Clinical and molecular characterization of Xeroderma pigmentosum in Moroccan population: a case series of 40 patients

Abstract

Abstract Background Xeroderma pigmentosum (XP) is a rare autosomal recessive skin disorder characterized by hyperpigmentation, premature skin aging, ocular and cutaneous photosensitivity with increased risk of skin tumors. XP is caused by mutations in DNA repair genes that protect cells from UV-induced DNA damage. The current study aims to investigate, on clinical and genetic basis, Moroccan XP patients. We explored by direct sequencing the involvement of the prevalent XPA and XPC genes mutations: nonsense mutation (c.682C>T, p.Arg228X) and a two-base-pair (2 bp) deletion (c.1643 1644delTG or p.Val548Ala fsX25), respectively, in 40 index cases from 37 unrelated families in Moroccan population. Results Early skin and ocular manifestations were detected with high rate of malignancy. Cutaneous lesions progressed to malignant skin tumor in 70% of cases. Ocular tumors were also observed in 11 patients including BCC in eight cases, SCC in three cases and melanoma in four cases. Among the 40 patients, there were 20 homozygous cases for the 2 bp deletion in the XPC gene and 9 homozygous cases carrying the nonsense XPA mutation. Conclusion These findings obtained in the present study revealed that the XPC gene mutation (c.1643 1644delTG, p.Val548AlafsX25) is the major cause of Xeroderma pigmentosum in our population. The c.682C>T (p.Arg228X) mutation is relatively associated with moderate phenotype in XP group A Moroccan families. This result will also contribute to improving the molecular diagnosis of XP disease and will have a significant impact on improving the care of Moroccan patients and their relatives.

Keywords

• Xeroderma pigmentosum
• Rare autosomal recessive
• XPC
• XPA
• Tumor
• Mutation