Fabian, Julia and Dworschak, Gabriel C. and Waffenschmidt, Lea and Schierbaum, Luca and Bendixen, Charlotte and Heilmann-Heimbach, Stefanie and Sivalingam, Sugirthan and Buness, Andreas and Schwarzer, Nicole and Boemers, Thomas M. and Schmiedeke, Eberhard and Neser, Jorg and Leonhardt, Johannes and Kosch, Ferdinand and Weih, Sandra and Gielen, Helen Maya and Hosie, Stuart and Kabs, Carmen and Palta, Markus and Maerzheuser, Stefanie and Bode, Lena Marie and Lacher, Martin and Schaefer, Frank-Mattias and Stehr, Maximilian and Knorr, Christian and Ure, Benno and Kleine, Katharina and Rolle, Udo and Zaniew, Marcin and Phillip, Grote and Zwink, Nadine and Jenetzky, Ekkehart and Reutter, Heiko and Hilger, Alina C. (2023) Genome-wide identification of disease-causing copy number variations in 450 individuals with anorectal malformations. EUROPEAN JOURNAL OF HUMAN GENETICS, 31 (1). pp. 105-111. ISSN 1018-4813, 1476-5438
Full text not available from this repository. (Request a copy)Abstract
Anorectal malformations (ARM) represent a spectrum of rare malformations originating from a perturbated development of the embryonic hindgut. Approximately 60% occur as a part of a defined genetic syndrome or within the spectrum of additional congenital anomalies. Rare copy number variations (CNVs) have been associated with both syndromic and non-syndromic forms. The present study represents the largest study to date to explore the contribution of CNVs to the expression of ARMs. SNP-array-based molecular karyotyping was applied in 450 individuals with ARM and 4392 healthy controls. CNVs were identified from raw intensity data using PennCNV. Overlapping CNVs between cases and controls were discarded. Remaining CNVs were filtered using a stringent filter algorithm of nine filter steps. Prioritized CNVs were confirmed using qPCR. Filtering prioritized and qPCR confirmed four microscopic chromosomal anomalies and nine submicroscopic CNVs comprising seven microdeletions (del2p13.2, del4p16.2, del7q31.33, del9p24.1, del16q12.1, del18q32, del22q11.21) and two microduplications (dup2p13.2, dup17q12) in 14 individuals (12 singletons and one affected sib-pair). Within these CNVs, based on their embryonic expression data and function, we suggest FOXK2, LPP, and SALL3 as putative candidate genes. Overall, our CNV analysis identified putative microscopic and submicroscopic chromosomal rearrangements in 3% of cases. Functional characterization and re-sequencing of suggested candidate genes is warranted.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | VATER/VACTERL; ORGANIZATION; DATABASE |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Kinder- und Jugendmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 05 Mar 2024 07:40 |
| Last Modified: | 05 Mar 2024 07:40 |
| URI: | https://pred.uni-regensburg.de/id/eprint/58795 |
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