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Here, we present seven previously unreported individuals carrying de novo 3q27 deletions (under 5\u2009Mb), which include the\n                    <jats:italic>AP2M1<\/jats:italic>\n                    (adaptor\u2010related protein complex 2, mu\u20101 subunit) gene and summarize data from 12 previously reported cases from the literature. The overall cohort of 19 individuals demonstrates almost universal intrauterine growth restriction, intellectual disability, and post\u2010natal microcephaly, along with common features of hypotonia, post\u2010natal short stature, and facial dysmorphisms. Newly identified features include bicuspid aortic valve, atrial septal defect, congenital malformation of the mesentery, and metopic craniosynostosis, present in a subset of individuals. These seven newly identified individuals allow narrowing of the previously reported smallest region of overlap to 430\u2009kb at 3q27.1. This region includes 20 protein coding genes. We propose\n                    <jats:italic>AP2M1<\/jats:italic>\n                    as the most likely contributor to the neurodevelopmental phenotype, based on its predicted intolerance to haploinsufficiency, functional evidence in murine models, and similar phenotypes associated with other adaptor\u2010protein\u2010complex\u2010family members. Furthermore, we report the first individual with a de novo loss\u2010of\u2010function nonsense single nucleotide variant in\n                    <jats:italic>AP2M1<\/jats:italic>\n                    with neurodevelopmental features including severe epilepsy. We discuss the implications of this finding in the context of previously reported epileptic encephalopathy in individuals with the recurrent p.Arg170Trp variant in\n                    <jats:italic>AP2M1<\/jats:italic>\n                    . In conclusion, our study expands the phenotypic spectrum of 3q27 microdeletions and highlights the potential importance of\n                    <jats:italic>AP2M1<\/jats:italic>\n                    in its clinical presentation.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.64153","type":"journal-article","created":{"date-parts":[[2025,7,9]],"date-time":"2025-07-09T13:03:30Z","timestamp":1752066210000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["<i>AP2M1<\/i>\n                    Is a Candidate Gene for Microcephaly and Intellectual Disability in 3q27.1 Deletions"],"prefix":"10.1002","volume":"197","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5378-6746","authenticated-orcid":false,"given":"Russell","family":"Gear","sequence":"first","affiliation":[{"name":"Victorian Clinical Genetics Services  Melbourne Australia"},{"name":"Murdoch Children's Research Institute  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5569-0609","authenticated-orcid":false,"given":"Paul","family":"Kalitsis","sequence":"additional","affiliation":[{"name":"Victorian Clinical Genetics Services  Melbourne Australia"},{"name":"Murdoch Children's Research Institute  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Glass","sequence":"additional","affiliation":[{"name":"Victorian Clinical Genetics Services  Melbourne Australia"},{"name":"Murdoch Children's Research Institute  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertrand","family":"Isidor","sequence":"additional","affiliation":[{"name":"University Hospital Nantes  Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Vincent\u2010Delorme","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Arras  Arras France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1368-1023","authenticated-orcid":false,"given":"Florence","family":"Petit","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire de Lille  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0340-3433","authenticated-orcid":false,"given":"Judith M. A.","family":"Verhagen","sequence":"additional","affiliation":[{"name":"Erasmus University Medical Center Rotterdam  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2567-7360","authenticated-orcid":false,"given":"Alexander","family":"Jorge","sequence":"additional","affiliation":[{"name":"Human Genome and Stem\u2010Cell Research Center, Institute of Biosciences, Department of Genetics and Evolutionary Biology University of S\u00e3o Paulo  S\u00e3o Paulo Brazil"},{"name":"Genetic Endocrinology Unit University of Sao Paulo  Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2931-8605","authenticated-orcid":false,"given":"Ana Cristina Victorino","family":"Krepischi","sequence":"additional","affiliation":[{"name":"Human Genome and Stem\u2010Cell Research Center, Institute of Biosciences, Department of Genetics and Evolutionary Biology University of S\u00e3o 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