The first and second authors contributed equally to this manuscript.
Analysis of RET, ZEB2, EDN3 and GDNF Genomic Rearrangements in 80 Patients with Hirschsprung Disease (Using multiplex ligation-dependent probe amplification)
Article first published online: 28 JAN 2009
© 2008 The Authors. Journal compilation © 2008 Blackwell Publishing Ltd/University College London
Annals of Human Genetics
Volume 73, Issue 2, pages 147–151, March 2009
How to Cite
Serra, A., Görgens, H., Alhadad, K., Ziegler, A., Fitze, G. and Schackert, H. K. (2009), Analysis of RET, ZEB2, EDN3 and GDNF Genomic Rearrangements in 80 Patients with Hirschsprung Disease (Using multiplex ligation-dependent probe amplification). Annals of Human Genetics, 73: 147–151. doi: 10.1111/j.1469-1809.2008.00503.x
- Issue published online: 17 FEB 2009
- Article first published online: 28 JAN 2009
- Received: 19 October 2008Accepted: 4 December 2008
- Hirschsprung disease;
- genomic rearrangements;
- RET proto-oncogene;
- multiplex ligation-dependent probe amplification
Hirschsprung disease (HSCR) is transmitted in a complex pattern of inheritance and is mostly associated with variants in the RET proto-oncogene. However, RET mutations are only identified in 15–20% of sporadic HSCR cases and solely in 50% of the familial cases. Since genomic rearrangements in particularly sensitive areas of the RET proto-oncogene and/or associated genes may account for the HSCR phenotype in patients without other detectable RET variants, the aim of the present study was to identify rearrangements in the coding sequence of RET as well as in three HSCR-associated genes (ZEB2, EDN3 and GDNF) in HSCR patients by using Multiplex Ligation-dependent Probe Amplification (MLPA). We have screened 80 HSCR patients for genomic rearrangements in RET, ZEB2, EDN3 and GDNF and did not identify any deletion or amplification in these four genes in all patients. We conclude that genomic rearrangements in RET are rare and were not responsible for the HSCR phenotype in individuals without identifiable germline RET variants in our group of patients, yet this possibility cannot be excluded altogether because the confidence to identify variation in at least two percent of the individuals was only 95%.