A novel study of Copy Number Variations in Hirschsprung disease using the Multiple Ligation-dependent Probe Amplification (MLPA) technique

作者：Nunez Torres Rocio; Fernandez Raquel M; Lopez Alonso Manuel; Antinolo Guillermo; Borrego Salud^*

来源：BMC Medical Genetics, 2009, 10(1): 119.

DOI：10.1186/1471-2350-10-119

Background: Hirschsprung disease (HSCR) is a congenital malformation of the hindgut produced by a disruption in neural crest cell migration during embryonic development. HSCR has a complex genetic etiology and mutations in several genes, mainly the RET proto-oncogene, have been related to the disease. There is a clear predominance of missense/nonsense mutations in these genes whereas copy number variations (CNVs) have been seldom described, probably due to the limitations of conventional techniques usually employed for mutational analysis.
Methods: In this study we have aimed to analyze the presence of CNVs in some HSCR genes (RET, EDN3, GDNF and ZFHX1B) using the Multiple Ligation-dependent Probe Amplification (MLPA) approach.
Results: Two alterations in the MLPA profiles of RET and EDN3 were detected, but a detailed inspection showed that the decrease in the corresponding dosages were due to point mutations affecting the hybridization probes regions.
Conclusion: Our results indicate that CNVs of the gene coding regions analyzed here are not a common molecular cause of Hirschsprung disease. However, further studies are required to determine the presence of CNVs affecting non-coding regulatory regions, as well as other candidate genes.

• 出版日期2009-11-19