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.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anemia, Hemolytic, Congenital / genetics*
  • Blotting, Western
  • Child
  • Child, Preschool
  • Craniofacial Abnormalities / diagnostic imaging
  • Craniofacial Abnormalities / genetics*
  • Female
  • Heterozygote
  • Humans
  • Hydrops Fetalis / genetics*
  • Infant, Newborn
  • Ion Channels / genetics*
  • Lymphangiectasis, Intestinal / diagnostic imaging
  • Lymphangiectasis, Intestinal / genetics*
  • Lymphedema / diagnostic imaging
  • Lymphedema / genetics*
  • Lymphoscintigraphy
  • Male
  • Mutation
  • Sequence Analysis, DNA


  • Ion Channels
  • PIEZO1 protein, human

Supplementary concepts

  • Hennekam lymphangiectasia lymphedema syndrome
  • Xerocytosis, hereditary