Issue Cover (October 2019)

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