Xeroderma pigmentosum: low prevalence of germline XPA mutations in a Brazilian XP population.

Karina Santiago,Silvia Rogatto,Amanda França De Nóbrega,Rafael Rocha,Maria Achatz

doi:10.3390/ijms16048988

Karina Santiago, Silvia Rogatto + Show 3 more

Open Access

https://doi.org/10.3390/ijms16048988

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Abstract

Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder characterized by DNA repair defects that cause photophobia, sunlight-induced cancers, and neurodegeneration. Prevalence of germline mutations in the nucleotide excision repair gene XPA vary significantly in different populations. No Brazilian patients have been reported to carry a germline mutation in this gene. In this study, the germline mutational status of XPA was determined in Brazilian patients exhibiting major clinical features of XP syndrome. The study was conducted on 27 unrelated patients from select Brazilian families. A biallelic inactivating transition mutation c.619C>T (p.Arg207Ter) was identified in only one patient with a history of neurological impairment and mild skin abnormalities. These findings suggest that XP syndrome is rarely associated with inherited disease-causing XPA mutations in the Brazilian population. Additionally, this report demonstrates the effectiveness of genotype-phenotype correlation as a valuable tool to guide direct genetic screening.

Highlights

Xeroderma pigmentosum (XP) is a rare autosomal recessive syndrome associated with mutations in one of the seven genes involved in Nucleotide Excision Repair pathway of damaged DNA
The findings suggest that XP syndrome is rarely associated with XPA mutations in the Brazilian population
Twenty-seven unrelated patients who fulfilled the main criteria for XP syndrome were evaluated for germline XPA mutations

Summary

Introduction

Xeroderma pigmentosum (XP) is a rare autosomal recessive syndrome associated with mutations in one of the seven genes involved in Nucleotide Excision Repair pathway of damaged DNA. XP patients have a 10,000-fold increased risk of developing non-melanoma skin cancer before the age of 10 and a 2000-fold increase in the incidence of malignant melanoma before the age of 20 compared to the general population. The prevalence of germline XPA mutations in XP patients varies, accounting for 55% of all Japanese. A few studies involving a small number of Brazilian XP cases have been published; to the best of our knowledge, the frequency of germline XPA mutations in this population has not yet been described [10,11,12,13], thereby hindering the evaluation of genotype-phenotype correlations. The main purpose of this study was to screen germline XPA pathogenic alterations in a group of Brazilian patients clinically diagnosed with XP syndrome. The findings suggest that XP syndrome is rarely associated with XPA mutations in the Brazilian population

Germline Mutation Spectrum of XP Syndrome and Clinical Profile

Case Report

Enrollment of Patients and Ethics Statement

Genomic DNA Extraction

XPA Direct Sequencing

XPA Protein Expression by Immunohistochemistry