Advanced paternal age-related germline mutations in the offspring with neurodevelopmental disorders:An update
With the rapid development of social economy and changed concept of reproduction,childbirth at an advanced age is on a steadily upward trend.However,advanced paternal age(APA)at conception may lead to potential health problems and increase the risk of neurodevelopmental disorders(NDDs)in the offspring.Aging-related free radical damage can cause changes and accumula-tion in the DNA level and/or epigenetic modifications of the male reproductive system and even spermatozoa,ultimately increasing the risk of NDDs in the offspring.This article reviews the epidemiology of NDDs,de novo mutations in the germline,selective accumula-tion of NDDs-related mutations,and epigenetic modifications,which are all associated with APA.The causes of NDDs are complicated and diversified,while current studies on APA-induced NDDs in the offspring are mostly restricted to univariate approaches.In-depth explorations are required into the multi-mechanism synergistic effects to provide some evidence for the diagnosis,treatment and further studies of NDDs and other APA-related disorders in the offspring.
advanced paternal ageneurodevelopmental disordersde novo mutationselective accumulationepigenetic modi-fication
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