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Gain-of-function mutations in\n                    <jats:italic>PIEZO1<\/jats:italic>\n                    cause an autosomal dominant haemolytic anaemia in humans called dehydrated hereditary stomatocytosis. However, the phenotypic consequence of\n                    <jats:italic>PIEZO1<\/jats:italic>\n                    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\n                    <jats:italic>PIEZO1<\/jats:italic>\n                    (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\u2019 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.\n                  <\/jats:p>","DOI":"10.1038\/ncomms9329","type":"journal-article","created":{"date-parts":[[2015,9,21]],"date-time":"2015-09-21T06:57:52Z","timestamp":1442818672000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":297,"title":["Impaired PIEZO1 function in patients with a novel autosomal recessive congenital lymphatic dysplasia"],"prefix":"10.1038","volume":"6","author":[{"given":"Viktor","family":"Lukacs","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayanti","family":"Mathur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pinar","family":"Bayrak-Toydemir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melinda","family":"Procter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart M.","family":"Cahalan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0096-7740","authenticated-orcid":false,"given":"Helen J.","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Bandell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Longo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald W.","family":"Day","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Stevenson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ardem","family":"Patapoutian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan L.","family":"Krock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,9,21]]},"reference":[{"key":"BFncomms9329_CR1","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1038\/emboj.2011.456","volume":"31","author":"L Planas-Paz","year":"2012","unstructured":"Planas-Paz, L. et al. Mechanoinduction of lymph vessel expansion. EMBO J. 31, 788\u2013804 (2012).","journal-title":"EMBO J."},{"key":"BFncomms9329_CR2","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1016\/j.devcel.2011.12.020","volume":"22","author":"A Sabine","year":"2012","unstructured":"Sabine, A. et al. Mechanotransduction, PROX1, and FOXC2 cooperate to control connexin37 and calcineurin during lymphatic-valve formation. Dev. Cell 22, 430\u2013445 (2012).","journal-title":"Dev. Cell"},{"key":"BFncomms9329_CR3","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1126\/science.1193270","volume":"330","author":"B Coste","year":"2010","unstructured":"Coste, B. et al. Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. 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Piezo1-dependent stretch-activated channels are inhibited by Polycystin-2 in renal tubular epithelial cells. EMBO Rep. 14, 1143\u20131148 (2013).","journal-title":"EMBO Rep."},{"key":"BFncomms9329_CR10","doi-asserted-by":"publisher","first-page":"70","DOI":"10.3324\/haematol.2013.086090","volume":"99","author":"A Faucherre","year":"2014","unstructured":"Faucherre, A., Kissa, K., Nargeot, J., Mangoni, M. E. & Jopling, C. Piezo1 plays a role in erythrocyte volume homeostasis. Haematologica 99, 70\u201375 (2014).","journal-title":"Haematologica"},{"key":"BFncomms9329_CR11","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.tcb.2014.10.003","volume":"25","author":"SH Woo","year":"2015","unstructured":"Woo, S. H., Lumpkin, E. A. & Patapoutian, A. Merkel cells and neurons keep in touch. 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