Journal of NeurochemistryVolume 151, Issue 1 Issue CoverFree Access Issue Cover (October 2019) First published: 10 October 2019 https://doi.org/10.1111/jnc.14524 Read the full article: ‘A novel human Cdh1 mutation impairs anaphase promoting complex/cyclosome activity resulting in microcephaly, psychomotor retardation, and epilepsy’ by C. Rodríguez, I. Sánchez-Morán, S. Álvarez, P. Tirado, D.M. Fernández-Mayoralas, B. Calleja-Pérez, Á. Almeida, A. Fernández-Jaén (J. Neurochem. 2019, vol. 151 (1), pp. 103–15) on doi: 10.1111/jnc.14828 AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Graphical Abstract Front cover: Loss of Cdh1, the activator of the anaphase promoting complex/cyclosome (APC/C), promotes microcephaly in mouse. However, as of yet, no Cdh1 variants have been reported to cause microcephaly in humans. Now we identify a de novo mutation (p.Asp187Gly) in Cdh1 in a 4-year-old boy with prenatal microcephaly, psychomotor retardation and epilepsy. Functional studies in the patient leukocytes, in a human cell line and in mouse neural precursor cells revealed that the mutation produces less Cdh1 protein abundance, likely due to nuclear degradation, leading to APC/C inactivation. Our study shows that the Cdh1 Asp187Gly mutation causes APC/C-Cdh1 inactivation, resulting in prenatal microcephaly, psychomotor retardation and severe epilepsy in human. Image content: Confocal microscopy of cultured 293T cells co-expressing the Asp187Gly mutant form of hemagglutinin (HA)-tagged Cdh1mutant and GFP (green fluorescent protein). Cells were immunolabeled for HA (red immunofluorescent staining). Nuclei were stained with DAPI (blue). Image shows that Cdh1 mutant (HA-Cdh1mut) was mainly localized within the nucleus. Read the full article ‘A novel human Cdh1 mutation impairs anaphase promoting complex/cyclosome activity resulting in microcephaly, psychomotor retardation, and epilepsy’ by C. Rodríguez, I. Sánchez-Morán, S. Álvarez, P. Tirado, D.M. Fernández-Mayoralas, B. Calleja-Pérez, Á. Almeida, A. Fernández-Jaén (J. Neurochem. 2019, vol. 151 (1), pp. 103–15) on doi: 10.1111/jnc.14828 Volume151, Issue1October 2019 RelatedInformation