Abstract: 【Abstract】 Objective To detect gene mutations in two patients with xeroderma pigmentosum （XP）. Methods Clinical data were collected from two patients with XP. DNA was extracted from peripheral blood of the patients and their parents, and high-throughput whole-exome sequencing was performed in the patient to identify pathogenic gene mutations. Then, Sanger sequencing was performed to bidirectionally verify the mutations in the patients and their parents, with a focus on mutations in the candidate genes XPA, ERCC3, XPC, ERCC2, DDB2, ERCC4, ERCC5 and POLH. Results Case 1, a 3-year-old male patient, presented with brown spots and hypopigmented macules on the face, ears, neck and back of both hands for 2 years, as well as gait instability for 1 year. The skin lesions were mainly distributed in sun-exposed areas and worsened in summer. Case 2, a male patient aged 1 year and 5 months, presented with scattered brown spots and a few hypopigmented macules on the face for 1 year. Genetic testing showed compound heterozygous mutations in the ERCC2 gene of case 1, including c.1805G>A （p.Gly602Asp） mutation inherited from his father and c.586C>T （p.Arg196Ter） mutation inherited from the his mother, so case 1 was diagnosed with XP group D （XPD）. Compound heterozygous mutations were identified in the ERCC5 gene of case 2, including c.2533+2T>C mutation inherited from his father and c.2453C>T（p.Ala818Val）mutation inherited from his mother, so case 2 was diagnosed with XP group G （XPG）. The c.586C>T（p.Arg196Ter）and c.2533+2T>C mutations had not been reported before. Sun protection was suggested. After a follow-up of 2 years, skin lesions increased in the 2 patients, but no malignant tumors occurred. Conclusions The compound heterozygous mutations in the ERCC2 gene can lead to XPD, mainly manifesting as cutaneous and neurological symptoms, while the compound heterozygous mutations in the ERCC5 gene can lead to XPG, manifesting as a mild phenotype. Early clinical features combined with genetic testing are helpful for accurate diagnosis and classification of XP.

Key words: Xeroderma pigmentosum, DNA mutational analysis, Skin manifestations, ERCC2 gene, ERCC5 gene