MUTYH-Associated Polyposis: The Irish Experience>.

Area of Science:

• Genetics and Genomics
• Oncology
• Molecular Biology

Background:

• MUTYH gene mutations are implicated in DNA repair.
• Bi-allelic MUTYH mutations predispose individuals to polyposis and gastrointestinal cancers, distinct from familial adenomatous polyposis coli.
• Two common European MUTYH mutations explain 90% of MUTYH-associated polyposis (MAP).

Purpose of the Study:

• To investigate the incidence of MUTYH-associated polyposis (MAP) in Ireland.
• To identify individuals with bi-allelic MUTYH mutations and their associated phenotypes.
• To assess the diagnostic rate and regional distribution of MAP in Ireland.

Main Methods:

• Retrospective cohort study of patients undergoing MUTYH testing between 2003 and 2016.
• Electronic database searches using "MUTYH" and "MYH" terms.
• Chart review for phenotypic and genotypic data, confirming bi-allelic mutations.

Main Results:

• Twenty-six individuals (17 families) with bi-allelic MUTYH mutations were identified.
• Of these, 62% developed colorectal malignancies and 85% had polyposis.
• Eleven families carried bi-allelic status for common European mutations, with regional variation noted in carriers.

Conclusions:

• MAP is under-diagnosed in the Irish population.
• Increased awareness is crucial for early identification and surveillance of individuals with bi-allelic MUTYH mutations.
• Targeted screening and surveillance can improve outcomes for colorectal pathology in MAP patients.