Abstract
Xeroderma pigmentosum (XP) and Cockayne syndrome (CS) are rare autosomal recessive DNA repair disorders. XP is characterized by extreme sensitivity to UV radiation and a very high risk of skin cancer. To date, little is known about the clinical characteristics and genetic basis of these diseases in Russia. Here, we present a detailed study of 14 patients (aged 6–30 years) from 11 unrelated families of diverse ethnic backgrounds. Using a multigene panel or whole-genome sequencing, we identified patients with homozygous or compound heterozygous variants in XPC (n = 8), XPA (n = 4), DDB2 (n = 1), and ERCC6 (n = 1). Two XP and one CS cases were presented in one family. A total of 110 relatives were screened to determine carrier status. Skin cancer was revealed in 100% of the 13 XP patients; the median age at first manifestation was 13 years (range 5–23). Basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma developed in 10, 7, and 3 patients, respectively. All three cancer types occurred in two patients. The patients underwent surgical treatment; additionally, two patients with BCC received targeted therapy (vismodegib, sonidegib). Anti-PD-1 immunotherapy was administered successfully in three patients with multiple or advanced skin tumors.