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Previously, we found that genetic ablation of <jats:italic>Fzr1<\/jats:italic> promotes the death of neural progenitor cells leading to neurogenesis impairment and microcephaly in mouse. To ascertain the possible translation of these findings in humans, we searched for mutations in the <jats:italic>Fzr1<\/jats:italic> gene in 390 whole exomes sequenced <jats:italic>in trio<\/jats:italic> in individuals showing neurodevelopmental disorders compatible with a genetic origin. We found a novel missense (p.Asp187Gly) <jats:italic>Fzr1<\/jats:italic> gene mutation (c.560A&gt;G) in a heterozygous state in a 4\u2010year\u2010old boy, born from non\u2010consanguineous Spanish parents, who presents with severe antenatal microcephaly, psychomotor retardation, and refractory epilepsy. Cdh1 protein levels in leucocytes isolated from the patient were significantly lower than those found in his parents. Expression of the Asp187Gly mutant form of Cdh1 in human embryonic kidney 293T cells produced less Cdh1 protein and APC\/C activity, resulting in altered cell cycle distribution when compared with cells expressing wild\u2010type Cdh1. Furthermore, ectopic expression of the Asp187Gly mutant form of Cdh1 in cortical progenitor cells in primary culture failed to abolish the enlargement of the replicative phase caused by knockout of endogenous Cdh1. These results indicate that the loss of function of APC\/C\u2010Cdh1 caused by Cdh1 Asp187Gly mutation is a new cause of prenatal microcephaly, psychomotor retardation, and severe epilepsy.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc14828-fig-0005-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/doi.org\/10.1111\/jnc.14835\">Read the Editorial Highlight for this article on page 8<\/jats:ext-link>.<\/jats:p><jats:p>Cover Image for this issue: doi: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1111\/jnc.14524\">10.1111\/jnc.14524<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.14828","type":"journal-article","created":{"date-parts":[[2019,7,18]],"date-time":"2019-07-18T18:28:28Z","timestamp":1563474508000},"page":"103-115","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["A novel human Cdh1 mutation impairs anaphase promoting complex\/cyclosome activity resulting in microcephaly, psychomotor retardation, and epilepsy"],"prefix":"10.1111","volume":"151","author":[{"given":"Cristina","family":"Rodr\u00edguez","sequence":"first","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca, Hospital Universitario de Salamanca, CSIC  Universidad de Salamanca Salamanca Spain"},{"name":"Instituto de Biolog\u00eda Funcional y Gen\u00f3mica, CSIC Universidad de Salamanca Salamanca Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"S\u00e1nchez\u2010Mor\u00e1n","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca, Hospital Universitario de Salamanca, CSIC  Universidad de Salamanca Salamanca Spain"},{"name":"Instituto de Biolog\u00eda Funcional y Gen\u00f3mica, CSIC Universidad de Salamanca Salamanca Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Gen\u00f3mica y Medicina NIMGenetics Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar","family":"Tirado","sequence":"additional","affiliation":[{"name":"Departamento de Neuropediatr\u00eda Hospital Universitario La Paz Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel 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