New mutations associated with Hirschsprung disease

Area of Science:

• Genetics
• Developmental Biology
• Gastroenterology

Background:

• Hirschsprung disease results from failed neural crest cell migration to the gastrointestinal tract, leading to aganglionosis of the myenteric plexus.
• Numerous gene mutations are linked to Hirschsprung disease, with a significant focus on the RET proto-oncogene pathway.

Purpose of the Study:

• To identify and describe novel and known genetic mutations associated with Hirschsprung disease.
• To investigate the prognostic implications of these genetic mutations.

Main Methods:

• Retrospective analysis of patients diagnosed with Hirschsprung disease.
• Genetic studies were performed on patients evaluated between 1970 and 2013.

Main Results:

• Twenty-one positive genetic studies were identified.
• Seventeen studies involved mutations in the RET proto-oncogene.
• Two novel RET proto-oncogene mutations, previously unreported, were discovered.

Conclusions:

• The RET proto-oncogene is the primary genetic factor implicated in Hirschsprung disease.
• Undiscovered mutations continue to contribute to the disease's pathogenesis.
• Genetic testing for the RET proto-oncogene is essential for all Hirschsprung disease patients and their relatives, particularly if associated with MEN2A/MEN2B syndromes.