AUTHOR=Han Shuai , Guo Xin , Wang Xiaogang , Lin Huijun , Yu Yiqi , Shu Jing , Dong Minyue , Yang Liwei 

TITLE=A Novel Homozygous Missense Mutation of PIEZO1 Leading to Lymphatic Malformation-6 Identified in a Family With Three Adverse Pregnancy Outcomes due to Nonimmune Fetal Hydrops

JOURNAL=Frontiers in Genetics

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.856046

DOI=10.3389/fgene.2022.856046

ISSN=1664-8021

ABSTRACT=Lymphatic malformation-6 (LMPHM6) is a rarer form of non-immune hydrops, that often manifests as widespread lymphedema involving all segments of the body, such as subcutaneous oedema, intestinal/pulmonary lymphangiectasia, chylothoraces and pleural/pericardial effusions. Here, we detected one rare and previously unobserved homozygous missense variant in PIEZO1 (c.5162 C>G, p. Ser1721Trp) as a novel genetic cause of autosomal recessive LMPHM6, in a family with three adverse pregnancy outcomes due to non-immune fetal hydrops. Although, loss of function mutations usually including nonsense, frameshift, splice site, and also fewer missense variants  in PIEZO1 have been proved to lead to LMPHM6, among which, biallelic homozygous mutations resulting in the loss of function of PIEZO1  have not been reported before. Here, we first strongly implicated impaired PIEZO1 function associated LMPHM6 with a homozygous missense mutation in PIEZO1.