A novel mutation in XPC genee causing xeroderma pigmentosum complementation group C

Background and Aim: Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder that first was described by Hebra and Kaposi in ۱۸۷۴. It affects about ۱ in ۲۵۰,۰۰۰ people in the United States and ۱ in ۴۳۰,۰۰۰ in Europe. The condition condition is more common in Japan, North Africa, and the Middle East. It is a genetically and clinically heterogeneous disease characterized by photosensitivity, pigmentary changes, premature skin aging, and malignant tumor development. These symptoms are due to a cellular hypersensitivity to ultraviolet radiation caused by a defect in DNA repair. Many of the genes related to XP are parts of a DNA-repair process that is commonly known as nucleotide excision repair (NER). Depending on the affected gene, eight complementation groups have been described for XP: classical XP (XPA to XPG) with defective NER and XP variant (XPV) with normal NER.Methods: In this study, a ۳-year-old Iranian boy diagnosed with xeroderma pigmentosum group C was described. He presented with symptoms of dry skin (xeroderma), changes in skin coloring (pigmentation) and sunburn after exposure to sunlight. Since XP is a genetically and clinically heterogeneous disease for genetic analysis, genomic DNA was extracted from whole blood and whole exome sequencing (WES) was performed. The obtained results were verified by Sanger sequencing.Results: Patient manifested the typical clinical feature of XP. Interpretation of the WES data revealed a pathogenic frameshift homozygous mutation (c.۱۴۴۰_۱۴۴۱insTCAGAGGACAAAGGAGGCAC, p.Lys۴۸۱fs) in XPC gene. This variant was not previously reported. This variant was located at conserved sequence according to the GERP database and protein modeling was performed on the variant to better characterize its clinical signi?cance and to con?rm its pathogenicity.Conclusion: This study identified a new pathogenic XPC variant in the patient that matched his clinical phenotype, including sun sensitivity, dry and pigmented skin without neurological abnormalities (such as delayed development and hearing loss). This phenotype is consistent with the XP group C characteristics resulted from XPC gene mutations. The results of this study contributes to further identification of the mutation spectrum of XP in consanguineous Iranian families and can help in prenatal diagnosis of the disease.