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

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.

• Authors: Elisavet Fotiou, Silvia Martin-Almedina, Michael A Simpson, Shin Lin, Kristiana Gordon, Glen Brice, Giles Atton, Iona Jeffery, David C Rees, Cyril Mignot, Julie Vogt, Tessa Homfray, Michael P Snyder, Stanley G Rockson, Steve Jeffery, Peter S Mortimer, Sahar Mansour, Pia Ostergaard
• Journal: Nature communications (Nat Commun) Vol. 6 Pg. 8085 (Sep 03 2015) ISSN: 2041-1723 [Electronic] England
• PMID: 26333996 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Ion Channels
• PIEZO1 protein, human

Topics

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