Impairment of Notch 1 Signaling Is a Common Defect in Lesions From Patients With Hidradenitis Suppurativa

The study investigated the impairment of notch1 signaling in patients with hidradenitis suppurativa (HS), focusing on a family with a new NCSTN gene mutation. The mutation led to reduced levels of mutated NCSTN transcripts and an abnormal notch-1 protein expression pattern in lesional skin. Notch-1 and notch-2 protein expressions were decreased, with a significant reduction in notch1-induced gene transcripts in mutated patients compared to healthy individuals. The study found that the impairment was due to haploinsufficiency rather than a dominant negative effect. Additionally, similar notch1 signaling defects were observed in HS cases without GS gene mutations. This research demonstrated that notch1 signaling was severely impaired in HS, affecting keratinocytes and hair follicle cells, regardless of the presence of NCSTN or other GS gene mutations.