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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\u2010myc downstream\u2010regulated 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\u20109 expression. Our results provide evidence that the p.T256M variant in NDRG4 is a pathogenic variant associated with impaired hCM proliferation and cell\u2010cycle arrest and likely contributes towards the pathogenesis of PA\/VSD and TOF.<\/jats:p>","DOI":"10.1002\/2211-5463.13044","type":"journal-article","created":{"date-parts":[[2020,11,20]],"date-time":"2020-11-20T05:51:59Z","timestamp":1605851519000},"page":"375-385","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A loss\u2010of\u2010function mutation p.T256M in NDRG4 is implicated in the pathogenesis of pulmonary atresia with ventricular septal defect (PA\/VSD) and tetralogy of Fallot (TOF)"],"prefix":"10.1002","volume":"11","author":[{"given":"Jiayu","family":"Peng","sequence":"first","affiliation":[{"name":"Department of Pediatric Cardiology Xinhua Hospital School of Medicine Shanghai Jiao Tong University Shanghai 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