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dc.contributor.authorChaofan Zhang-
dc.contributor.authorJolly, Angad-
dc.contributor.authorShayota, Brian J.-
dc.contributor.authorAraújo, Juliana Forte Mazzeu de-
dc.contributor.authorHaowei Du-
dc.contributor.authorDawood, Moez-
dc.contributor.authorSoper, Patricia Celestino-
dc.contributor.authorLima, Ariadne Ramalho de-
dc.contributor.authorFerreira, Bárbara Merfort-
dc.contributor.authorCoban-Akdemir, Zeynep-
dc.contributor.authorWhite, Janson-
dc.contributor.authorShears, Deborah-
dc.contributor.authorThomson, Fraser Robert-
dc.contributor.authorDouglas, Sarah Louise-
dc.contributor.authorWainwright, Andrew-
dc.contributor.authorBailey, Kathryn-
dc.contributor.authorWordsworth, Paul-
dc.contributor.authorOldridge, Mike-
dc.contributor.authorLester, Tracy-
dc.contributor.authorCalder, Alistair D.-
dc.contributor.authorDumic, Katja-
dc.contributor.authorBanka, Siddharth-
dc.contributor.authorDonnai, Dian-
dc.contributor.authorJhangiani, Shalini N.-
dc.contributor.authorPotocki, Lorraine-
dc.contributor.authorChung, Wendy K.-
dc.contributor.authorMora, Sara-
dc.contributor.authorNorthrup, Hope-
dc.contributor.authorAshfaq, Myla-
dc.contributor.authorRosenfeld, Jill A.-
dc.contributor.authorMason, Kati-
dc.contributor.authorPollack, Lynda C.-
dc.contributor.authorMcConkie-Rosell, Allyn-
dc.contributor.authorWei Kelly-
dc.contributor.authorMcDonald, Marie-
dc.contributor.authorHauser, Natalie S.-
dc.contributor.authorLeahy, Peter-
dc.contributor.authorPowell, Cynthia M.-
dc.contributor.authorBoy, Raquel-
dc.contributor.authorHonjo, Rachel Sayuri-
dc.contributor.authorKok, Fernando-
dc.contributor.authorMartelli, Lucia R.-
dc.contributor.authorOdone Filho, Vicente-
dc.contributor.authorGenomics England Research Consortium-
dc.contributor.authorMuzny, Donna M.-
dc.contributor.authorGibbs, Richard A.-
dc.contributor.authorPosey, Jennifer E.-
dc.contributor.authorPengfei Liu-
dc.contributor.authorLupski, James R.-
dc.contributor.authorSutton, V. Reid-
dc.contributor.authorCarvalho, Claudia M. B.-
dc.date.accessioned2024-10-08T15:28:25Z-
dc.date.available2024-10-08T15:28:25Z-
dc.date.issued2022-
dc.identifier.citationHuman Genetics and Genomics Advances, [S. l.], n. 3, 100074, 13 jan. 2022.pt_BR
dc.identifier.urihttp://repositorio.unb.br/handle/10482/50523-
dc.language.isoengpt_BR
dc.publisherCell Presspt_BR
dc.rightsAcesso Abertopt_BR
dc.titleNovel pathogenic variants and quantitative phenotypic analyses of Robinow syndrome : WNT signaling perturbation and phenotypic variabilitypt_BR
dc.typeArtigopt_BR
dc.subject.keywordRobinow, Síndrome dept_BR
dc.subject.keywordDisplasia esqueléticapt_BR
dc.subject.keywordMutação genéticapt_BR
dc.rights.license2021 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).pt_BR
dc.description.abstract1Robinow syndrome (RS) is a genetically heterogeneous disorder with six genes that converge on the WNT/planar cell polarity (PCP) signaling pathway implicated (DVL1, DVL3, FZD2, NXN, ROR2, and WNT5A). RS is characterized by skeletal dysplasia and distinctive facial and physical characteristics. To further explore the genetic heterogeneity, paralog contribution, and phenotypic variability of RS, we investigated a cohort of 22 individuals clinically diagnosed with RS from 18 unrelated families. Pathogenic or likely pathogenic var iants in genes associated with RS or RS phenocopies were identified in all 22 individuals, including the first variant to be reported in DVL2. We retrospectively collected medical records of 16 individuals from this cohort and extracted clinical descriptions from 52 pre viously published cases. We performed Human Phenotype Ontology (HPO) based quantitative phenotypic analyses to dissect allele-spe cific phenotypic differences. Individuals with FZD2 variants clustered into two groups with demonstrable phenotypic differences between those with missense and truncating alleles. Probands with biallelic NXN variants clustered together with the majority of pro bands carrying DVL1, DVL2, and DVL3 variants, demonstrating no phenotypic distinction between the NXN-autosomal recessive and dominant forms of RS. While phenotypically similar diseases on the RS differential matched through HPO analysis, clustering using phenotype similarity score placed RS-associated phenotypes in a unique cluster containing WNT5A, FZD2, and ROR2 apart from non-RS-associated paralogs. Through human phenotype analyses of this RS cohort and OMIM clinical synopses of Mendelian disease, this study begins to tease apart specific biologic roles for non-canonical WNT-pathway proteins.pt_BR
dc.contributor.affiliationBCM, Department of Molecular and Human Geneticspt_BR
dc.contributor.affiliationBCM, Department of Molecular and Human Geneticspt_BR
dc.contributor.affiliationBMC, Medical Scientist Training Programpt_BR
dc.contributor.affiliationBCM, Department of Molecular and Human Geneticspt_BR
dc.contributor.affiliationTexas Children's Hospital, Houstonpt_BR
dc.contributor.affiliationUniversity of Brasiliapt_BR
dc.contributor.affiliationRobinow Syndrome Foundation, Anokapt_BR
dc.contributor.affiliationBCM, Department of Molecular and Human Geneticspt_BR
dc.contributor.affiliationBCM, Department of Molecular and Human Geneticspt_BR
dc.contributor.affiliationBMC, Medical Scientist Training Programpt_BR
dc.contributor.affiliationBCM, Human Genome Sequencing Centerpt_BR
dc.contributor.affiliationGeneDx Inc., Gaithersburgpt_BR
dc.contributor.affiliationUniversity of Brasiliapt_BR
dc.contributor.affiliationUniversity of Brasiliapt_BR
dc.contributor.affiliationBCM, Department of Molecular and Human Geneticspt_BR
dc.contributor.affiliationHuman Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, UTHealthpt_BR
dc.contributor.affiliationBCM, Department of Molecular and Human Geneticspt_BR
dc.contributor.affiliationOxford University Hospitals NHS Foundation Trust, Oxford Centre for Genomic Medicine,pt_BR
dc.contributor.affiliationOxford University Hospitals NHS Foundation Trust, Cardiothoracic Surgerypt_BR
dc.contributor.affiliationNHS Lothian, Edinburghpt_BR
dc.contributor.affiliationOxford Centre for Genomic Medicine, Oxford University Hospitals NHS Foundation Trustpt_BR
dc.contributor.affiliationOxford University Hospitals NHS Foundation Trust, Pediatric Rheumatology, Nuffield Orthopedic Centrept_BR
dc.contributor.affiliationBotnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciencespt_BR
dc.contributor.affiliationOxford University Hospitals NHS Foundation Trust, Oxford Regional Genetics Laboratoriespt_BR
dc.contributor.affiliationOxford University Hospitals NHS Foundation Trust, Oxford Regional Genetics Laboratoriespt_BR
dc.contributor.affiliationGreat Ormond Street Hospital NHS Foundation Trust, Radiology Departmentpt_BR
dc.contributor.affiliationUniversity Clinical Center Zagreb, Department of Pediatric Endocrinology and Diabetespt_BR
dc.contributor.affiliationThe University of Manchester, School of Biological Sciences, Faculty of Biology, Medicine and Health, Division of Evolution, Infection and Genomicspt_BR
dc.contributor.affiliationManchester University NHS Foundation Trust, St Mary's Hospital, Manchester Center for Genomic Medicine, Health Innovation Manchesterpt_BR
dc.contributor.affiliationManchester University NHS Foundation Trust, St Mary's Hospital, Manchester Center for Genomic Medicine, Health Innovation Manchesterpt_BR
dc.contributor.affiliationBCM, Human Genome Sequencing Centerpt_BR
dc.contributor.affiliationBCM, Department of Molecular and Human Geneticspt_BR
dc.contributor.affiliationTexas Children's Hospital, Houstonpt_BR
dc.contributor.affiliationColumbia University, Department of Pediatrics and Medicinept_BR
dc.contributor.affiliationGeneDx Inc., Gaithersburgpt_BR
dc.contributor.affiliationUniversity of Texas Health Science Center at Houston, McGovern Medical School,Department of Pediatricspt_BR
dc.contributor.affiliationChildren’s Memorial Hermann Hospitalpt_BR
dc.contributor.affiliationUniversity of Texas Health Science Center at Houston, McGovern Medical School,Department of Pediatricspt_BR
dc.contributor.affiliationChildren’s Memorial Hermann Hospitalpt_BR
dc.contributor.affiliationBCM, Department of Molecular and Human Geneticspt_BR
dc.contributor.affiliationGeneDx Inc., Gaithersburgpt_BR
dc.contributor.affiliationArnold Palmer Hospital for Children, Orlandopt_BR
dc.contributor.affiliationDuke University Medical Center, Division of Medical Genetics, Durhampt_BR
dc.contributor.affiliationDuke University Medical Center, Division of Medical Genetics, Durhampt_BR
dc.contributor.affiliationDuke University Medical Center, Division of Medical Genetics, Durhampt_BR
dc.contributor.affiliationInova Fairfax Hospital, Medical Genetics, Falls Churchpt_BR
dc.contributor.affiliationCook Children's Hospital, Fort Worthpt_BR
dc.contributor.affiliationUniversity of North Carolina at Chapel Hill School of Medicine, Division of Pediatric Genetics and Metabolismpt_BR
dc.contributor.affiliationState University of Rio de Janeiropt_BR
dc.contributor.affiliationUniversity of Sao Paulo, Faculdade de Medicina, Instituto da Criança - Hospital das Clinicas HCFMUSP, Unidade de Genéticapt_BR
dc.contributor.affiliationMendelics Análise Genômica, São Paulopt_BR
dc.contributor.affiliationUniversity of Sao Paulo, Ribeirao Preto Medical School, Department of Geneticspt_BR
dc.contributor.affiliationSão Paulo University, Instituto de Tratamento do Câncer Infantilpt_BR
dc.contributor.affiliationHospital Israelita Albert Einstein, Medical Schoolpt_BR
dc.contributor.affiliationQueen Mary University of London, Genomics England and William Harvey Research Institutept_BR
dc.contributor.affiliationBCM, Human Genome Sequencing Centerpt_BR
dc.contributor.affiliationBCM, Department of Molecular and Human Geneticspt_BR
dc.contributor.affiliationBCM, Human Genome Sequencing Centerpt_BR
dc.contributor.affiliationBCM, Department of Molecular and Human Geneticspt_BR
dc.contributor.affiliationBCM, Department of Molecular and Human Geneticspt_BR
dc.contributor.affiliationBaylor Genetics, Houstonpt_BR
dc.contributor.affiliationBCM, Department of Molecular and Human Geneticspt_BR
dc.contributor.affiliationTexas Children's Hospital, Houstonpt_BR
dc.contributor.affiliationBCM, Human Genome Sequencing Centerpt_BR
dc.contributor.affiliationBCM, Department of Pediatricspt_BR
dc.contributor.affiliationBCM, Department of Molecular and Human Geneticspt_BR
dc.contributor.affiliationTexas Children's Hospital, Houstonpt_BR
dc.contributor.affiliationBCM, Department of Molecular and Human Geneticspt_BR
dc.contributor.affiliationPacific Northwest Research Institutept_BR
dc.description.unidadeFaculdade de Medicina (FM)pt_BR
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