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World J Gastroenterol. Dec 7, 2011; 17(45): 4937-4944
Published online Dec 7, 2011. doi: 10.3748/wjg.v17.i45.4937
Genetic interactions and modifier genes in Hirschsprung's disease
Adam S Wallace, Richard B Anderson
Adam S Wallace, Richard B Anderson, Department of Anatomy and Cell Biology, University of Melbourne, Melbourne, Victoria 3010, Australia
Author contributions: Wallace AS and Anderson RB co-wrote the review.
Supported by The National Health and Medical Research Council of Australia to Anderson RB: Project grant, No. 509219; and a CDA Fellowship, No. 454773
Correspondence to: Richard B Anderson, PhD, Department of Anatomy and Cell Biology, University of Melbourne, Melbourne, Victoria 3010, Australia. rba@unimelb.edu.au
Telephone: +61-03-83445783 Fax: +61-03-93475219
Received: February 8, 2011
Revised: June 9, 2011
Accepted: June 16, 2011
Published online: December 7, 2011

Hirschsprung’s disease is a congenital disorder that occurs in 1:5000 live births. It is characterised by an absence of enteric neurons along a variable region of the gastrointestinal tract. Hirschsprung’s disease is classified as a multigenic disorder, because the same phenotype is associated with mutations in multiple distinct genes. Furthermore, the genetics of Hirschsprung’s disease are highly complex and not strictly Mendelian. The phenotypic variability and incomplete penetrance observed in Hirschsprung’s disease also suggests the involvement of modifier genes. Here, we summarise the current knowledge of the genetics underlying Hirschsprung’s disease based on human and animal studies, focusing on the principal causative genes, their interactions, and the role of modifier genes.

Keywords: Neural crest, Enteric nervous system, Hirschsprung’s disease, Aganglionosis, Modifier genes