A novel nonsense mutation of ERCC2 in a Vietnamese family with xeroderma pigmentosum syndrome group D
| Autor: | Chi-Bao Bui, Thao Thi Phuong Duong, Vien The Tran, Thuy Thanh T. Pham, Tung Vu, Gia Cac Chau, Thanh-Niem Van Vo, Vinh Nguyen, Dieu-Thuong Thi Trinh, Minh Van Hoang |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities Xeroderma pigmentosum lcsh:QH426-470 Nonsense mutation lcsh:Life Genetic predisposition to disease Biology medicine.disease_cause Compound heterozygosity Biochemistry Article 030207 dermatology & venereal diseases 03 medical and health sciences 0302 clinical medicine Genetics research Genetics medicine Missense mutation Allele skin and connective tissue diseases Molecular Biology 030304 developmental biology 0303 health sciences Mutation integumentary system nutritional and metabolic diseases medicine.disease lcsh:Genetics lcsh:QH501-531 Transcription Factor TFIIH ERCC2 |
| Zdroj: | Human Genome Variation, Vol 7, Iss 1, Pp 1-8 (2020) Human Genome Variation |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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