Research Summary

Training Programme: ‘Correlating Patterns of the Genotypic Variations in RET Gene with the Phenotype of Hirschsprung Disease(HD) in the Indian Cohort’


Hirschsprung’s disease(HD) is a congenital intestinal disorder characterized by absence of ganglion cells (aganglionosis) in the enteric nervous system of variable portions of colon and rectum leading to three phenotypes, namely short segment (upto sigmoid colon,80%,males), long segment (upto caecum,17%,females) and total colonic aganglionosis (3%). It is one of the neurocristopathies occurring due to deranged neural crest development resulting in impaired intestinal motility, neonatal intestinal obstruction and lethal intestinal perforation. Its incidence varies from 1/10,000 livebirths in Hispanics to 2.8/10,000 livebirths in Asians (Indians not included).


Of all the genes, defects in the RET gene play a major role with 50% being familial and 7%-35% sporadic. However, we have no such genomics data available in our population. This proposal is attempting to study the involvement of the RET gene in our HD cohort and correlating this with the phenotype of HD. It has a functional significance which is essential for understanding the pathogenesis of the disease, to estimate penetrance and recurrence risk rates. We are also exploring the development of model systems to understand the biology of neural crest cells and to analyse the function of the RET gene. 

Figure Legend: Diagnostic modalities of Hirschsprung disease and genotypic workup to study associated RET gene variations