Novel mutations in PIEZO1 cause an autosomal recessive generalized lymphatic dysplasia with non-immune hydrops fetalis

  • Nat Commun. 2015 Sep 3;6:8085. doi: 10.1038/ncomms9085.
Elisavet Fotiou  1 ,  Silvia Martin-Almedina  1 ,  Michael A Simpson  2 ,  Shin Lin  3  4 ,  Kristiana Gordon  5 ,  Glen Brice  6 ,  Giles Atton  6 ,  Iona Jeffery  7 ,  David C Rees  8 ,  Cyril Mignot  9 ,  Julie Vogt  10 ,  Tessa Homfray  6 ,  Michael P Snyder  4 ,  Stanley G Rockson  3 ,  Steve Jeffery  1 ,  Peter S Mortimer  1 ,  Sahar Mansour  6 ,  Pia Ostergaard  1
Affiliations
  • 1. Cardiovascular and Cell Sciences Institute, St. George's University of London, Cranmer Terrace, London SW17 0RE, UK.
  • 2. Department of Medical and Molecular Genetics, Division of Genetics and Molecular Medicine, Kings College London School of Medicine, Guy's Hospital, London SE1 9RY, UK.
  • 3. Division of Cardiovascular Medicine, Stanford University, Stanford, California 94305, USA.
  • 4. Department of Genetics, Stanford University, Stanford, California 94305, USA.
  • 5. Department of Dermatology, St. George's Healthcare NHS Trust, London SW17 0QT, UK.
  • 6. South West Thames Regional Genetics Unit, St. George's University of London, London SW17 0RE, UK.
  • 7. Pathology Department, St. George's University of London, London SW17 0RE, UK.
  • 8. Department of Haematological Medicine, King's College London School of Medicine, King's College Hospital, London SE5 9RS, UK.
  • 9. Département de Génétique, APHP, GH Pitié-Salpêtrière, Centre de Référence des Déficiences Intellectuelles de Causes Rares, 75013 Paris, France.
  • 10. West Midlands Regional Genetics Service, Clinical Genetics Unit, Birmingham Women's Hospital, Birmingham B15 2TG, UK.
PMID: 26333996 DOI: 10.1038/ncomms9085
Abstract

Generalized lymphatic dysplasia (GLD) is a rare form of primary lymphoedema characterized by a uniform, widespread lymphoedema affecting all segments of the body, with systemic involvement such as intestinal and/or pulmonary lymphangiectasia, pleural effusions, chylothoraces and/or pericardial effusions. This may present prenatally as non-immune hydrops. Here we report homozygous and compound heterozygous mutations in PIEZO1, resulting in an autosomal recessive form of GLD with a high incidence of non-immune hydrops fetalis and childhood onset of facial and four limb lymphoedema. Mutations in PIEZO1, which encodes a mechanically activated ion channel, have been reported with autosomal dominant dehydrated hereditary stomatocytosis and non-immune hydrops of unknown aetiology. Besides its role in red blood cells, our findings indicate that PIEZO1 is also involved in the development of lymphatic structures.