Clinical Features, Genetics and Treatment in a Russian Cohort of Young Patients with Xeroderma Pigmentosum: A Single Center Experience
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 5–30 years) from 11 unrelated families of diverse ethnic backgrounds. Using a multigene panel or whole-genome sequencing, we identified homozygous or compound heterozygous variants in XPC (8 patients) and XPA (3 patients). In one family with two XP cases, a patient with CS and compound heterozygous ERCC6 variants was identified. In total, 110 family members were screened to determine their carrier status. Skin cancer was revealed in 12/13 (92%) of XP patients, with a median age at diagnosis of 12.5 years (range 5–22). Basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma developed in 10, 6, and 3 patients, respectively. All three cancer types occurred in 2 patients. All patients underwent surgical treatment; additionally, two patients with BCC received targeted therapy (vismodegib, sonidegib). Anti-PD-1 immunotherapy was administered with a favorable clinical response in three patients with advanced SCC or melanoma.
Authors
- Timur Teimurazovich Valiev (ORCID: https://orcid.org/0000-0002-1469-2365)
- Olga V. Bozhko (ORCID: https://orcid.org/0000-0002-4709-9461)
- Елена Вячеславовна Шарапова (ORCID: https://orcid.org/0000-0002-5836-0338)
- Светлана Рафаэлевна Варфоломеева (ORCID: https://orcid.org/0000-0001-6131-1783)
- Татьяна Сергеевна Белышева (ORCID: https://orcid.org/0000-0001-5911-553X)
- Екатерина Евгеньевна Зеленова (ORCID: https://orcid.org/0000-0002-2197-8863)
- Marina Yu. Dorofeeva (ORCID: https://orcid.org/0000-0001-7879-315X)
- Кристина Вячеславовна Орлова (ORCID: https://orcid.org/0000-0002-0442-5917)
- D. I. Sofronov (ORCID: https://orcid.org/0000-0001-9557-3685)
- K. M. Gadzhimuradova (ORCID: https://orcid.org/0000-0001-8101-1665)
- Peter A. Sparber (ORCID: https://orcid.org/0000-0002-9160-0794)
- Игорь Вячеславович Самойленко (ORCID: https://orcid.org/0000-0001-7150-5071)
- Гаджимурадов Марат Нурмагомедович (ORCID: https://orcid.org/0000-0002-3663-3235)
- Yа. V. Vishnevskaya (ORCID: https://orcid.org/0000-0002-4066-179X)
- Natalia N. Petenko (ORCID: https://orcid.org/0000-0002-5692-0223)
- Vera V. Semenova (ORCID: https://orcid.org/0000-0002-9705-1001)
- Irina S. Kletskaya (ORCID: https://orcid.org/0000-0002-8552-7682)
- Tatiana V. Nasedkina (ORCID: https://orcid.org/0000-0002-2642-4202)
- Svetlana N. Mikhailova (ORCID: https://orcid.org/0000-0001-6734-7832)
- Fatima Makhacheva (ORCID: https://orcid.org/0000-0003-3061-2668)
Publication Details
- Journal
- International Journal of Molecular Sciences
- Published
- 2026-11-04
- DOI
- https://doi.org/10.3390/ijms27219889
- Primary Topic
- DNA Repair Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 0.00