{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:09:16Z","timestamp":1790694556928,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,11,7]],"date-time":"2019-11-07T00:00:00Z","timestamp":1573084800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Agenesis of the corpus callosum (ACC) is a common prenatally\u2010detected brain anomaly. Recently, an association between mutations in the <jats:italic>DCC Netrin 1 receptor<\/jats:italic> (<jats:italic>DCC<\/jats:italic>) gene and ACC, with or without mirror movements, has been demonstrated. In this manuscript, we present a family with a novel heterozygous frameshift mutation in <jats:italic>DCC<\/jats:italic>, review the available literature, and discuss the challenges involved in the genetic counseling for recently discovered disorders with paucity of medical information. We performed whole exome sequencing in a healthy nonconsanguineous couple that underwent two pregnancy terminations due to prenatal diagnosis of ACC. A heterozygous variant c.2774dupA (p.Asn925Lysfs*17) in the <jats:italic>DCC<\/jats:italic> gene was demonstrated in fetal and paternal DNA samples, as well as in a healthy 4\u2010year\u2010old offspring. When directly questioned, both father and child reported having mirror movements not affecting quality of life. Segregation analysis demonstrated the variant in three paternal siblings, two of them having mirror movements. Brain imaging revealed normal corpus callosum. Summary of literature data describing heterozygous loss\u2010of\u2010function variants in <jats:italic>DCC<\/jats:italic> (<jats:italic>n<\/jats:italic> = 61) revealed 63.9% penetrance for mirror movements, 9.8% for ACC, and 5% for both. No significant neurodevelopmental abnormalities were reported among the seven published patients with <jats:italic>DCC<\/jats:italic> loss\u2010of\u2010function variants and ACC. Prenatal diagnosis of ACC should prompt a specific anamnesis regarding any neurological disorder, as well as intentional physical examination of both parents aimed to detect mirror movements. In suspicious cases, detection of <jats:italic>DCC<\/jats:italic> pathogenic variants might markedly improve the predicted prognosis, alleviate the parental anxiety, and possibly prevent pregnancy termination.<\/jats:p>","DOI":"10.1002\/ajmg.a.61404","type":"journal-article","created":{"date-parts":[[2019,11,7]],"date-time":"2019-11-07T12:10:25Z","timestamp":1573128625000},"page":"205-212","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["A novel heterozygous loss\u2010of\u2010function <i>DCC<\/i> Netrin 1 receptor variant in prenatal agenesis of corpus callosum and review of the literature"],"prefix":"10.1002","volume":"182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0883-2130","authenticated-orcid":false,"given":"Lena","family":"Sagi\u2010Dain","sequence":"first","affiliation":[{"name":"Genetics Institute, Carmel Medical Center, Affiliated to the Ruth and Bruce Rappaport Faculty of Medicine Technion \u2013 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