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The clinical findings included a prenatal presentation of microcephaly, polyhydramnios and clenched hands while postnatal findings included microcephaly, severe developmental delay, dysmorphism, neurologic deficits, and death in infancy. A shared rare homozygous, missense variant (c.274A\u2009&gt;\u2009G; p.Ser92Gly, NM_024516.4) was identified in <jats:italic>PAGR1,<\/jats:italic> a gene currently not associated with a Mendelian disease. <jats:italic>PAGR1<\/jats:italic> encodes a component of the histone methyltransferase MLL2\/MLL3 complex and may function in the DNA damage response pathway. Complete knockout of the murine <jats:italic>Pagr1a<\/jats:italic> is embryonic\u2010lethal. Given the available evidence, <jats:italic>PAGR1<\/jats:italic> is a strong candidate gene for a novel autosomal recessive severe syndromic neurodevelopmental disorder.<\/jats:p>","DOI":"10.1002\/ajmg.a.62513","type":"journal-article","created":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T20:25:51Z","timestamp":1632947151000},"page":"336-342","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Bi\u2010allelic <scp><i>PAGR1<\/i><\/scp> variants are associated with microcephaly and a severe neurodevelopmental disorder: Genetic evidence from two families"],"prefix":"10.1002","volume":"188","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8318-3599","authenticated-orcid":false,"given":"Hagit","family":"Daum","sequence":"first","affiliation":[{"name":"Department of Genetics, Hadassah Medical Organization and Faculty of Medicine Hebrew University of Jerusalem  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