@article{de2cd1f1f7fd43279565f889e7899561,
title = "Comprehensive germline mutation analysis and clinical profile in a large cohort of Brazilian xeroderma pigmentosum patients",
abstract = "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.",
author = "Santiago, {K. M.} and Castro, {L. P.} and Neto, {J. P.D.} and {de N{\'o}brega}, {A. F.} and Pinto, {C. A.L.} and P. Ashton-Prolla and {Pinto e Vairo}, F. and {de Medeiros}, {P. F.V.} and Ribeiro, {E. M.} and Ribeiro, {B. F.R.} and {do Valle}, {F. F.} and Doriqui, {M. J.R.} and Leite, {C. H.B.} and Rocha, {R. M.} and Moura, {L. M.S.} and V. Munford and Galante, {P. A.F.} and Menck, {C. F.M.} and Rogatto, {S. R.} and Achatz, {M. I.}",
note = "Funding Information: The patients in this manuscript have given written informed consent to publication of their case details. We thank the XP families for supporting the research, making samples and medical records available. We acknowledge the support of Dr Eduard Ren{\'e} Brechtb{\"u}hl and Dr Marco Antonio de Oliveira, from the Department of Cutaneous Oncology, A.C.Camargo Cancer Center (S{\~a}o Paulo, Brazil), for referring their XP patients. We are grateful to the Oncogenetic Department (genetic counselling), A.C.Camargo Cancer Center Biobank (DNA samples) and the Anatomic Pathology Department (Ivan Carlos Dias Lacerda, Lais Takata Walter, and Rafaela Batista da Cruz) (immunohistochemistry assay) at A.C.Camargo Cancer Center, S{\~a}o Paulo, Brazil. We thank the Core Facility for Scientific Research – University of Sao Paulo – CEFAP-USP/GENIAL (Genome Investigation and Analysis Laboratory) for the target-next-generation sequencing analysis. Funding Information: The patients in this manuscript have given written informed consent to publication of their case details. We thank the XP families for supporting the research, making samples and medical records available. We acknowledge the support of Dr Eduard Ren{\'e} Brechtb{\"u}hl and Dr Marco Antonio de Oliveira, from the Department of Cutaneous Oncology, A.C.Camargo Cancer Center (S{\~a}o Paulo, Brazil), for referring their XP patients. We are grateful to the Oncogenetic Department (genetic counselling), A.C.Camargo Cancer Center Biobank (DNA samples) and the Anatomic Pathology Department (Ivan Carlos Dias Lacerda, Lais Takata Walter, and Rafaela Batista da Cruz) (immunohistochemistry assay) at A.C.Camargo Cancer Center, S{\~a}o Paulo, Brazil. We thank the Core Facility for Scientific Research – University of Sao Paulo – CEFAP‐USP/GENIAL (Genome Investigation and Analysis Laboratory) for the target‐next‐generation sequencing analysis. Publisher Copyright: {\textcopyright} 2020 European Academy of Dermatology and Venereology",
year = "2020",
month = oct,
day = "1",
doi = "10.1111/jdv.16405",
language = "English (US)",
volume = "34",
pages = "2392--2401",
journal = "Journal of the European Academy of Dermatology and Venereology",
issn = "0926-9959",
publisher = "Wiley-Blackwell",
number = "10",
}