{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T14:01:43Z","timestamp":1781186503151,"version":"3.54.1"},"reference-count":8,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,8,9]],"date-time":"2021-08-09T00:00:00Z","timestamp":1628467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["303375\/2019\u20101"],"award-info":[{"award-number":["303375\/2019\u20101"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"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":["Clinical Genetics"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Congenital limb deficiency (CLD), one of the most common congenital anomalies, is characterized by hypoplasia\/aplasia of one or more limb bones and can be isolated or syndromic. The etiology in CLD is heterogeneous, including environmental and genetic factors. A fraction remains with no etiological factor identified. We report the study of 44 Brazilian individuals presenting isolated or syndromic CLD, mainly with longitudinal defects. Genetic investigation included particularly next\u2010generation sequencing (NGS) and\/or chromosomal microarray. The overall diagnostic yield was 45.7%, ranging from 60.9% in the syndromic to 16.7% in the non\u2010syndromic group. In TAR syndrome, a common variant in 3\u00b4UTR of\n                    <jats:italic>RBM8A<\/jats:italic>\n                    , in trans with 1q21.1 microdeletion, was detected, corroborating the importance of this recently reported variant in individuals of African ancestry. NGS established a diagnosis in three individuals in syndromes recently reported or still under delineation (an acrofacial dysostosis, Coats plus and Verheij syndromes), suggesting a broader phenotypic spectrum in these disorders. Although a low rate of molecular detection in non\u2010syndromic forms was observed, it is still possible that variants in non\u2010coding regions and small CNVs, not detected by the techniques applied in this study, could play a role in the etiology of CLD.\n                  <\/jats:p>","DOI":"10.1111\/cge.14041","type":"journal-article","created":{"date-parts":[[2021,8,2]],"date-time":"2021-08-02T22:35:25Z","timestamp":1627943725000},"page":"615-623","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Congenital limb deficiency: Genetic investigation of 44 individuals presenting mainly longitudinal defects in isolated or syndromic forms"],"prefix":"10.1111","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0822-2153","authenticated-orcid":false,"given":"Let\u00edcia Alves","family":"da Rocha","sequence":"first","affiliation":[{"name":"Genetics Unit, Instituto da Crian\u00e7a Hospital das Cl\u00ednicas, Faculdade de Medicina, Universidade de S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8649-976X","authenticated-orcid":false,"given":"Lucas Vieira Lacerda","family":"Pires","sequence":"additional","affiliation":[{"name":"Genetics Unit, Instituto da Crian\u00e7a Hospital das Cl\u00ednicas, 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":"Genetics Unit, Instituto da Crian\u00e7a Hospital das Cl\u00ednicas, Faculdade de Medicina, Universidade de S\u00e3o Paulo  S\u00e3o Paulo Brazil"},{"name":"Human Genome and Stem\u2010Cell Research Center, Departamento de Gen\u00e9tica e Biologia Evolutiva, Instituto de Bioci\u00eancias Universidade de S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Ricardo","family":"Magliocco Ceroni","sequence":"additional","affiliation":[{"name":"Genetics Unit, Instituto da Crian\u00e7a Hospital das Cl\u00ednicas, Faculdade de Medicina, Universidade de S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel Sayuri","family":"Honjo","sequence":"additional","affiliation":[{"name":"Genetics Unit, Instituto da Crian\u00e7a Hospital das Cl\u00ednicas, Faculdade de Medicina, Universidade de S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgard","family":"de Novaes Fran\u00e7a Bisneto","sequence":"additional","affiliation":[{"name":"Orthopedics and Traumatology Institute Hospital das Cl\u00ednicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiz Ant\u00f4nio Nunes","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Radiology, Instituto da Crian\u00e7a Hospital das Cl\u00ednicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Rosenberg","sequence":"additional","affiliation":[{"name":"Human Genome and Stem\u2010Cell Research Center, Departamento de Gen\u00e9tica e Biologia Evolutiva, Instituto de Bioci\u00eancias Universidade de S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Cristina Victorino","family":"Krepischi","sequence":"additional","affiliation":[{"name":"Human Genome and Stem\u2010Cell Research Center, Departamento de Gen\u00e9tica e Biologia Evolutiva, Instituto de Bioci\u00eancias Universidade de S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9248-3008","authenticated-orcid":false,"given":"Maria Rita","family":"Passos\u2010Bueno","sequence":"additional","affiliation":[{"name":"Human Genome and Stem\u2010Cell Research Center, Departamento de Gen\u00e9tica e Biologia Evolutiva, Instituto de Bioci\u00eancias Universidade de S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong Ae","family":"Kim","sequence":"additional","affiliation":[{"name":"Genetics Unit, Instituto da Crian\u00e7a Hospital das Cl\u00ednicas, Faculdade de Medicina, Universidade de S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4701-6777","authenticated-orcid":false,"given":"D\u00e9bora Romeo","family":"Bertola","sequence":"additional","affiliation":[{"name":"Genetics Unit, Instituto da Crian\u00e7a Hospital das Cl\u00ednicas, Faculdade de Medicina, Universidade de S\u00e3o Paulo  S\u00e3o Paulo Brazil"},{"name":"Human Genome and Stem\u2010Cell Research Center, Departamento de Gen\u00e9tica e Biologia Evolutiva, Instituto de Bioci\u00eancias Universidade de S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,8,9]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61875"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40246-015-0031-5"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23912"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37240"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2012.16"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.24021"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2015.03.011"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.1084"}],"container-title":["Clinical 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