Abstract
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. To describe the clinical and molecular findings in a cohort of 32 Brazilian individuals who received a clinical diagnosis of XP. Twenty-seven families were screened for germline variants in eight XP-related genes. 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 7.7years. 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. 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.
Highlights
Xeroderma pigmentosum (XP) is a rare autosomal recessive disease characterized by photosensitivity due to DNA damage mostly in response to ultraviolet (UV) radiation exposure
ERCC2/XPD, DDB2/XPE, and ERCC5/XPG variants were found in a few patients
We reported a high frequency of XPC variants in 32 XP Brazilian patients
Summary
Xeroderma pigmentosum (XP) is a rare autosomal recessive disease characterized by photosensitivity due to DNA damage mostly in response to ultraviolet (UV) radiation exposure. Classical XP patients harbor bi-allelic germline pathogenic variants in genes (XPA, ERCC3/XPB, XPC, ERCC2/XPD, DDB2/XPE, ERCC4/XPF, and ERCC5/XPG) that encode proteins of the Nucleotide Excision Repair pathway. A variant form of the disease is characterized by an inefficiency in bypassing DNA damage during replication (translesion synthesis). This inability occurs due to bi-allelic pathogenic variants in POLH/XPV that encode a translesion synthesis DNA polymerase[4,5]. 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
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Journal of the European Academy of Dermatology and Venereology
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
