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

Authors :
Castro, Ligia Pereira
Batista-Vieira, Danilo
de Souza, Tiago Antonio
Timoteo, Ana Rafaela de Souza
Coutinho, Jessica Dayanna Landivar
Pinheiro de Almeida, Isabel Cristina
Henriques, Sheila Ramos de Miranda
de Azevedo, Fabio Medeiros
Rosa, Reginaldo Cruz Alves
Kannouche, Patricia L
Sarasin, Alain
Menck, Carlos Frederico Martins
Petta, Tirzah Braz
Source :
Frontiers in Genetics
Publication Year :
2022
Publisher :
Frontiers Media S.A., 2022.

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.

Details

Language :
English
ISSN :
16648021
Volume :
12
Database :
OpenAIRE
Journal :
Frontiers in Genetics
Accession number :
edsair.pmid..........cea6ed31a452b6b955277c736f50378b