PC and POLH/XPV Genes Mutated in a Genetic Cluster of Xeroderma Pigmentosum Patients in Northeast Brazi

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Castro, Ligia Pereira ^[1] ; Batista-Vieira, Danilo ^[1] ; de Souza, Tiago Antonio ^[1] ; Timoteo, Ana Rafaela de Souza ^[2] ; Coutinho, Jessica Dayanna Landivar ^[2] ; Pinheiro de Almeida, Isabel Cristina ^[3] ; Henriques, Sheila Ramos de Miranda ^[3] ; Azevedo, Fabio Medeiros de ^[3] ; Rosa, Reginaldo Cruz Alves ^{[4, 5]} ; Kannouche, Patricia L. ^[5] ; Sarasin, Alain ^[5] ; Menck, Carlos Frederico Martins ^[1] ; Petta, Tirzah Braz ^{[2, 3, 6, 7]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, DNA Repair Lab, Sao Paulo, SP - Brazil

^[2] Univ Fed Rio Grande do Norte, Dept Cell Biol & Genet, Natal, RN - Brazil

^[3] CECAN, Inst Ensino Pesquisa & Inovacao, Liga Canc, Natal, RN - Brazil

^[4] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Genet, Ribeirao Preto - Brazil

^[5] Univ Paris Saclay, Gustave Roussy, CNRS, UMR9019, Genome Integr & Cancers, Paris - France

^[6] USC Keck Sch Med, Dept Pathol, Hoffman Med Res Bldg, Los Angeles, CA - USA

^[7] Karolinska Inst Radiumhemmet, Karolinska Univ Hosp Solna, Clin Pathol & Cytol, Stockholm - Sweden

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN GENETICS; v. 12, JAN 17 2022.
• Citações Web of Science: 0

Resumo

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. (AU)

• Processo FAPESP: 19/19435-3 - Papel de danos no DNA e função mitocondrial em envelhecimento vascular, imune e neurológico (DNA MoVINg)
• Beneficiário: Carlos Frederico Martins Menck
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 13/08028-1 - CEGH-CEL - Centro de Estudos do Genoma Humano e de Células-Tronco
• Beneficiário: Mayana Zatz
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs