Abrocitinib alleviates the symptoms of Netherton syndrome and is well tolerated.

Purpose: To investigate the potential genetic basis of Netherton syndrome (NS) through first- and second-generation DNA sequencing techniques. Additionally, we evaluated the therapeutic efficacy of Abrocitinib in NS patients.

Materials and methods: We conducted whole-exome sequencing analysis on a pedigree comprising one affected individual with NS. Subsequently, the identified patient was treated with Abrocitinib, and clinical improvements in cutaneous manifestations were systematically assessed.

Results: Genetic analysis revealed that the patient harbored compound heterozygous mutations in the SPINK5 gene, including a missense mutation in exon 26 (c.2475G > T, p.Trp825Cys). Following six months of Abrocitinib therapy, the patient exhibited marked improvement in skin rash and overall disease severity.

Conclusions: Our findings suggest that SPINK5 missense mutations may contribute to the pathogenesis of NS. Furthermore, Abrocitinib demonstrates promising therapeutic potential in the management of NS, warranting further investigation in larger clinical cohorts.