XPC and POLH/XPV Genes Mutated in a Genetic Cluster of Xeroderma Pigmentosum Patients in Northeast Brazil.

Autor:	Castro LP; DNA Repair Laboratory, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil., Batista-Vieira D; DNA Repair Laboratory, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil., de Souza TA; DNA Repair Laboratory, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil., Timoteo ARS; Department of Cell Biology and Genetics Federal University of Rio Grande do Norte, Natal, Brazil., Coutinho JDL; Department of Cell Biology and Genetics Federal University of Rio Grande do Norte, Natal, Brazil., Pinheiro de Almeida IC; Instituto de Ensino, Pesquisa e Inovação, Liga Contra o Câncer, CECAN, Natal, Brazil., Henriques SRM; Instituto de Ensino, Pesquisa e Inovação, Liga Contra o Câncer, CECAN, Natal, Brazil., de Azevedo FM; Instituto de Ensino, Pesquisa e Inovação, Liga Contra o Câncer, CECAN, Natal, Brazil., Rosa RCA; Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.; UMR9019 - CNRS, Genome Integrity and Cancers, Université Paris-Saclay, Gustave Roussy, France., Kannouche PL; UMR9019 - CNRS, Genome Integrity and Cancers, Université Paris-Saclay, Gustave Roussy, France., Sarasin A; UMR9019 - CNRS, Genome Integrity and Cancers, Université Paris-Saclay, Gustave Roussy, France., Menck CFM; DNA Repair Laboratory, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil., Petta TB; Department of Cell Biology and Genetics Federal University of Rio Grande do Norte, Natal, Brazil.; Instituto de Ensino, Pesquisa e Inovação, Liga Contra o Câncer, CECAN, Natal, Brazil.; Department of Pathology, Hoffman Medical Research Building, USC Keck School of Medicine, Los Angeles, CA, United States.; Clinical Pathology and Cytology, Karolinska Institute Radiumhemmet, Karolinska University Hospital in Solna, Stockholm, Sweden.
Jazyk:	angličtina
Zdroj:	Frontiers in genetics [Front Genet] 2022 Jan 17; Vol. 12, pp. 784963. Date of Electronic Publication: 2022 Jan 17 (Print Publication: 2021).
DOI:	10.3389/fgene.2021.784963
Abstrakt:	Xeroderma pigmentosum (XP) is a rare genetic condition in which exposure to sunlight leads to a high tumor incidence due to defective DNA repair machinery. Herein, we investigated seven patients clinically diagnosed with XP living in a small city, Montanhas (Rio Grande do Norte), in the Northeast region of Brazil. We performed high-throughput sequencing and, surprisingly, identified two different mutated genes. Six patients carry a novel homozygote mutation in the POLH/XPV gene, c.672_673insT (p.Leu225Serfs*33), while one patient carries a homozygote mutation in the XPC gene, c.2251-1G>C. This latter mutation was previously described in Southeastern Africa (Comoro Island and Mozambique), Pakistan, and in a high incidence in Brazil. The XP-C patient had the first symptoms before the first year of life with aggressive ophthalmologic tumor progression and a melanoma onset at 7 years of age. The XP-V patients presented a milder phenotype with later onset of the disorder (mean age of 16 years old), and one of the six XP-V patients developed melanoma at 72 years. The photoprotection is minimal among them, mainly for the XP-V patients. The differences in the disease severity between XP-C (more aggressive) and XP-V (milder) patients are obvious and point to the major role of photoprotection in the XPs. We estimate that the incidence of XP patients at Montanhas can be higher, but with no diagnosis, due to poor health assistance. Patients still suffer from the stigmatization of the condition, impairing diagnosis, education for sun protection, and medical care. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Castro, Batista-Vieira, de Souza, Timoteo, Coutinho, Pinheiro de Almeida, Henriques, Azevedo, Rosa, Kannouche, Sarasin, Menck and Petta.)
Databáze:	MEDLINE
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