Altered Notch signalling in Dowling-Degos disease: A transcriptomic insight into disease pathogenesis

Dowling-Degos disease (DDD) is a rare autosomal-dominant hyperpigmentation disorder caused by mutations in KRT5, POFUT1, POGLUT1 and PSENEN. Our results suggest that dysfunctional Notch signaling in melanocytes plays a key role in DDD pathogenesis, and that altered biogenesis and intracellular trafficking of melanosomes, receptor tyrosine kinases signaling, and ESR-mediated signaling may represent downstream molecular mechanisms through which decreased Notch signaling leads to hyperpigmentation in DDD. Furthermore, a common downstream pathomechanism for both, POGLUT1 and PSENEN mutation carriers can be assumed.