Rectal organoid morphology analysis (ROMA) as a promising diagnostic tool in cystic fibrosis

Diagnosing cystic fibrosis (CF) when sweat chloride is not in the CF range and less than 2 disease-causing CFTR mutations are found requires physiological CFTR assays, which are not always feasible or available. We developed a new physiological CFTR assay based on the morphological differences between rectal organoids from subjects with and without CF. In organoids from 167 subjects with and 22 without CF, two parameters derived from a semi-automated image analysis protocol (rectal organoid morphology analysis, ROMA) fully discriminated CF subjects with two disease-causing mutations from non-CF subjects (p<0.001). ROMA, feasible at all ages, can be centralised to improve standardisation.

Automated summary

The new physiological CFTR assay, ROMA, based on rectal organoid morphology analysis, is able to accurately differentiate CF patients with disease-causing mutations from non-CF subjects. It offers improved diagnostic accuracy and can be used across all age groups.