Abstract
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.
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Acknowledgements
We thank all patients and family members involving in this study. This work is supported by the Beijing Natural Science Foundation (7184243) and the Chinese PLA General Hospital Translational Medicine Foundation (2018TM-11) in the design, collection, analysis and the writing of the article. We thank Dr. Junnian Zhou (Beijing Institute of Radiation Medicine; South China Research Center for Stem Cell & Regenerative Medicine, SCIB, China) for editing a draft of the paper.
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Zhang, M., Chang, Z., Tian, Y. et al. Two novel TCTN2 mutations cause Meckel–Gruber syndrome. J Hum Genet 65, 1039–1043 (2020). https://doi.org/10.1038/s10038-020-0804-0
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DOI: https://doi.org/10.1038/s10038-020-0804-0
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