Novel mutations in PIEZO1 cause an autosomal recessive generalized lymphatic dysplasia with non-immune hydrops fetalis.
Novel mutations in PIEZO1 cause an autosomal recessive generalized lymphatic dysplasia with non-immune hydrops fetalis.
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DOI：
10.1038/ncomms9085
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发表时间：
2015-09-03
影响因子：
16.6
通讯作者：
Ostergaard P
中科院分区：
文献类型：
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作者：
Fotiou E;Martin-Almedina S;Simpson MA;Lin S;Gordon K;Brice G;Atton G;Jeffery I;Rees DC;Mignot C;Vogt J;Homfray T;Snyder MP;Rockson SG;Jeffery S;Mortimer PS;Mansour S;Ostergaard P
全身性淋巴管发育不良（GLD）是一种罕见的原发性淋巴水肿，其特征是影响身体所有部位的均匀、广泛的淋巴水肿，并伴有全身性受累，例如肠和/或肺淋巴管扩张、胸腔积液、乳糜胸和/或心包积液。这可能在产前表现为非免疫性水肿。在这里，我们报告了 PIEZO1 的纯合和复合杂合突变，导致常染色体隐性遗传形式的 GLD，非免疫性胎儿水肿以及儿童期发病的面部和四肢淋巴水肿的发生率很高。据报道，编码机械激活离子通道的 PIEZO1 突变与常染色体显性脱水遗传性口红细胞增多症和病因不明的非免疫性水肿有关。除了在红细胞中的作用外，我们的研究结果表明 PIEZO1 还参与淋巴结构的发育。原发性淋巴水肿可导致四肢肿胀和面部畸形。在这里，作者提出的证据表明，PIEZO1 的复合杂合和纯合突变会导致常染色体隐性遗传形式的全身性淋巴管发育不良。
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. Primary lymphoedema can lead to the swelling of the extremities and facial dysmorphism. Here the authors present evidence that compound heterozygous and homozygous mutations in PIEZO1 result in an autosomal recessive form of generalised lymphatic dysplasia.