{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T08:31:09Z","timestamp":1791361869413,"version":"4.3.1"},"reference-count":32,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T00:00:00Z","timestamp":1719273600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2013\/08028\u20101"],"award-info":[{"award-number":["2013\/08028\u20101"]}],"id":[{"id":"10.13039\/501100001807","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":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Low\u2010pass whole genome sequencing (LP\u2010WGS) has been applied as alternative method to detect copy number variants (CNVs) in the clinical setting. Compared with chromosomal microarray analysis (CMA), the sequencing\u2010based approach provides a similar resolution of CNV detection at a lower cost. In this study, we assessed the efficiency and reliability of LP\u2010WGS as a more affordable alternative to CMA. A total of 1363 patients with unexplained neurodevelopmental delay\/intellectual disability, autism spectrum disorders, and\/or multiple congenital anomalies were enrolled. Those patients were referred from 15 nonprofit organizations and university centers located in different states in Brazil. The analysis of LP\u2010WGS at 1x coverage (&gt;50kb) revealed a positive testing result in 22% of the cases (304\/1363), in which 219 and 85 correspond to pathogenic\/likely pathogenic (P\/LP) CNVs and variants of uncertain significance (VUS), respectively. The 16% (219\/1363) diagnostic yield observed in our cohort is comparable to the 15%\u201320% reported for CMA in the literature. The use of commercial software, as demonstrated in this study, simplifies the implementation of the test in clinical settings. Particularly for countries like Brazil, where the cost of CMA presents a substantial barrier to most of the population, LP\u2010WGS emerges as a cost\u2010effective alternative for investigating copy number changes in cytogenetics.<\/jats:p>","DOI":"10.1002\/ajmg.a.63802","type":"journal-article","created":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T13:01:33Z","timestamp":1719320493000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Low\u2010pass whole genome sequencing as a cost\u2010effective alternative to chromosomal microarray analysis for low\u2010 and middle\u2010income countries"],"prefix":"10.1002","volume":"194","author":[{"given":"Patricia C.","family":"Mazzonetto","sequence":"first","affiliation":[{"name":"The Human Genome and Stem Cell Research Center, Department of Genetics and Evolutionary Biology Institute of Biosciences, University of S\u00e3o Paulo  S\u00e3o Paulo Brazil"},{"name":"Diagn\u00f3sticos da Am\u00e9rica S.A., DASA  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5930-5269","authenticated-orcid":false,"given":"Darine","family":"Villela","sequence":"additional","affiliation":[{"name":"Diagn\u00f3sticos da Am\u00e9rica S.A., DASA  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana C. V.","family":"Krepischi","sequence":"additional","affiliation":[{"name":"The Human Genome and Stem Cell Research Center, Department of Genetics and Evolutionary Biology Institute of Biosciences, University of S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo M.","family":"Pierry","sequence":"additional","affiliation":[{"name":"Diagn\u00f3sticos da Am\u00e9rica S.A., DASA  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriano","family":"Bonaldi","sequence":"additional","affiliation":[{"name":"Diagn\u00f3sticos da Am\u00e9rica S.A., DASA  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiz Gustavo D.","family":"Almeida","sequence":"additional","affiliation":[{"name":"Diagn\u00f3sticos da Am\u00e9rica S.A., DASA  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo G.","family":"Paula","sequence":"additional","affiliation":[{"name":"Diagn\u00f3sticos da Am\u00e9rica S.A., DASA  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matheus Carvalho","family":"B\u00fcrger","sequence":"additional","affiliation":[{"name":"Diagn\u00f3sticos da Am\u00e9rica S.A., DASA  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Gabriela","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Diagn\u00f3sticos da Am\u00e9rica S.A., DASA  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo G. G.","family":"Fonseca","sequence":"additional","affiliation":[{"name":"Diagn\u00f3sticos da Am\u00e9rica S.A., DASA  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Giugliani","sequence":"additional","affiliation":[{"name":"Diagn\u00f3sticos da Am\u00e9rica S.A., DASA  S\u00e3o Paulo Brazil"},{"name":"Casa dos Raros \u2010 House of Rares, Centro de Aten\u00e7\u00e3o Integral e Treinamento em Doen\u00e7as Raras  Porto Alegre Brazil"},{"name":"INAGEMP, Instituto Nacional de Gen\u00e9tica M\u00e9dica Populacional  Porto Alegre Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6397-1301","authenticated-orcid":false,"given":"Mariluce","family":"Riegel\u2010Giugliani","sequence":"additional","affiliation":[{"name":"Casa dos Raros \u2010 House of Rares, Centro de Aten\u00e7\u00e3o Integral e Treinamento em Doen\u00e7as Raras  Porto Alegre Brazil"},{"name":"INAGEMP, Instituto Nacional de Gen\u00e9tica M\u00e9dica Populacional  Porto Alegre Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00e9bora","family":"Bertola","sequence":"additional","affiliation":[{"name":"Instituto da Crian\u00e7a, Faculdade de Medicina, Universidade de S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilherme Lopes","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Diagn\u00f3sticos da Am\u00e9rica S.A., DASA  S\u00e3o Paulo Brazil"},{"name":"Instituto da Crian\u00e7a, Faculdade de Medicina, Universidade de S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Rita","family":"Passos\u2010Bueno","sequence":"additional","affiliation":[{"name":"The Human Genome and Stem Cell Research Center, Department of Genetics and Evolutionary Biology Institute of Biosciences, University of S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele da Silva","family":"Campos","sequence":"additional","affiliation":[{"name":"The Human Genome and Stem Cell Research Center, Department of Genetics and Evolutionary Biology Institute of Biosciences, University of S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Claudia Dantas","family":"Machado","sequence":"additional","affiliation":[{"name":"The Human Genome and Stem Cell Research Center, Department of Genetics and Evolutionary Biology Institute of Biosciences, University of S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6161-0510","authenticated-orcid":false,"given":"Juliana F.","family":"Mazzeu","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina Universidade de Bras\u00edlia  Bras\u00edlia Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Perrone","sequence":"additional","affiliation":[{"name":"Departamento de Morfologia e Gen\u00e9tica Universidade Federal de S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roseli M.","family":"Zechi\u2010Ceide","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics and Molecular Biology Hospital for Rehabilitation of Craniofacial Anomalies, University of S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0252-5452","authenticated-orcid":false,"given":"Nancy M.","family":"Kokitsu\u2010Nakata","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics and Molecular Biology Hospital for Rehabilitation of Craniofacial Anomalies, University of S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4027-8341","authenticated-orcid":false,"given":"T\u00e1rsis Paiva","family":"Vieira","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine \u2013 Medical Genetics and Genomic Medicine School of Medical Sciences, University of Campinas  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5148-3063","authenticated-orcid":false,"given":"Carlos Eduardo","family":"Steiner","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine \u2013 Medical Genetics and Genomic Medicine School of Medical Sciences, University of Campinas  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera L\u00facia","family":"Gil\u2010da\u2010Silva\u2010Lopes","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine \u2013 Medical Genetics and Genomic Medicine School of Medical Sciences, University of Campinas  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela Koeller Rodrigues","family":"Vieira","sequence":"additional","affiliation":[{"name":"Municipal Secretary of Health of Angra dos Reis  Rio de Janeiro Brazil"},{"name":"National Institute of Women, Children and Adolescents Health Fernandes Figueira\/Oswaldo Cruz Foundation (IFF\/FIOCRUZ)  Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Boy","sequence":"additional","affiliation":[{"name":"State University of Rio de Janeiro  Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o Monteiro","family":"de Pina\u2010Neto","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina de Ribeir\u00e3o Preto Universidade de S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristovam","family":"Scapulatempo\u2010Neto","sequence":"additional","affiliation":[{"name":"Diagn\u00f3sticos da Am\u00e9rica S.A., DASA  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda","family":"Milanezi","sequence":"additional","affiliation":[{"name":"Diagn\u00f3sticos da Am\u00e9rica S.A., DASA  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Rosenberg","sequence":"additional","affiliation":[{"name":"The Human Genome and Stem Cell Research Center, Department of Genetics and Evolutionary Biology Institute of Biosciences, University of S\u00e3o Paulo  S\u00e3o Paulo Brazil"},{"name":"Diagn\u00f3sticos da Am\u00e9rica S.A., DASA  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,6,25]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2014-102588"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg.2015.25"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)31243-7"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2020.03.008"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.806"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-021-01128-7"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/cphg.43"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.199"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-016-0375-z"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gim.2022.04.009"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-19274-6"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdy476"},{"key":"e_1_2_11_14_1","first-page":"22","article-title":"Brazil's mixed public and private hospital system","volume":"51","author":"Lewis M.","year":"2015","journal-title":"World Hospitals and Health Services"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.120086"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9525(98)01555-8"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/ahg.12532"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2010.04.006"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1177\/15353702211040046"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.24441"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamahealthforum.2022.0603"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-019-0686-8"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000031431.81555.16"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-018-0244-x"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-019-0554-6"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aab3761"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-022-01185-9"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2017.08.020"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/ahg.12402"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-019"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2014-102497"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics12051098"}],"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.63802","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T09:42:05Z","timestamp":1733132525000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.63802"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,25]]},"references-count":32,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2024,11]]}},"alternative-id":["10.1002\/ajmg.a.63802"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.63802","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,25]]},"assertion":[{"value":"2024-04-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e63802"}}