Comprehensive germline mutation analysis and clinical profile in a large cohort of Brazilian xeroderma pigmentosum patients.
J Eur Acad Dermatol Venereol
; 34(10): 2392-2401, 2020 Oct.
Article
in En
| MEDLINE
| ID: mdl-32239545
ABSTRACT
BACKGROUND:
Xeroderma pigmentosum (XP) patients present a high risk of developing skin cancer and other complications at an early age. This disease is characterized by mutations in the genes related to the DNA repair system.OBJECTIVES:
To describe the clinical and molecular findings in a cohort of 32 Brazilian individuals who received a clinical diagnosis of XP.METHODS:
Twenty-seven families were screened for germline variants in eight XP-related genes.RESULTS:
All patients (N = 32) were diagnosed with bi-allelic germline pathogenic or potentially pathogenic variants, including nine variants previously undescribed. The c.2251-1G>C XPC pathogenic variant, reported as the founder mutation in Comorian and Pakistani patients, was observed in 15 cases in homozygous or compound heterozygous. Seven homozygous patients for POLH/XPV variants developed their symptoms by an average age of 7.7 years. ERCC2/XPD, DDB2/XPE and ERCC5/XPG variants were found in a few patients. Aside from melanoma and non-melanoma skin tumours, a set of patients developed skin sebaceous carcinoma, leiomyosarcoma, angiosarcoma, mucoepidermoid carcinoma, gastric adenocarcinoma and serous ovarian carcinoma.CONCLUSIONS:
We reported a high frequency of XPC variants in 32 XP Brazilian patients. Nine new variants in XP-related genes, unexpected non-skin cancer lesions and an anticipation of the clinical manifestation in POLH/XPV cases were also described.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Xeroderma Pigmentosum
Type of study:
Risk_factors_studies
Limits:
Child
/
Humans
Country/Region as subject:
America do sul
/
Brasil
Language:
En
Journal:
J Eur Acad Dermatol Venereol
Journal subject:
DERMATOLOGIA
/
DOENCAS SEXUALMENTE TRANSMISSIVEIS
Year:
2020
Type:
Article
Affiliation country:
Brazil