-0","001","309782\/2020-1"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["2019\/21644-0","001","309782\/2020-1"],"award-info":[{"award-number":["2019\/21644-0","001","309782\/2020-1"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["2019\/21644-0","001","309782\/2020-1"],"award-info":[{"award-number":["2019\/21644-0","001","309782\/2020-1"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genetics Research"],"published-print":{"date-parts":[[2024,3,30]]},"abstract":"<jats:p>22q11.2 deletion syndrome (22q11.2DS) is a microdeletion syndrome with a broad and heterogeneous phenotype, even though most of the deletions present similar sizes, involving \u223c3\u2009Mb of DNA. In a relatively large population of a Brazilian 22q11.2DS cohort (60 patients), we investigated genetic variants that could act as genetic modifiers and contribute to the phenotypic heterogeneity, using a targeted NGS (Next Generation Sequencing) with a specific Ion AmpliSeq panel to sequence nine candidate genes (CRKL, MAPK1, HIRA, TANGO2, PI4KA, HDAC1, ZDHHC8, ZFPM2, and JAM3), mapped in and outside the 22q11.2 hemizygous deleted region. In silico prediction was performed, and the whole-genome sequencing annotation analysis package (WGSA) was used to predict the possible pathogenic effect of single nucleotide variants (SNVs). For the in silico prediction of the indels, we used the genomic variants filtered by a deep learning model in NGS (GARFIELD-NGS). We identified six variants, 4 SNVs and 2 indels, in MAPK1, JAM3, and ZFPM2 genes with possibly synergistic deleterious effects in the context of the 22q11.2 deletion. Our results provide the opportunity for the discovery of the co-occurrence of genetic variants with 22q11.2 deletions, which may influence the patients\u00b4 phenotype.<\/jats:p>","DOI":"10.1155\/2024\/5549592","type":"journal-article","created":{"date-parts":[[2024,3,30]],"date-time":"2024-03-30T18:20:09Z","timestamp":1711822809000},"page":"1-9","source":"Crossref","is-referenced-by-count":1,"title":["Variants in Candidate Genes for Phenotype Heterogeneity in Patients with the 22q11.2 Deletion Syndrome"],"prefix":"10.1155","volume":"2024","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7247-4745","authenticated-orcid":true,"given":"Natalia","family":"Nunes","sequence":"first","affiliation":[{"name":"Genetics Division, Department of Morphology and Genetics, Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1230-1113","authenticated-orcid":true,"given":"Beatriz","family":"Carvalho Nunes","sequence":"additional","affiliation":[{"name":"Genetics Division, Department of Morphology and Genetics, Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3125-1948","authenticated-orcid":true,"given":"Mal\u00fa","family":"Zamariolli","sequence":"additional","affiliation":[{"name":"Genetics Division, Department of Morphology and Genetics, Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6589-2367","authenticated-orcid":true,"given":"Diogo","family":"Cordeiro de Queiroz Soares","sequence":"additional","affiliation":[{"name":"Genetics Unit, Instituto da Crian\u00e7a, Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8181-3884","authenticated-orcid":true,"given":"Leonardo","family":"Caires dos Santos","sequence":"additional","affiliation":[{"name":"Genetics Division, Department of Morphology and Genetics, Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0594-6762","authenticated-orcid":true,"given":"Anelisa","family":"Gollo Dantas","sequence":"additional","affiliation":[{"name":"Genetics Division, Department of Morphology and Genetics, Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4954-8766","authenticated-orcid":true,"given":"Vera","family":"Ayres Meloni","sequence":"additional","affiliation":[{"name":"Genetics Division, Department of Morphology and Genetics, Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2419-4351","authenticated-orcid":true,"given":"Sintia","family":"Iole Belangero","sequence":"additional","affiliation":[{"name":"Genetics Division, Department of Morphology and Genetics, Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1288-0554","authenticated-orcid":true,"given":"Vera L\u00facia","family":"Gil-Da-Silva-Lopes","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, School of Medical Sciences, University of Campinas, Campinas, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1754-1300","authenticated-orcid":true,"given":"Chong","family":"Ae Kim","sequence":"additional","affiliation":[{"name":"Genetics Unit, Instituto da Crian\u00e7a, Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4344-9698","authenticated-orcid":true,"given":"Maria Isabel","family":"Melaragno","sequence":"additional","affiliation":[{"name":"Genetics Division, Department of Morphology and Genetics, Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2015.71"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38199"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31774"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.40494"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.40504"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2010.04.011"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38662"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-018-01967-6"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.1002\/ddrr.4"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2013.07.019"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-01896-w"},{"key":"12","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10261"},{"key":"13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2015.01.011"},{"key":"14","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2015.10.051"},{"key":"15","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.4.489"},{"key":"16","doi-asserted-by":"publisher","DOI":"10.1007\/s00406-010-0098-x"},{"key":"17","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp190"},{"key":"18","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37614"},{"key":"19","doi-asserted-by":"publisher","DOI":"10.1159\/000207515"},{"key":"20","doi-asserted-by":"publisher","DOI":"10.1100\/tsw.2006.317"},{"key":"21","doi-asserted-by":"publisher","DOI":"10.1038\/35065105"},{"key":"22","doi-asserted-by":"publisher","DOI":"10.1038\/hgv.2015.65"},{"key":"23","doi-asserted-by":"publisher","DOI":"10.1016\/j.eurpsy.2004.06.007"},{"key":"24","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4002080"},{"key":"25","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm330"},{"key":"26","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx771"},{"key":"27","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddw221"},{"key":"28","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-015-1623-9"},{"key":"29","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20604"},{"key":"30","doi-asserted-by":"publisher","DOI":"10.1007\/s00246-018-1806-y"},{"key":"31","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38597"},{"key":"32","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2019.11.010"},{"article-title":"PubMed","year":"2023","author":"PubMed","key":"33"},{"article-title":"GeneCards","year":"2023","author":"GeneCards","key":"34"},{"article-title":"UCSC Genome Browser","year":"2023","author":"UCSC Genome Browser","key":"35"},{"article-title":"Online mendelian inheritance in man","year":"2023","author":"Online Mendelian Inheritance in Man","key":"36"},{"article-title":"Ion AmpliSeqTM Designer","year":"2023","author":"Ion","key":"37"},{"key":"38","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2014.03.032"},{"key":"39","doi-asserted-by":"publisher","DOI":"10.1038\/nature19057"},{"key":"40","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28648-3"},{"key":"41","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty303"},{"key":"42","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2015-103423"},{"key":"43","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-016-3094-3"},{"key":"44","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks596"},{"key":"45","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btm091"},{"article-title":"OligoAnalyzer","year":"2023","author":"OligoAnalyzer","key":"46"},{"key":"47","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2012.0362"},{"key":"48","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2019.00806"},{"key":"49","doi-asserted-by":"publisher","DOI":"10.1002\/dvg.23333"},{"key":"50","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.19.6.4495"},{"key":"51","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-4-9"},{"key":"52","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32913"},{"key":"53","doi-asserted-by":"publisher","DOI":"10.1080\/17446651.2017.1312341"},{"key":"54","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.01.007"},{"key":"55","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgw126"},{"key":"56","doi-asserted-by":"publisher","DOI":"10.1006\/geno.2002.6742"},{"key":"57","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-74793-4"},{"key":"58","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2018.17040467"},{"key":"59","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23220"}],"container-title":["Genetics Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/gr\/2024\/5549592.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/gr\/2024\/5549592.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/gr\/2024\/5549592.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,30]],"date-time":"2024-03-30T18:20:16Z","timestamp":1711822816000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.hindawi.com\/journals\/gr\/2024\/5549592\/"}},"subtitle":[],"editor":[{"given":"Xiaoye","family":"Jin","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2024,3,30]]},"references-count":59,"alternative-id":["5549592","5549592"],"URL":"https:\/\/doi.org\/10.1155\/2024\/5549592","relation":{},"ISSN":["1469-5073"],"issn-type":[{"type":"electronic","value":"1469-5073"}],"subject":[],"published":{"date-parts":[[2024,3,30]]}}}