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Congenital heart disease (CHD) is one of the most relevant phenotypes in the syndrome and copy number variants (CNVs) outside the 22q11.2 region could play a role in its variable expressivity. Since those described loci account for a small proportion of the variability, the CNV analysis in new cohorts from different ancestry\u2010based populations constitutes a valuable resource to identify a wider range of modifiers. We performed SNP\u2010array in 117 Brazilian patients with 22q11.2DS, with and without CHD, and leveraged genome\u2010wide CNV analysis. After quality control, we selected 50 CNVs in 38 patients for downstream analysis. CNVs' genetic content and implicated biological pathways were compared between patients with and without CHD. CNV\u2010affected genes in patients with CHD were enriched for several functional terms related to ubiquitination, transcription factor binding sites and miRNA targets, highlighting the complexity of the phenotype's expressivity. Cardiac\u2010related genes were identified in both groups of patients suggesting that increasing risk and protective mechanisms could be involved. These genes and enriched pathways could indicate new modifiers to the cardiac phenotype in 22q11.2DS patients.<\/jats:p>","DOI":"10.1002\/ajmg.a.63145","type":"journal-article","created":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T06:58:31Z","timestamp":1675839511000},"page":"1273-1281","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Phenotypic heterogeneity in 22q11.2 deletion syndrome: <scp>Copy\u00a0Number\u00a0Variants<\/scp> as genetic modifiers for congenital heart disease in a Brazilian cohort"],"prefix":"10.1002","volume":"191","author":[{"given":"M.","family":"Zamariolli","sequence":"first","affiliation":[{"name":"Genetic Division Universidade Federal de S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. G.","family":"Dantas","sequence":"additional","affiliation":[{"name":"Genetic Division Universidade Federal de S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N.","family":"Nunes","sequence":"additional","affiliation":[{"name":"Genetic Division Universidade Federal de S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Moys\u00e9s\u2010Oliveira","sequence":"additional","affiliation":[{"name":"Sleep Institute  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I. C.","family":"Sgardioli","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Area of Medical Genetics and Genomic Medicine Universidade Estadual de Campinas  Campinas Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. C. 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