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Pediatria

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http://hdl.handle.net/10400.17/43

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Browsing Pediatria by Author "Abt, R"

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  • Targeted Gene Panel Sequencing for Early-onset Inflammatory Bowel Disease and Chronic Diarrhea
    Publication . Petersen, BS; August, D; Abt, R; Alddafari, M; Atarod, L; Baris, S; Bhavsar, H; Brinkert, F; Buchta, M; Bulashevska, A; Chee, R; Cordeiro, AI; Dara, N; Dückers, G; Elmarsafy, A; Frede, N; Galal, N; Gerner, P; Glocker, EO; Goldacker, S; Hammermann, J; Hasselblatt, P; Havlicekova, Z; Hübscher, K; Jesenak, M; Karaca, NE; Karakoc-Aydiner, E; Kharaghani, MM; Kilic, SS; Kiykim, A; Klein, C; Klemann, C; Kobbe, R; Kotlarz, D; Laass, MW; Leahy, TR; Mesdaghi, M; Mitton, S; Farela Neves, J; Öztürk, B; Pereira, LF; Rohr, J; Restrepo, JLR; Ruzaike, G; Saleh, N; Seneviratne, S; Senol, E; Speckmann, C; Tegtmeyer, D; Thankam, P; van der Werff ten Bosch, J; von Bernuth, H; Zeissig, S; Zeissig, Y; Franke, A; Grimbacher, B
    Background: In contrast to adult-onset inflammatory bowel disease (IBD), where many genetic loci have been shown to be involved in complex disease etiology, early-onset IBD (eoIBD) and associated syndromes can sometimes present as monogenic conditions. As a result, the clinical phenotype and ideal disease management in these patients often differ from those in adult-onset IBD. However, due to high costs and the complexity of data analysis, high-throughput screening for genetic causes has not yet become a standard part of the diagnostic work-up of eoIBD patients. Methods: We selected 28 genes of interest associated with monogenic IBD and performed targeted panel sequencing in 71 patients diagnosed with eoIBD or early-onset chronic diarrhea to detect causative variants. We compared these results to whole-exome sequencing (WES) data available for 25 of these patients. Results: Target coverage was significantly higher in the targeted gene panel approach compared with WES, whereas the cost of the panel was considerably lower (approximately 25% of WES). Disease-causing variants affecting protein function were identified in 5 patients (7%), located in genes of the IL10 signaling pathway (3), WAS (1), and DKC1 (1). The functional effects of 8 candidate variants in 5 additional patients (7%) are under further investigation. WES did not identify additional causative mutations in 25 patients. Conclusions: Targeted gene panel sequencing is a fast and effective screening method for monogenic causes of eoIBD that should be routinely established in national referral centers.
    2017Journal article Open access Show more