Translational Medicine Center, Chinese PLA General Hospital, 28 Fuxing Road, 100853, Beijing, People's Republic of China.
State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, School of Life Sciences, Tsinghua University, 30 Shuangqing Road, 100084, Beijing, People's Republic of China.
J Hum Genet. 2020 Nov;65(11):1039-1043. doi: 10.1038/s10038-020-0804-0. Epub 2020 Jul 12.
Meckel-Gruber syndrome (MKS) is a clinically and genetically heterogeneous ciliopathy characterized by a triad of occipital encephalocele, polycystic kidneys, and postaxial polydactyly. Pathogenesis of MKS is related to dysfunction of primary cilia. However, reports on MKS caused by Tectonic2 (TCTN2) mutations are scanty whilst. There is no direct evidence of ciliogenesis in such MKS patients. Here, we identified two novel nonsense variants of TCTN2 (c.343G > T, p.E115*; c.1540C > T, p.Q514*) in a Chinese MKS fetus. Compared to reported TCTN2-causing MKS patients, our case represented an endocardial pad defect, which was not reported previously. We also found primary cilia protruded normally from the surface of epithelial cells in the affected fetal kidney tubules compared to controls, indicating TCTN2 is not necessary for ciliogenesis in the kidney. To our knowledge, this is the first case of MKS fetus caused by TCTN2 mutations from China.
Meckel-Gruber 综合征（MKS）是一种临床表现和遗传异质性的纤毛病，其特征为枕部脑膨出、多囊肾和轴后多指（趾）。MKS 的发病机制与初级纤毛功能障碍有关。然而，关于 Tectonic2（TCTN2）突变引起的 MKS 的报道很少，而此类 MKS 患者的纤毛发生尚无直接证据。在此，我们在一名中国 MKS 胎儿中鉴定出 TCTN2 的两个新的无义变异（c.343G>T，p.E115*；c.1540C>T，p.Q514*）。与已报道的 TCTN2 引起的 MKS 患者相比，我们的病例表现为心内膜垫缺损，这是以前未曾报道过的。我们还发现，与对照组相比，受影响的胎儿肾小管上皮细胞表面的初级纤毛正常伸出，表明 TCTN2 对于肾脏的纤毛发生不是必需的。据我们所知，这是首例来自中国的由 TCTN2 突变引起的 MKS 胎儿病例。
