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

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Santiago, K. M. ^{[1, 2]} ; Castro, L. P. ^[3] ; Neto, J. P. D. ^[4] ; de Nobrega, A. F. ^{[1, 2]} ; Pinto, C. A. L. ^[5] ; Ashton-Prolla, P. ^{[6, 7]} ; Pinto e Vairo, F. ^{[8, 9]} ; de Medeiros, V, P. F. ; Ribeiro, E. M. ^[10] ; Ribeiro, B. F. R. ^[11] ; Valle, F. F. ^[12] ; Doriqui, M. J. R. ^[13] ; Leite, C. H. B. ^[14] ; Rocha, R. M. ^[15] ; Moura, L. M. S. ^[3] ; Munford, V ^[3] ; Galante, P. A. F. ^[16] ; Menck, C. F. M. ^[3] ; Rogatto, S. R. ^[17] ; Achatz, I, M.

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^[1] AC Camargo Canc Ctr, Dept Oncogenet, Sao Paulo, SP - Brazil

^[2] AC Camargo Canc Ctr, Int Res Ctr CIPE, Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Sao Paulo, SP - Brazil

^[4] AC Camargo Canc Ctr, Dept Skin Canc, Sao Paulo, SP - Brazil

^[5] AC Camargo Canc Ctr, Dept Pathol, Sao Paulo, SP - Brazil

^[6] Univ Fed Rio Grande do Sul, Dept Genet, Porto Alegre, RS - Brazil

^[7] Hosp Clin Porto Alegre, Med Genet Serv, Porto Alegre, RS - Brazil

^[8] Mayo Clin, Ctr Individualized Med, Rochester, MN - USA

^[9] Mayo Clin, Dept Clin Genom, Rochester, MN - USA

^[10] Assoc Cearense Doencas Genet, Fortaleza, Ceara - Brazil

^[11] Secretaria Estado Saude Acre, Childrens Hosp, Rio Branco, Acre - Brazil

^[12] Amazonas Fed Univ, Manaus, Amazonas - Brazil

^[13] Hosp Infantil Dr Juvencio Mattos, Sao Luis, Maranhao - Brazil

^[14] Inst Canc Ceara, Dept Radiat Oncol, Fortaleza, Ceara - Brazil

^[15] Fed Univ Sao Paulo UNIFESP, Paulista Med Sch, Gynecol Dept, Sao Paulo, SP - Brazil

^[16] Hosp Sirio Libanes, Mol Oncol Ctr, Sao Paulo, SP - Brazil

^[17] Univ Southern Denmark, Univ Hosp, Inst Reg Hlth Res, Dept Clin Genet, Vejle - Denmark

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY; v. 34, n. 10 MAY 2020.
• Citações Web of Science: 0

Resumo

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. (AU)

• Processo FAPESP: 09/16895-1 - Caracterização de mutações germinativas presentes nos genes XPA e XPC em pacientes brasileiros clinicamente diagnosticados com xeroderma Pigmentoso
• Beneficiário: Maria Isabel Alves de Souza Waddington Achatz
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/15982-6 - Consequências de deficiências de reparo de lesões no genoma
• Beneficiário: Carlos Frederico Martins Menck
• Modalidade de apoio: Auxílio à Pesquisa - Temático