Novel mutations in PIEZO1 cause an autosomal recessive generalized lymphatic dysplasia with non-immune hydrops fetalis.
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.
Cardiovascular and Cell Sciences Institute, St. George's University of London, Cranmer Terrace, London SW17 0RE, UK.
Elisavet
E
Fotiou
Cardiovascular and Cell Sciences Institute, St. George's University of London, Cranmer Terrace, London SW17 0RE, UK.
Silvia
S
Martin-Almedina
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.
Michael A
MA
Simpson
Division of Cardiovascular Medicine, Stanford University, Stanford, California 94305, USA.|Department of Genetics, Stanford University, Stanford, California 94305, USA.
Shin
S
Lin
Department of Dermatology, St. George's Healthcare NHS Trust, London SW17 0QT, UK.
Kristiana
K
Gordon
South West Thames Regional Genetics Unit, St. George's University of London, London SW17 0RE, UK.
Glen
G
Brice
South West Thames Regional Genetics Unit, St. George's University of London, London SW17 0RE, UK.
Giles
G
Atton
Pathology Department, St. George's University of London, London SW17 0RE, UK.
Iona
I
Jeffery
Department of Haematological Medicine, King's College London School of Medicine, King's College Hospital, London SE5 9RS, UK.
David C
DC
Rees
Département de Génétique, APHP, GH Pitié-Salpêtrière, Centre de Référence des Déficiences Intellectuelles de Causes Rares, 75013 Paris, France.
Cyril
C
Mignot
West Midlands Regional Genetics Service, Clinical Genetics Unit, Birmingham Women's Hospital, Birmingham B15 2TG, UK.
Julie
J
Vogt
South West Thames Regional Genetics Unit, St. George's University of London, London SW17 0RE, UK.
Tessa
T
Homfray
Department of Genetics, Stanford University, Stanford, California 94305, USA.
Michael P
MP
Snyder
Division of Cardiovascular Medicine, Stanford University, Stanford, California 94305, USA.
Stanley G
SG
Rockson
Cardiovascular and Cell Sciences Institute, St. George's University of London, Cranmer Terrace, London SW17 0RE, UK.
Steve
S
Jeffery
Cardiovascular and Cell Sciences Institute, St. George's University of London, Cranmer Terrace, London SW17 0RE, UK.
Peter S
PS
Mortimer
South West Thames Regional Genetics Unit, St. George's University of London, London SW17 0RE, UK.
Sahar
S
Mansour
Cardiovascular and Cell Sciences Institute, St. George's University of London, Cranmer Terrace, London SW17 0RE, UK.
Pia
http://orcid.org/0000-0002-2190-1356
P
Ostergaard
D000293:Adolescent; D000328:Adult; D000745:Anemia, Hemolytic, Congenital / Q000235:genetics*; D015153:Blotting, Western; D002648:Child; D002675:Child, Preschool; D019465:Craniofacial Abnormalities / Q000000981:diagnostic imaging / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006801:Humans; D015160:Hydrops Fetalis / Q000235:genetics*; D007231:Infant, Newborn; D007473:Ion Channels / Q000235:genetics*; D008201:Lymphangiectasis, Intestinal / Q000000981:diagnostic imaging / Q000235:genetics*; D008209:Lymphedema / Q000000981:diagnostic imaging / Q000235:genetics*; D061305:Lymphoscintigraphy; D008297:Male; D009154:Mutation; D017422:Sequence Analysis, DNA
D007473:Ion Channels; C515204:PIEZO1 protein, human