PRDM9 Deficiency Drives Mosaic Promoter Deletions in Sporadic Hirschsprung Disease and Supports Blood-based Molecular Stratification

The authors investigate the role of PRDM9 deficiency in sporadic Hirschsprung disease (HSCR) and its potential as a blood-based biomarker for molecular stratification. They find that PRDM9 loss leads to mosaic promoter deletions and impaired enteric neuronal differentiation, which correlates with transcriptional repression in a significant subgroup of HSCR patients. Their findings suggest that a blood MPD score can effectively distinguish HSCR from controls, highlighting a non-invasive approach for molecular stratification in this condition.