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Research Article

Loss-of-Function Mutations in PTPN11 Cause Metachondromatosis, but Not Ollier Disease or Maffucci Syndrome

  • Margot E. Bowen equal contributor,

    equal contributor Contributed equally to this work with: Margot E. Bowen, Eric D. Boyden

    Affiliations: Department of Orthopaedic Surgery, Children's Hospital Boston and Harvard Medical School, Boston, Massachusetts, United States of America, Howard Hughes Medical Institute, Boston, Massachusetts, United States of America, Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America

    X
  • Eric D. Boyden equal contributor,

    equal contributor Contributed equally to this work with: Margot E. Bowen, Eric D. Boyden

    Affiliations: Department of Orthopaedic Surgery, Children's Hospital Boston and Harvard Medical School, Boston, Massachusetts, United States of America, Howard Hughes Medical Institute, Boston, Massachusetts, United States of America, Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America

    X
  • Ingrid A. Holm,

    Affiliations: Division of Genetics, Program in Genomics, and The Manton Center for Orphan Disease Research, Children's Hospital Boston, Boston, Massachusetts, United States of America, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, United States of America

    X
  • Belinda Campos-Xavier,

    Affiliation: Division of Molecular Pediatrics, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland

    X
  • Luisa Bonafé,

    Affiliation: Division of Molecular Pediatrics, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland

    X
  • Andrea Superti-Furga,

    Affiliation: Division of Molecular Pediatrics, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland

    X
  • Shiro Ikegawa,

    Affiliation: Laboratory for Bone and Joint Diseases, Center for Genomic Medicine, RIKEN, Tokyo, Japan

    X
  • Valerie Cormier-Daire,

    Affiliation: Department of Medical Genetics, Paris Descartes University, INSERM U781, Hôpital Necker Enfants Malades, Paris, France

    X
  • Judith V. Bovée,

    Affiliation: Department of Pathology, Leiden University Medical Centre, Leiden, The Netherlands

    X
  • Twinkal C. Pansuriya,

    Affiliation: Department of Pathology, Leiden University Medical Centre, Leiden, The Netherlands

    X
  • Sérgio B. de Sousa,

    Affiliation: Department of Medical Genetics, Hospital Pediátrico de Coimbra, Coimbra, Portugal

    X
  • Ravi Savarirayan,

    Affiliations: Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, Melbourne, Australia, Department of Pediatrics, University of Melbourne, Melbourne, Australia

    X
  • Elena Andreucci,

    Affiliations: Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, Melbourne, Australia, Department of Pediatrics, University of Melbourne, Melbourne, Australia, Department of Clinical Pathophysiology, University of Florence and Meyer Children's Hospital Genetics Unit, Florence, Italy

    X
  • Miikka Vikkula,

    Affiliation: de Duve Institute, Université Catholique de Louvain, Brussels, Belgium

    X
  • Livia Garavelli,

    Affiliation: Department of Clinical Genetics, Arcispedale S. Maria Nuova, Reggio Emilia, Italy

    X
  • Caroline Pottinger,

    Affiliation: Merseyside and Chesire Regional Genetics Service, Alder Hey Hospital, Liverpool, United Kingdom

    X
  • Toshihiko Ogino,

    Affiliation: Department of Orthopaedic Surgery, Yamagata University Faculty of Medicine, Yamagata, Japan

    X
  • Akinori Sakai,

    Affiliation: Department of Orthopaedic Surgery, University of Occupational and Environmental Health, Kitakyushu, Japan

    X
  • Bianca M. Regazzoni,

    Affiliation: Department of Pediatrics, S. Anna Hospital, Lugano, Switzerland

    X
  • Wim Wuyts,

    Affiliation: Department of Medical Genetics, University of Antwerp, Antwerp, Belgium

    X
  • Luca Sangiorgi,

    Affiliation: Department of Medical Genetics, Rizzoli Orthopaedic Institute, Bologna, Italy

    X
  • Elena Pedrini,

    Affiliation: Department of Medical Genetics, Rizzoli Orthopaedic Institute, Bologna, Italy

    X
  • Mei Zhu,

    Affiliations: Howard Hughes Medical Institute, Boston, Massachusetts, United States of America, Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America

    X
  • Harry P. Kozakewich,

    Affiliation: Department of Pathology, Children's Hospital Boston and Harvard Medical School, Boston, Massachusetts, United States of America

    X
  • James R. Kasser,

    Affiliation: Department of Orthopaedic Surgery, Children's Hospital Boston and Harvard Medical School, Boston, Massachusetts, United States of America

    X
  • Jon G. Seidman,

    Affiliations: Howard Hughes Medical Institute, Boston, Massachusetts, United States of America, Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America

    X
  • Kyle C. Kurek mail,

    kyle.kurek@childrens.harvard.edu

    Affiliations: Department of Orthopaedic Surgery, Children's Hospital Boston and Harvard Medical School, Boston, Massachusetts, United States of America, Department of Pathology, Children's Hospital Boston and Harvard Medical School, Boston, Massachusetts, United States of America

    X
  • Matthew L. Warman

    Affiliations: Department of Orthopaedic Surgery, Children's Hospital Boston and Harvard Medical School, Boston, Massachusetts, United States of America, Howard Hughes Medical Institute, Boston, Massachusetts, United States of America, Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America

    X
  • Published: April 14, 2011
  • DOI: 10.1371/journal.pgen.1002050

About the Authors

Margot E. Bowen, Eric D. Boyden, James R. Kasser, Kyle C. Kurek, Matthew L. Warman
Department of Orthopaedic Surgery, Children's Hospital Boston and Harvard Medical School, Boston, Massachusetts, United States of America
Margot E. Bowen, Eric D. Boyden, Mei Zhu, Jon G. Seidman, Matthew L. Warman
Howard Hughes Medical Institute, Boston, Massachusetts, United States of America
Margot E. Bowen, Eric D. Boyden, Mei Zhu, Jon G. Seidman, Matthew L. Warman
Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America
Ingrid A. Holm
Division of Genetics, Program in Genomics, and The Manton Center for Orphan Disease Research, Children's Hospital Boston, Boston, Massachusetts, United States of America
Ingrid A. Holm
Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, United States of America
Belinda Campos-Xavier, Luisa Bonafé, Andrea Superti-Furga
Division of Molecular Pediatrics, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
Shiro Ikegawa
Laboratory for Bone and Joint Diseases, Center for Genomic Medicine, RIKEN, Tokyo, Japan
Valerie Cormier-Daire
Department of Medical Genetics, Paris Descartes University, INSERM U781, Hôpital Necker Enfants Malades, Paris, France
Judith V. Bovée, Twinkal C. Pansuriya
Department of Pathology, Leiden University Medical Centre, Leiden, The Netherlands
Sérgio B. de Sousa
Department of Medical Genetics, Hospital Pediátrico de Coimbra, Coimbra, Portugal
Ravi Savarirayan, Elena Andreucci
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, Melbourne, Australia
Ravi Savarirayan, Elena Andreucci
Department of Pediatrics, University of Melbourne, Melbourne, Australia
Elena Andreucci
Department of Clinical Pathophysiology, University of Florence and Meyer Children's Hospital Genetics Unit, Florence, Italy
Miikka Vikkula
de Duve Institute, Université Catholique de Louvain, Brussels, Belgium
Livia Garavelli
Department of Clinical Genetics, Arcispedale S. Maria Nuova, Reggio Emilia, Italy
Caroline Pottinger
Merseyside and Chesire Regional Genetics Service, Alder Hey Hospital, Liverpool, United Kingdom
Toshihiko Ogino
Department of Orthopaedic Surgery, Yamagata University Faculty of Medicine, Yamagata, Japan
Akinori Sakai
Department of Orthopaedic Surgery, University of Occupational and Environmental Health, Kitakyushu, Japan
Bianca M. Regazzoni
Department of Pediatrics, S. Anna Hospital, Lugano, Switzerland
Wim Wuyts
Department of Medical Genetics, University of Antwerp, Antwerp, Belgium
Luca Sangiorgi, Elena Pedrini
Department of Medical Genetics, Rizzoli Orthopaedic Institute, Bologna, Italy
Harry P. Kozakewich, Kyle C. Kurek
Department of Pathology, Children's Hospital Boston and Harvard Medical School, Boston, Massachusetts, United States of America

Corresponding Author

Email: kyle.kurek@childrens.harvard.edu

Competing Interests

The authors have declared that no competing interests exist.

Author Contributions

Conceived and designed the experiments: MEB EDB MZ JGS KCK MLW. Performed the experiments: MEB EDB KCK. Analyzed the data: MEB EDB HPK JGS KCK MLW. Contributed reagents/materials/analysis tools: IAH BC-X LB AS-F SI VC-D JVB TCP SBdS RS EA MV LG CP TO AS BMR WW LS EP MZ HPK JRK JGS. Wrote the paper: MEB EDB KCK MLW.