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

• DOI: 10.1038/ncomms9329
• Publication Date: 2015-09-21T10:57:52Z
• Authors: Viktor Lukacs; Jayanti Mathur; Rong Mao; Pinar Bayrak-Toyd...; Melinda Procter; Stuart M. Cahalan; Helen J. Kim; Michael Bandell; Nicola Longo; Ronald W. Day; David A. Stevenson; Ardem Patapoutian; Bryan L. Krock
• Keywords: Piezo1; Lymphatic Endothelium; Loss function; Penetrance

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 PIEZO1 cause an autosomal dominant haemolytic anaemia humans called dehydrated hereditary stomatocytosis. However, phenotypic consequence loss function has not previously been documented. Here we discover a novel role this channel lymphatic system. Through whole-exome sequencing, identify biallelic (a splicing variant leading to early truncation non-synonymous missense variant) pair siblings affected with persistent lymphoedema caused by congenital dysplasia. Analysis patients’ erythrocytes as well studies heterologous system reveal greatly attenuated alleles. Our results delineate clinical category PIEZO1-associated lymphoedema.