Impaired PIEZO1 function in patients with a novel autosomal recessive congenital lymphatic dysplasia

Viktor Lukacs, Jayanti Mathur, Rong Mao, Pinar Bayrak-Toydemir, Melinda Procter, Stuart M. Cahalan, Helen J. Kim, Michael Bandell, Nicola Longo, Ronald W. Day, David A. Stevenson, Ardem Patapoutian () and Bryan L. Krock ()
Additional contact information
Viktor Lukacs: Howard Hughes Medical Institute, Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute
Jayanti Mathur: Genomics Institute of the Novartis Research Foundation
Rong Mao: ARUP Institute for Clinical and Experimental Pathology, ARUP Laboratories
Pinar Bayrak-Toydemir: ARUP Institute for Clinical and Experimental Pathology, ARUP Laboratories
Melinda Procter: ARUP Institute for Clinical and Experimental Pathology, ARUP Laboratories
Stuart M. Cahalan: Howard Hughes Medical Institute, Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute
Helen J. Kim: Integrative Structural and Computational Biology, The Scripps Research Institute
Michael Bandell: Genomics Institute of the Novartis Research Foundation
Nicola Longo: University of Utah
Ronald W. Day: University of Utah
David A. Stevenson: University of Utah
Ardem Patapoutian: Howard Hughes Medical Institute, Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute
Bryan L. Krock: ARUP Institute for Clinical and Experimental Pathology, ARUP Laboratories

Nature Communications, 2015, vol. 6, issue 1, 1-7

Abstract: Abstract Piezo1 ion channels are mediators of mechanotransduction in several cell types including the vascular endothelium, renal tubular cells and erythrocytes. Gain-of-function mutations in PIEZO1 cause an autosomal dominant haemolytic anaemia in humans called dehydrated hereditary stomatocytosis. However, the phenotypic consequence of PIEZO1 loss of function in humans has not previously been documented. Here we discover a novel role of this channel in the lymphatic system. Through whole-exome sequencing, we identify biallelic mutations in PIEZO1 (a splicing variant leading to early truncation and a non-synonymous missense variant) in a pair of siblings affected with persistent lymphoedema caused by congenital lymphatic dysplasia. Analysis of patients’ erythrocytes as well as studies in a heterologous system reveal greatly attenuated PIEZO1 function in affected alleles. Our results delineate a novel clinical category of PIEZO1-associated hereditary lymphoedema.

Date: 2015
References: Add references at CitEc
Citations: View citations in EconPapers (6)

Downloads: (external link)
https://www.nature.com/articles/ncomms9329 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9329

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms9329

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().