Novel pathogenic variants and quantitative phenotypic analyses of Robinow syndrome : WNT signaling perturbation and phenotypic variability

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MetadadosDescriçãoIdioma
Autor(es): dc.contributorBCM, Department of Molecular and Human Genetics-
Autor(es): dc.contributorBCM, Department of Molecular and Human Genetics-
Autor(es): dc.contributorBMC, Medical Scientist Training Program-
Autor(es): dc.contributorBCM, Department of Molecular and Human Genetics-
Autor(es): dc.contributorTexas Children's Hospital, Houston-
Autor(es): dc.contributorUniversity of Brasilia-
Autor(es): dc.contributorRobinow Syndrome Foundation, Anoka-
Autor(es): dc.contributorBCM, Department of Molecular and Human Genetics-
Autor(es): dc.contributorBCM, Department of Molecular and Human Genetics-
Autor(es): dc.contributorBMC, Medical Scientist Training Program-
Autor(es): dc.contributorBCM, Human Genome Sequencing Center-
Autor(es): dc.contributorGeneDx Inc., Gaithersburg-
Autor(es): dc.contributorUniversity of Brasilia-
Autor(es): dc.contributorUniversity of Brasilia-
Autor(es): dc.contributorBCM, Department of Molecular and Human Genetics-
Autor(es): dc.contributorHuman Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, UTHealth-
Autor(es): dc.contributorBCM, Department of Molecular and Human Genetics-
Autor(es): dc.contributorOxford University Hospitals NHS Foundation Trust, Oxford Centre for Genomic Medicine,-
Autor(es): dc.contributorOxford University Hospitals NHS Foundation Trust, Cardiothoracic Surgery-
Autor(es): dc.contributorNHS Lothian, Edinburgh-
Autor(es): dc.contributorOxford Centre for Genomic Medicine, Oxford University Hospitals NHS Foundation Trust-
Autor(es): dc.contributorOxford University Hospitals NHS Foundation Trust, Pediatric Rheumatology, Nuffield Orthopedic Centre-
Autor(es): dc.contributorBotnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences-
Autor(es): dc.contributorOxford University Hospitals NHS Foundation Trust, Oxford Regional Genetics Laboratories-
Autor(es): dc.contributorOxford University Hospitals NHS Foundation Trust, Oxford Regional Genetics Laboratories-
Autor(es): dc.contributorGreat Ormond Street Hospital NHS Foundation Trust, Radiology Department-
Autor(es): dc.contributorUniversity Clinical Center Zagreb, Department of Pediatric Endocrinology and Diabetes-
Autor(es): dc.contributorThe University of Manchester, School of Biological Sciences, Faculty of Biology, Medicine and Health, Division of Evolution, Infection and Genomics-
Autor(es): dc.contributorManchester University NHS Foundation Trust, St Mary's Hospital, Manchester Center for Genomic Medicine, Health Innovation Manchester-
Autor(es): dc.contributorManchester University NHS Foundation Trust, St Mary's Hospital, Manchester Center for Genomic Medicine, Health Innovation Manchester-
Autor(es): dc.contributorBCM, Human Genome Sequencing Center-
Autor(es): dc.contributorBCM, Department of Molecular and Human Genetics-
Autor(es): dc.contributorTexas Children's Hospital, Houston-
Autor(es): dc.contributorColumbia University, Department of Pediatrics and Medicine-
Autor(es): dc.contributorGeneDx Inc., Gaithersburg-
Autor(es): dc.contributorUniversity of Texas Health Science Center at Houston, McGovern Medical School,Department of Pediatrics-
Autor(es): dc.contributorChildren’s Memorial Hermann Hospital-
Autor(es): dc.contributorUniversity of Texas Health Science Center at Houston, McGovern Medical School,Department of Pediatrics-
Autor(es): dc.contributorChildren’s Memorial Hermann Hospital-
Autor(es): dc.contributorBCM, Department of Molecular and Human Genetics-
Autor(es): dc.contributorGeneDx Inc., Gaithersburg-
Autor(es): dc.contributorArnold Palmer Hospital for Children, Orlando-
Autor(es): dc.contributorDuke University Medical Center, Division of Medical Genetics, Durham-
Autor(es): dc.contributorDuke University Medical Center, Division of Medical Genetics, Durham-
Autor(es): dc.contributorDuke University Medical Center, Division of Medical Genetics, Durham-
Autor(es): dc.contributorInova Fairfax Hospital, Medical Genetics, Falls Church-
Autor(es): dc.contributorCook Children's Hospital, Fort Worth-
Autor(es): dc.contributorUniversity of North Carolina at Chapel Hill School of Medicine, Division of Pediatric Genetics and Metabolism-
Autor(es): dc.contributorState University of Rio de Janeiro-
Autor(es): dc.contributorUniversity of Sao Paulo, Faculdade de Medicina, Instituto da Criança - Hospital das Clinicas HCFMUSP, Unidade de Genética-
Autor(es): dc.contributorMendelics Análise Genômica, São Paulo-
Autor(es): dc.contributorUniversity of Sao Paulo, Ribeirao Preto Medical School, Department of Genetics-
Autor(es): dc.contributorSão Paulo University, Instituto de Tratamento do Câncer Infantil-
Autor(es): dc.contributorHospital Israelita Albert Einstein, Medical School-
Autor(es): dc.contributorQueen Mary University of London, Genomics England and William Harvey Research Institute-
Autor(es): dc.contributorBCM, Human Genome Sequencing Center-
Autor(es): dc.contributorBCM, Department of Molecular and Human Genetics-
Autor(es): dc.contributorBCM, Human Genome Sequencing Center-
Autor(es): dc.contributorBCM, Department of Molecular and Human Genetics-
Autor(es): dc.contributorBCM, Department of Molecular and Human Genetics-
Autor(es): dc.contributorBaylor Genetics, Houston-
Autor(es): dc.contributorBCM, Department of Molecular and Human Genetics-
Autor(es): dc.contributorTexas Children's Hospital, Houston-
Autor(es): dc.contributorBCM, Human Genome Sequencing Center-
Autor(es): dc.contributorBCM, Department of Pediatrics-
Autor(es): dc.contributorBCM, Department of Molecular and Human Genetics-
Autor(es): dc.contributorTexas Children's Hospital, Houston-
Autor(es): dc.contributorBCM, Department of Molecular and Human Genetics-
Autor(es): dc.contributorPacific Northwest Research Institute-
Autor(es): dc.creatorChaofan Zhang-
Autor(es): dc.creatorJolly, Angad-
Autor(es): dc.creatorShayota, Brian J.-
Autor(es): dc.creatorAraújo, Juliana Forte Mazzeu de-
Autor(es): dc.creatorHaowei Du-
Autor(es): dc.creatorDawood, Moez-
Autor(es): dc.creatorSoper, Patricia Celestino-
Autor(es): dc.creatorLima, Ariadne Ramalho de-
Autor(es): dc.creatorFerreira, Bárbara Merfort-
Autor(es): dc.creatorCoban-Akdemir, Zeynep-
Autor(es): dc.creatorWhite, Janson-
Autor(es): dc.creatorShears, Deborah-
Autor(es): dc.creatorThomson, Fraser Robert-
Autor(es): dc.creatorDouglas, Sarah Louise-
Autor(es): dc.creatorWainwright, Andrew-
Autor(es): dc.creatorBailey, Kathryn-
Autor(es): dc.creatorWordsworth, Paul-
Autor(es): dc.creatorOldridge, Mike-
Autor(es): dc.creatorLester, Tracy-
Autor(es): dc.creatorCalder, Alistair D.-
Autor(es): dc.creatorDumic, Katja-
Autor(es): dc.creatorBanka, Siddharth-
Autor(es): dc.creatorDonnai, Dian-
Autor(es): dc.creatorJhangiani, Shalini N.-
Autor(es): dc.creatorPotocki, Lorraine-
Autor(es): dc.creatorChung, Wendy K.-
Autor(es): dc.creatorMora, Sara-
Autor(es): dc.creatorNorthrup, Hope-
Autor(es): dc.creatorAshfaq, Myla-
Autor(es): dc.creatorRosenfeld, Jill A.-
Autor(es): dc.creatorMason, Kati-
Autor(es): dc.creatorPollack, Lynda C.-
Autor(es): dc.creatorMcConkie-Rosell, Allyn-
Autor(es): dc.creatorWei Kelly-
Autor(es): dc.creatorMcDonald, Marie-
Autor(es): dc.creatorHauser, Natalie S.-
Autor(es): dc.creatorLeahy, Peter-
Autor(es): dc.creatorPowell, Cynthia M.-
Autor(es): dc.creatorBoy, Raquel-
Autor(es): dc.creatorHonjo, Rachel Sayuri-
Autor(es): dc.creatorKok, Fernando-
Autor(es): dc.creatorMartelli, Lucia R.-
Autor(es): dc.creatorOdone Filho, Vicente-
Autor(es): dc.creatorGenomics England Research Consortium-
Autor(es): dc.creatorMuzny, Donna M.-
Autor(es): dc.creatorGibbs, Richard A.-
Autor(es): dc.creatorPosey, Jennifer E.-
Autor(es): dc.creatorPengfei Liu-
Autor(es): dc.creatorLupski, James R.-
Autor(es): dc.creatorSutton, V. Reid-
Autor(es): dc.creatorCarvalho, Claudia M. B.-
Data de aceite: dc.date.accessioned2024-10-23T16:19:59Z-
Data de disponibilização: dc.date.available2024-10-23T16:19:59Z-
Data de envio: dc.date.issued2024-10-08-
Data de envio: dc.date.issued2024-10-08-
Data de envio: dc.date.issued2021-
Fonte completa do material: dc.identifierhttp://repositorio.unb.br/handle/10482/50523-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/capes/905711-
Descrição: dc.descriptionRobinow 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.-
Descrição: dc.descriptionFaculdade de Medicina (FM)-
Formato: dc.formatapplication/pdf-
Idioma: dc.languageen-
Publicador: dc.publisherCell Press-
Direitos: dc.rightsAcesso Aberto-
Direitos: dc.rights2021 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/).-
Palavras-chave: dc.subjectRobinow, Síndrome de-
Palavras-chave: dc.subjectDisplasia esquelética-
Palavras-chave: dc.subjectMutação genética-
Título: dc.titleNovel pathogenic variants and quantitative phenotypic analyses of Robinow syndrome : WNT signaling perturbation and phenotypic variability-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional – UNB

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