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

Lukacs, Viktor and Mathur, Jayanti and Bayrak-Toydemir, Pinar and Rong, Mao and Longo, Nicola and Day, Ronald and Procter, Melinda and Cahalan, Stuart and Kim, Helen J and Bandell, Michael and Stevenson, David A and Patapoutian, Ardem and Krock, Bryan L (2015) Impaired PIEZO1 function in patients with a novel autosomal recessive congenital lymphatic dysplasia. Nature communications, 6. p. 8329. ISSN 2041-1723

Abstract

Piezo1 ion channels are mediators of mechanotransduction in a growing number of cell types including the vascular endothelium, renal tubular cells and erythrocytes. Gain-of-function mutations in PIEZO1 cause an autosomal dominant hemolytic anemia in humans called dehydrated hereditary stomatocytosis. However, the phenotypic consequence of PIEZO1 loss of function in humans has not previously been documented. Here we describe a novel role of this channel in the lymphatic system. Through whole exome sequencing, we have identified biallelic mutations in PIEZO1 in a pair of siblings affected with congenital lymphatic dysplasia. Ex vivo analysis of the patient’s cells as well as in vitro studies in a heterologous system revealed greatly attenuated PIEZO1 function in the patients. Our results delineate a novel clinical category of PIEZO1-associated hereditary lymphedema.

Item Type: Article
Date Deposited: 26 Apr 2016 23:45
Last Modified: 26 Apr 2016 23:45
URI: https://oak.novartis.com/id/eprint/26176

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