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

Author(s):Show less -

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]}

Affiliation

^[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

• Document type: Journal article
• Source: FRONTIERS IN GENETICS; v. 12, JAN 17 2022.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 19/19435-3 - The role of DNA damage and mitochondrial function in vascular, immune and neurological ageing (DNA MoVINg)
• Grantee: Carlos Frederico Martins Menck
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center
• Grantee: Mayana Zatz
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC