A novel nonsense mutation of ERCC2 in a Vietnamese family with xeroderma pigmentosum syndrome group D

• Published in: Human genome variation 2020, Vol.7 (1), p.2-2, Article 2
• Main Authors: Bui, Chi-Bao, Duong, Thao Thi Phuong, Tran, Vien The, Pham, Thuy Thanh T., Vu, Tung, Chau, Gia Cac, Vo, Thanh-Niem Van, Nguyen, Vinh, Trinh, Dieu-Thuong Thi, Hoang, Minh Van
• Format: Article
• Language: English
• Subjects: 631/208/727/2000; 692/308/2056; Biomedical and Life Sciences; Biomedicine; Deoxyribonucleic acid; DNA; DNA damage; Gene Expression; Gene Function; Gene Therapy; Genomes; Human Genetics; Molecular Medicine; Mutation; Patients; Transcription factors
• ISSN: 2054-345X; 2054-345X
• DOI: 10.1038/s41439-020-0089-z

Xeroderma pigmentosum (XP) group D, a severe disease often typified by extreme sun sensitivity, can be caused by ERCC2 mutations. ERCC2 encodes an adenosine triphosphate (ATP)-dependent DNA helicase, namely XP group D protein (XPD). The XPD, one of ten subunits of the transcription factor TFIIH, plays a critical role in the nucleotide-excision repair (NER) pathway. Mutations in XPD that affect the NER pathway can lead to neurological degeneration and skin cancer, which are the most common causes of death in XP patients. Here, we present detailed phenotypic information on a Vietnamese family in which four members were affected by XP with extreme sun sensitivity. Genomic analysis revealed a compound heterozygous mutation of ERCC2 that affected family members and single heterozygous mutations in unaffected family members. We identified a novel, nonsense mutation in one allele of ERCC2 (c.1354C > T, p.Q452X) and a known missense mutation in the other allele (c.2048G > A, p.R683Q). Fibroblasts isolated from the compound heterozygous subject also failed to recover from UV-driven DNA damage, thus recapitulating aspects of XP syndrome in vitro. We describe a novel ERCC2 variant that leads to the breakdown of the NER pathway across generations of a family presenting with severe XP. Xeroderma pigmentosum: New mutation linked to sun-sensitivity disorder A novel mutation in a gene responsible for repairing DNA helps explain why members of one Vietnamese family suffer from heightened sensitivity to ultraviolet rays from sunlight. A team led by Minh Van Hoang from the University Medical Center, Ho Chi Minh City, Vietnam, sequenced the protein-coding portions of the genomes from one brother and two sisters affected by xeroderma pigmentosum, an inherited disorder characterized by extreme sun sensitivity in the skin and eyes. The researchers found that all three siblings carried two different mutations, one in each copy of a DNA-repair gene called ERCC2 . One mutation had previously been implicated in many cases of xeroderma pigmentosum, but the other had never been reported before. These findings could aid in the diagnosis, prevention and treatment of this rare hereditary condition.