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Cohesin complex-associated holoprosencephaly.
Kruszka, Paul; Berger, Seth I; Casa, Valentina; Dekker, Mike R; Gaesser, Jenna; Weiss, Karin; Martinez, Ariel F; Murdock, David R; Louie, Raymond J; Prijoles, Eloise J; Lichty, Angie W; Brouwer, Oebele F; Zonneveld-Huijssoon, Evelien; Stephan, Mark J; Hogue, Jacob; Hu, Ping; Tanima-Nagai, Momoko; Everson, Joshua L; Prasad, Chitra; Cereda, Anna; Iascone, Maria; Schreiber, Allison; Zurcher, Vickie; Corsten-Janssen, Nicole; Escobar, Luis; Clegg, Nancy J; Delgado, Mauricio R; Hajirnis, Omkar; Balasubramanian, Meena; Kayserili, Hülya; Deardorff, Matthew; Poot, Raymond A; Wendt, Kerstin S; Lipinski, Robert J; Muenke, Maximilian.
Afiliação
  • Kruszka P; Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
  • Berger SI; Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
  • Casa V; Department of Cell Biology, Erasmus MC, Rotterdam, The Netherlands.
  • Dekker MR; Department of Cell Biology, Erasmus MC, Rotterdam, The Netherlands.
  • Gaesser J; Department of Pediatrics, Division of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.
  • Weiss K; Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
  • Martinez AF; Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
  • Murdock DR; Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
  • Louie RJ; Greenwood Genetic Center, JC Self Research Institute of Human Genetics, Greenwood, SC, USA.
  • Prijoles EJ; Greenwood Genetic Center, JC Self Research Institute of Human Genetics, Greenwood, SC, USA.
  • Lichty AW; Greenwood Genetic Center, JC Self Research Institute of Human Genetics, Greenwood, SC, USA.
  • Brouwer OF; Department of Neurology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • Zonneveld-Huijssoon E; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • Stephan MJ; Department of Pediatrics, University of Washington, Seattle, WA, USA.
  • Hogue J; Division of Clinical Genetics, Department of Pediatrics, Madigan Army Hospital, Tacoma, WA, USA.
  • Hu P; Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
  • Tanima-Nagai M; Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
  • Everson JL; Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA.
  • Prasad C; Molecular and Environmental Toxicology Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
  • Cereda A; Children's Health Research Institute, London, ON, Canada.
  • Iascone M; Department of Pediatrics, ASST Papa Giovanni XXIII, Bergamo, Italy.
  • Schreiber A; Laboratorio di Genetica Medica, ASST Papa Giovanni XXIII, Bergamo, Italy.
  • Zurcher V; Genomic Medicine Institute, Cleveland Clinic, Cleveland, OH, USA.
  • Corsten-Janssen N; Genomic Medicine Institute, Cleveland Clinic, Cleveland, OH, USA.
  • Escobar L; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • Clegg NJ; Peyton Manning Children's Hospital at St. Vincent, Medical Genetics and Neurodevelopment Center, Indianapolis, IN, USA.
  • Delgado MR; Texas Scottish Rite Hospital for Children, Dallas, TX, USA.
  • Hajirnis O; Texas Scottish Rite Hospital for Children, Dallas, TX, USA.
  • Balasubramanian M; Department of Neurology and Neurotherapeutics UT Southwestern Medical Center Dallas, TX, USA.
  • Kayserili H; Pediatric Neurology, Synapses Child Neurology and Development Centre, Thane, Maharashtra, India.
  • Deardorff M; Sheffield Clinical Genetics Service, Sheffield Children's, NHS Foundation Trust, Sheffield, UK.
  • Poot RA; Academic Unit of Child Health, University of Sheffield, Sheffield, UK.
  • Wendt KS; Medical Genetics, Medical Faculty, Koç University, Istanbul, Turkey.
  • Lipinski RJ; The Division of Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Muenke M; The Department of Pediatrics, The Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA, USA.
Brain ; 142(9): 2631-2643, 2019 09 01.
Article em En | MEDLINE | ID: mdl-31334757
Marked by incomplete division of the embryonic forebrain, holoprosencephaly is one of the most common human developmental disorders. Despite decades of phenotype-driven research, 80-90% of aneuploidy-negative holoprosencephaly individuals with a probable genetic aetiology do not have a genetic diagnosis. Here we report holoprosencephaly associated with variants in the two X-linked cohesin complex genes, STAG2 and SMC1A, with loss-of-function variants in 10 individuals and a missense variant in one. Additionally, we report four individuals with variants in the cohesin complex genes that are not X-linked, SMC3 and RAD21. Using whole mount in situ hybridization, we show that STAG2 and SMC1A are expressed in the prosencephalic neural folds during primary neurulation in the mouse, consistent with forebrain morphogenesis and holoprosencephaly pathogenesis. Finally, we found that shRNA knockdown of STAG2 and SMC1A causes aberrant expression of HPE-associated genes ZIC2, GLI2, SMAD3 and FGFR1 in human neural stem cells. These findings show the cohesin complex as an important regulator of median forebrain development and X-linked inheritance patterns in holoprosencephaly.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Cromossômicas não Histona / Holoprosencefalia / Proteínas de Ciclo Celular Tipo de estudo: Risk_factors_studies Limite: Adolescent / Animals / Child / Child, preschool / Female / Humans / Infant / Male / Newborn Idioma: En Ano de publicação: 2019 Tipo de documento: Article
Texto completo
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PubMed Links
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Cromossômicas não Histona / Holoprosencefalia / Proteínas de Ciclo Celular Tipo de estudo: Risk_factors_studies Limite: Adolescent / Animals / Child / Child, preschool / Female / Humans / Infant / Male / Newborn Idioma: En Ano de publicação: 2019 Tipo de documento: Article