{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T17:37:29Z","timestamp":1791999449221,"version":"4.4.0"},"reference-count":17,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2017,6,20]],"date-time":"2017-06-20T00:00:00Z","timestamp":1497916800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:sec><jats:label\/><jats:p>We describe monozygotic twin girls with genetic variation at two separate loci resulting in a blended phenotype of Prader\u2013Willi syndrome and Pitt\u2013Hopkins syndrome. These girls were diagnosed in early infancy with Prader\u2013Willi syndrome, but developed an atypical phenotype, with apparent intellectual deficiency and lack of obesity. Array\u2010comparative genomic hybridization confirmed a de novo paternal deletion of the 15q11.2q13 region and exome sequencing identified a second mutational event in both girls, which was a novel variant c.145+1G&gt;A affecting a <jats:italic>TCF4<\/jats:italic> canonical splicing site inherited from the mosaic mother. RNA studies showed that the variant abolished the donor splicing site, which was accompanied by activation of an alternative non\u2010canonical splicing\u2010site which then predicts a premature stop codon in the following exon. Clinical re\u2010evaluation of the twins indicated that both variants are likely contributing to the more severe phenotypic presentation. Our data show that atypical clinical presentations may actually be the expression of blended clinical phenotypes arising from independent pathogenic events at two loci.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.38315","type":"journal-article","created":{"date-parts":[[2017,6,20]],"date-time":"2017-06-20T11:50:50Z","timestamp":1497959450000},"page":"2451-2455","source":"Crossref","is-referenced-by-count":25,"title":["Dual molecular diagnosis contributes to atypical Prader\u2013Willi phenotype in monozygotic twins"],"prefix":"10.1002","volume":"173","author":[{"given":"Fernanda S.","family":"Jehee","sequence":"first","affiliation":[{"name":"Instituto de Ensino e Pesquisa Santa Casa de Belo Horizonte Belo Horizonte Minas Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valdirene T.","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Instituto de Ensino e Pesquisa Santa Casa de Belo Horizonte Belo Horizonte Minas Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana","family":"Gurgel\u2010Giannetti","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina da Universidade Federal de Minas Gerais Belo Horizonte Minas Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafaella X.","family":"Pietra","sequence":"additional","affiliation":[{"name":"Instituto de Ensino e Pesquisa Santa Casa de Belo Horizonte Belo Horizonte Minas Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando V. M.","family":"Rubatino","sequence":"additional","affiliation":[{"name":"Instituto de Ensino e Pesquisa Santa Casa de Belo Horizonte Belo Horizonte Minas Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nat\u00e1lia V.","family":"Carobin","sequence":"additional","affiliation":[{"name":"Instituto de Ensino e Pesquisa Santa Casa de Belo Horizonte Belo Horizonte Minas Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabrielle S.","family":"Vianna","sequence":"additional","affiliation":[{"name":"Instituto de Ensino e Pesquisa Santa Casa de Belo Horizonte Belo Horizonte Minas Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana L.","family":"de Freitas","sequence":"additional","affiliation":[{"name":"Instituto de Ensino e Pesquisa Santa Casa de Belo Horizonte Belo Horizonte Minas Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karla S.","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Instituto de Ensino e Pesquisa Santa Casa de Belo Horizonte Belo Horizonte Minas Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz S. V.","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina da Universidade Federal de Minas Gerais Belo Horizonte Minas Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hennie T.","family":"Br\u00fcggenwirth","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Erasmus University Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roza","family":"Ali\u2010Amin","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Erasmus University Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Baylor\u2010Hopkins Center for Mendelian Genomics","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janson J.","family":"White","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeynep C.","family":"Akdemir","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shalini N.","family":"Jhangiani","sequence":"additional","affiliation":[{"name":"Human Genome Sequencing Center Baylor College of Medicine Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Gibbs","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine Houston Texas"},{"name":"Human Genome Sequencing Center Baylor College of Medicine Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R.","family":"Lupski","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine Houston Texas"},{"name":"Human Genome Sequencing Center Baylor College of Medicine Houston Texas"},{"name":"Texas Children's Hospital Houston Texas"},{"name":"Department of Pediatrics Baylor College of Medicine Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica C.","family":"Varela","sequence":"additional","affiliation":[{"name":"Department of Genetics and Evolutionary Biology, Institute of Biosciences University of S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9lia","family":"Koiffmann","sequence":"additional","affiliation":[{"name":"Department of Genetics and Evolutionary Biology, Institute of Biosciences University of S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Rosenberg","sequence":"additional","affiliation":[{"name":"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\/0000-0002-2090-298X","authenticated-orcid":false,"given":"Cl\u00e1udia M. 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