Comprehensive germline mutation analysis and clinical profile in a large cohort of Brazilian xeroderma pigmentosum patients

K. M. Santiago, L. P. Castro, J. P.D. Neto, A. F. de Nóbrega, C. A.L. Pinto, P. Ashton-Prolla, F. Pinto e Vairo, P. F.V. de Medeiros, E. M. Ribeiro, B. F.R. Ribeiro, F. F. do Valle, M. J.R. Doriqui, C. H.B. Leite, R. M. Rocha, L. M.S. Moura, V. Munford, P. A.F. Galante, C. F.M. Menck, S. R. Rogatto, M. I. Achatz

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Background: Xeroderma pigmentosum (XP) patients present a high risk of developing skin cancer and other complications at an early age. This disease is characterized by mutations in the genes related to the DNA repair system. Objectives: To describe the clinical and molecular findings in a cohort of 32 Brazilian individuals who received a clinical diagnosis of XP. Methods: Twenty-seven families were screened for germline variants in eight XP-related genes. Results: All patients (N = 32) were diagnosed with bi-allelic germline pathogenic or potentially pathogenic variants, including nine variants previously undescribed. The c.2251-1G>C XPC pathogenic variant, reported as the founder mutation in Comorian and Pakistani patients, was observed in 15 cases in homozygous or compound heterozygous. Seven homozygous patients for POLH/XPV variants developed their symptoms by an average age of 7.7 years. ERCC2/XPD, DDB2/XPE and ERCC5/XPG variants were found in a few patients. Aside from melanoma and non-melanoma skin tumours, a set of patients developed skin sebaceous carcinoma, leiomyosarcoma, angiosarcoma, mucoepidermoid carcinoma, gastric adenocarcinoma and serous ovarian carcinoma. Conclusions: We reported a high frequency of XPC variants in 32 XP Brazilian patients. Nine new variants in XP-related genes, unexpected non-skin cancer lesions and an anticipation of the clinical manifestation in POLH/XPV cases were also described.

Original languageEnglish (US)
Pages (from-to)2392-2401
Number of pages10
JournalJournal of the European Academy of Dermatology and Venereology
Issue number10
StatePublished - Oct 1 2020

ASJC Scopus subject areas

  • Dermatology
  • Infectious Diseases


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