Han Shuai, Guo Xin, Wang Xiaogang, Lin Huijun, Yu Yiqi, Shu Jing, Dong Minyue, Yang Liwei
Center for Reproductive Medicine, Department of Obstetrics, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, China.
Cancer Center, Department of Hematology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, China.
Front Genet. 2022 May 13;13:856046. doi: 10.3389/fgene.2022.856046. eCollection 2022.
Lymphatic malformation-6 (LMPHM6) is a rarer form of nonimmune hydrops that often manifests as widespread lymphedema involving all segments of the body, namely, subcutaneous edema, intestinal/pulmonary lymphangiectasia, chylothoraces, and pleural/pericardial effusions. Here, we detected one rare and previously unobserved homozygous missense variant in (c.5162C>G, p.Ser1721Trp) as a novel genetic cause of autosomal recessive LMPHM6, in a family with three adverse pregnancy outcomes due to nonimmune fetal hydrops. Although, the loss-of-function mutations such as those usually including nonsense, frameshift, splice site, and also fewer missense variants in have been proved to lead to LMPHM6, among these, the 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 .
淋巴管畸形6型（LMPHM6）是一种较为罕见的非免疫性水肿形式，常表现为累及身体所有部位的广泛性淋巴水肿，即皮下水肿、肠道/肺淋巴管扩张、乳糜胸以及胸腔/心包积液。在此，我们在一个因非免疫性胎儿水肿导致三次不良妊娠结局的家族中，检测到一个罕见且先前未观察到的纯合错义变异（c.5162C>G，p.Ser1721Trp），作为常染色体隐性LMPHM6的一种新的遗传病因。尽管功能丧失性突变，如通常包括无义、移码、剪接位点突变，以及较少的错义变异，已被证明可导致LMPHM6，但其中导致PIEZO1功能丧失的双等位基因纯合突变此前尚未见报道。在此，我们首次有力地证明了与PIEZO1功能受损相关的LMPHM6与一个纯合错义突变有关。
