{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T09:46:40Z","timestamp":1785836800827,"version":"3.56.0"},"reference-count":21,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The transformation\/transcription domain\u2010associated protein (\n                    <jats:italic>TRRAP<\/jats:italic>\n                    ) gene encodes a large multidomain protein, a member of the phosphatidylinositol 3\u2010kinase\u2010related kinase (PIKK) family. TRRAP is a component of the histone acetyltransferase (HAT) complex, and it plays an important role in gene transcription, DNA repair, and cell\u2010cycle regulation. Heterozygous missense variants in the\n                    <jats:italic>TRRAP<\/jats:italic>\n                    gene have been associated with a multiple system condition known as developmental delay with or without dysmorphic facies and autism (DEDDFA; OMIM #618454), hearing loss, and different types of cancer. Strong genotype\u2013phenotype correlation has been observed in DEDDFA, where missense variants located in the clustering between residues 1031\u20131159 result in more pronounced facial anomalies associated with a variable degree of intellectual disability. Here, we report two Brazilian females with syndromic orofacial cleft, presenting very similar atypical facial phenotypes and multisystem anomalies. Both had a severe phenotype with global developmental delay, ranging from moderate to severe, and one of them had a severe behavior disorder associated with non\u2010verbal autism while the other had inguinal cancer. Next\u2010generation sequencing showed that both displayed heterozygous missense variants in the\n                    <jats:italic>TRRAP<\/jats:italic>\n                    gene, clustering at the 1031\u20101159 amino acid residues. These cases reinforce the genotype\u2013phenotype correlation of variants in the\n                    <jats:italic>TRRAP<\/jats:italic>\n                    gene with a possible new domain in the cluster 1031\u20101159.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.70155","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T06:31:04Z","timestamp":1775716264000},"page":"2099-2105","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Long\u2010Term Follow Up of Two Patients With Variants in the Cluster 1031\u20101159 of\n                    <i>TRRAP<\/i>\n                    Gene: Expanding the Phenotype of Developmental Delay With or Without Dysmorphic Facies and Autism"],"prefix":"10.1002","volume":"200","author":[{"given":"Roseli Maria","family":"Zechi\u2010Ceide","sequence":"first","affiliation":[{"name":"Hospital for Rehabilitation of Craniofacial Anomalies, University of S\u00e3o Paulo  Bauru Brazil"},{"name":"Bauru Medical School, University of S\u00e3o Paulo  Bauru Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinicius Contrucci Dantas","family":"Segarra","sequence":"additional","affiliation":[{"name":"Hospital for Rehabilitation of Craniofacial Anomalies, University of S\u00e3o Paulo  Bauru Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siulan","family":"Vendramini\u2010Pittoli","sequence":"additional","affiliation":[{"name":"Hospital for Rehabilitation of Craniofacial Anomalies, University of S\u00e3o Paulo  Bauru Brazil"},{"name":"Bauru Medical School, University of S\u00e3o Paulo  Bauru Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4355-6677","authenticated-orcid":false,"given":"Henrique Regonaschi","family":"Serigatto","sequence":"additional","affiliation":[{"name":"Hospital for Rehabilitation of Craniofacial Anomalies, University of S\u00e3o Paulo  Bauru Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiza","family":"Virmond","sequence":"additional","affiliation":[{"name":"Hospital for Rehabilitation of Craniofacial Anomalies, University of S\u00e3o Paulo  Bauru Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heloisa Marcelina","family":"da Cunha Palhares","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Pediatric Endocrinology Service, Federal University of Tri\u00e2ngulo Mineiro  Uberaba Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda","family":"Jehee","sequence":"additional","affiliation":[{"name":"Department of Genetics Utrecht University Medical Center  Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Cristina Victorino","family":"Krepischi","sequence":"additional","affiliation":[{"name":"Human Genome and Stem Cell Research Center, 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":"Human Genome and Stem Cell Research Center, Institute of Biosciences, University of S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Henrique Paiva","family":"Grangeiro","sequence":"additional","affiliation":[{"name":"Federal University of Cear\u00e1 Hospital Complex  Fortaleza Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy Mizue","family":"Kokitsu\u2010Nakata","sequence":"additional","affiliation":[{"name":"Hospital for Rehabilitation of Craniofacial Anomalies, University of S\u00e3o Paulo  Bauru Brazil"},{"name":"Bauru Medical School, University of S\u00e3o Paulo  Bauru Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12098\u2010024\u201005115\u2010z"},{"key":"e_1_2_9_3_1","unstructured":"Clay S. 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