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A novel missense variant and multiexon deletion causing a delayed presentation of xeroderma pigmentosum, group C.

Authors :
Macke EL
Morales-Rosado JA
Gupta A
Schmitz CT
Kruisselbrink T
Lanpher B
Klee EW
Source :
Cold Spring Harbor molecular case studies [Cold Spring Harb Mol Case Stud] 2020 Aug 25; Vol. 6 (4). Date of Electronic Publication: 2020 Aug 25 (Print Publication: 2020).
Publication Year :
2020

Abstract

Pathogenic variants in the XPC complex subunit, DNA damage recognition, and repair factor ( XPC ) are the cause of xeroderma pigmentosum, group C (MIM: 278720). Xeroderma pigmentosum is an inherited condition characterized by hypersensitivity to ultraviolet (UV) irradiation and increased risk of skin cancer due to a defect in nucleotide excision repair (NER). Here we describe an individual with a novel missense variant and deletion of exons 14-15 in XPC presenting with a history of recurrent melanomas. The proband is a 39-yr-old female evaluated through the Mayo Clinic Department of Clinical Genomics. Prior to age 36, she had more than 60 skin biopsies that showed dysplastic nevi, many of which had atypia. At age 36 she presented with her first melanoma in situ, and since then has had more than 10 melanomas. The proband underwent research whole-exome sequencing (WES) through the Mayo Clinic's Center for Individualized Medicine and a novel heterozygous variant of uncertain significance (VUS) in XPC (c.1709T > G, p.Val570Gly) was identified. Clinical confirmation pursued via XPC gene sequencing and deletion/duplication analysis of XPC revealed a pathogenic heterozygous deletion of ∼1 kb within XPC , including exons 14 and 15. Research studies determined the alterations to be in trans Although variants in XPC generally result in early-onset skin cancer in childhood, the proband is atypical in that she did not present with her first melanoma until age 36. Review of the patient's clinical, pathological, and genetic findings points to a diagnosis of delayed presentation of xeroderma pigmentosum.<br /> (© 2020 Macke et al.; Published by Cold Spring Harbor Laboratory Press.)

Details

Language :
English
ISSN :
2373-2873
Volume :
6
Issue :
4
Database :
MEDLINE
Journal :
Cold Spring Harbor molecular case studies
Publication Type :
Academic Journal
Accession number :
32843428
Full Text :
https://doi.org/10.1101/mcs.a005165