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In around 50% of patients, the malformation is isolated, while in the remainder it arises within the context of complex genetic abnormalities or a defined genetic syndrome. Recent studies have implicated rare copy number variations (CNVs) in both isolated and nonisolated ARM, and identified plausible candidate genes. Methods: In the present study, array\u2010based molecular karyotyping was performed to identify causative CNVs in 32 sporadic ARM patients with comorbid abnormalities of the central nervous system (CNS). This phenotype was selected to enrich for rare CNVs, since previous research has implicated rare CNVs in both CNS abnormalities and ARM. Results: In five patients, a probable disease\u2010causing CNV was identified (del6q14.3q16.3, del14q32.2, del17q12q21.2, and two patients with del22q11.21). In three of these patients, the CNVs were de novo. For the remaining two patients, no parental DNA was available. Deletions at 22q11.21 and 6q14.3 have been associated with both CNS abnormalities and ARM. In contrast, deletions at 14q32.2 have only been described in patients with CNS abnormalities, and the del17q12q21.2 is a novel CNV. Expression studies in mice suggest that<jats:italic>NEUROD2<\/jats:italic>and<jats:italic>RARA<\/jats:italic>, which reside within the newly identified del17q12q21.2 region, are candidate genes for the formation of microcephaly and ARM. Conclusion: The present data suggest that CNVs are a frequent cause of the ARM with CNS abnormalities phenotype, and that array\u2010analysis is indicated in such patients. Birth Defects Research (Part A) 103:235\u2013242, 2015. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/bdra.23321","type":"journal-article","created":{"date-parts":[[2014,9,24]],"date-time":"2014-09-24T06:43:04Z","timestamp":1411540984000},"page":"235-242","source":"Crossref","is-referenced-by-count":21,"title":["Genome\u2010wide mapping of copy number variations in patients with both anorectal malformations and central nervous system abnormalities"],"prefix":"10.1002","volume":"103","author":[{"given":"Gabriel C.","family":"Dworschak","sequence":"first","affiliation":[{"name":"Institute of Human Genetics, University of Bonn Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus","family":"Draaken","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University of Bonn Bonn Germany"},{"name":"Department of Genomics, Life and Brain Center University of Bonn Bonn 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