A loss‐of‐function mutation p.T256M in NDRG4 is implicated in the pathogenesis of pulmonary atresia with ventricular septal defect (PA/VSD) and tetralogy of Fallot (TOF)
| العنوان: | A loss‐of‐function mutation p.T256M in NDRG4 is implicated in the pathogenesis of pulmonary atresia with ventricular septal defect (PA/VSD) and tetralogy of Fallot (TOF) |
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| المؤلفون: | Jian Wang, Sun Chen, Shuang Zhou, Wenting Song, Alex F. Chen, Yue Zhou, Jiayu Peng, Kun Sun, Qingjie Wang, Zhuo Meng |
| المصدر: | FEBS Open Bio, Vol 11, Iss 2, Pp 375-385 (2021) FEBS Open Bio |
| بيانات النشر: | Wiley, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Heart disease, DNA Mutational Analysis, Muscle Proteins, Pathogenesis, 0302 clinical medicine, Loss of Function Mutation, PA/VSD, Medicine, Myocytes, Cardiac, lcsh:QH301-705.5, Research Articles, Cells, Cultured, Tetralogy of Fallot, TOF, p27, G2 Phase Cell Cycle Checkpoints, medicine.anatomical_structure, 030220 oncology & carcinogenesis, cardiovascular system, Cardiology, Female, Pulmonary atresia, Research Article, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, cardiac myocytes, proliferation, Primary Cell Culture, Nerve Tissue Proteins, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Internal medicine, medicine.artery, Exome Sequencing, Humans, NDRG4, cardiovascular diseases, Pathological, Cell Proliferation, business.industry, Heart Septal Defects, Infant, Blood flow, Embryo, Mammalian, medicine.disease, G1 Phase Cell Cycle Checkpoints, 030104 developmental biology, lcsh:Biology (General), Pulmonary Atresia, Ventricle, Pulmonary artery, business |
| الوصف: | N‐myc downstream‐regulated gene (NDRG)4 is widely expressed in human embryonic hearts. The p.T256M variant in NDRG4 resulted in G1 and G2 arrest of human cardiac myocytes, thereby impairing their proliferative ability, which likely contributes towards the pathogenesis of pulmonary atresia with ventricular septal defect and tetralogy of Fallot. Pulmonary atresia with ventricular septal defect (PA/VSD) is a rare congenital heart disease (CHD) characterized by a lack of luminal continuity and blood flow from either the right ventricle or the pulmonary artery, together with VSDs. The prevalence of PA/VSD is about 0.2% of live births and approximately 2% of CHDs. PA/VSD is similar to tetralogy of Fallot (TOF) in terms of structural and pathological characteristics. The pathogenesis of these two CHDs remains incompletely understood. It was previously reported that N‐myc downstream‐regulated gene (NDRG)4 is required for myocyte proliferation during early cardiac development. In the present study, we enrolled 80 unrelated patients with PA/VSD or TOF and identified a probably damaging variant p.T256M of NDRG4. The p.T256M variant impaired the proliferation ability of human cardiac myocytes (hCM). Furthermore, the p.T256M variant resulted in G1 and G2 arrest of hCM, followed by an increase in p27 and caspase‐9 expression. Our results provide evidence that the p.T256M variant in NDRG4 is a pathogenic variant associated with impaired hCM proliferation and cell‐cycle arrest and likely contributes towards the pathogenesis of PA/VSD and TOF. |
| تدمد: | 2211-5463 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a5ac7afd408751b72b1d0642286aea89 https://doi.org/10.1002/2211-5463.13044 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....a5ac7afd408751b72b1d0642286aea89 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22115463 |
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