Title: Molecular karyotyping in anorectal malformations: Could DGCR6 gene haploinsufficiency cause anal atresia in 22q11 deletion syndrome? Running Title: Anorectal malformations in 22q11 deletion syndrome

Background/aim: Anorectal malformations (ARM) are classified as multifactorial diseases. The etiology of ARM is still not clear because of the complexity of the pathologic changes. Materials and methods: In the present study, the array-CGH results of 10 patients with ARM not associated with a specific syndrome despite having some additional findings were evaluated. Array-CGH analysis was performed using the 8x60K ISCA, Agilent® microarray platform. Pathogenic CNVs were further confirmed using fluorescence in situ hybridization (FISH) or quantitative real-time polymerase chain reaction (qPCR). Results: Chromosome 22q11.2 deletion was detected in two patients. One of these patients had anal stenosis, minor cardiac abnormalities, and a small 0.89-Mb deletion. The second patient had anal atresia, immune deficiency, inguinal hernia, and a 2.7-Mb cryptic deletion. The overlapping genes in the deletion regions of the two patients were DGCR5, DGCR6 and PRODH . Conclusion: DGCR6 , alters the expression of important genes such as TBX1 and affects neural crest migration. Considering that ARMs are caused by abnormalities in neural crest cell migration, it is thought that these genes may play a role in the etiology of ARM. To our knowledge, this region is one of the smallest interstitial deletions in the chromosome 22q11.2 region to be published to date. Further research on the DGCR6 gene, which may be a candidate gene responsible for anal atresia, will clarify this point. This article been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Reco rd. Please this article as: Ozyavuz P, Kayhan G, Perçin EF. Molecular karyotyping in anorectal malformations: Could DGCR6 gene haploinsufficiency cause anal atresia in 22q11 deletion syndrome?. Erciyes

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