| H00403 | |
| H番号 | H00403 |
| 名称 | ヌクレオチド除去修復機構異常疾患 |
| 概要 | Mutations in genes on the nucleotide excision repair pathway are associated with diseases, such as xeroderma pigmentosum (XP), Cockayne syndrome (CS) and trichothiodystrophy (TTD). XP is caused by mutations in XPA, ERCC3/XPB, XPC, ERCC2/XPD, DDB2/XPE, ERCC4/XPF, ERCC5/XPG and POLH. XP is classified into eight genetic complementation groups by the present. In this inside, 7 groups from the XP-A group to the G group show the abnormality in nucleotide excision repair (NER). The symptoms of XP begin in early life. Severe sunburn and blistering occurs in a half of patients, and all show early extensive freckling. Cancer incidence for individuals with XP under 20 years of age is 2,000 times as high as incidence in the general population. Neurodegeneration can be correlated with mutations in specific XP genes (XPA, ERCC3, ERCC2 and ERCC5). Some patients of XP- A develop neurologic symptoms or a more severe clinical phenotype known as de Sanctis-Cacchione syndrome, associated with mutations in the ERCC6 gene. CS is caused by mutations in ERCC8/CSA, ERCC6/CSB. CS is predominantly a developmental and neurological disorder. It results in a severely reduced lifespan but is not linked to an increased incidence of cancer. The three of the XP genes (ERCC2, ERCC3, and ERCC5) are also found to be mutated in XP/CS patients (exhibiting both XP and Cockayne's symptoms). ERCC6 is a cause of UV-sensitive syndrome (UVS) which is characterized by photosensitivity and mild freckling but without neurological abnormalities or skin tumors. TTD is a premature aging syndrome, with the hallmark feature of brittle hair and nails, ichthyosis, and progressive mental and physical retardation. Within photo-sensitive TTD, three TFIIH coding genes (ERCC2, ERCC3, and TTDA/GTF2H5) are implicated. Cerebro-oculo-facio-skeletal (COFS) syndrome is a rare autosomal recessive disorder with microcephaly, severe mental retardation, and death in childhood. COFS can result from mutations in ERCC1, ERCC2, ERCC5 and ERCC6. |
| カテゴリ | 先天奇形 |
| ネットワーク | nt06502 Nucleotide excision repair |
| 病因遺伝子 | (XPA) XPA [HSA:7507] [KO:K10847] (XPB/CS, TTD) ERCC3 [HSA:2071] [KO:K10843] (XPC) XPC [HSA:7508] [KO:K10838] (XPD, TTD) ERCC2 [HSA:2068] [KO:K10844] (XPE) DDB2 [HSA:1643] [KO:K10140] (XPE-2) DDB1 [HSA:1642] [KO:K10610] (XPF/CS) ERCC4 [HSA:2072] [KO:K10848] (XPG/CS, COFS3) ERCC5 [HSA:2073] [KO:K10846] (XPV) POLH [HSA:5429] [KO:K03509] (CSA) ERCC8 [HSA:1161] [KO:K10570] (CSB, DSC, UVS, COFS1) ERCC6 [HSA:2074] [KO:K10841] (TTD) GTF2H5 [HSA:404672] [KO:K10845] (COFS4) ERCC1 [HSA:2067] [KO:K10849] |
| 病原体 | - |
| 環境要因 | - |
| 発癌物質 | - |
| 治療薬 | - |
| コメント | Disorder of DNA repair system |
| リンク | ICD-10: Q87 MeSH: D014983 D003057 C563466 D054463 OMIM: 278700 610651 278720 278730 278740 278760 278780 278750 216400 133540 278800 600630 601675 214150 610756 610758 610965 |
| 文献 | PMID:19809470 著者 Cleaver JE, Lam ET, Revet I タイトル Disorders of nucleotide excision repair: the genetic and molecular basis of heterogeneity. 雑誌 Nat Rev Genet 10:756-68 (2009) DOI:10.1038/nrg2663 PMID:11710928 (XP and TTD) 著者 Queille S, Drougard C, Sarasin A, Daya-Grosjean L タイトル Effects of XPD mutations on ultraviolet-induced apoptosis in relation to skin cancer-proneness in repair-deficient syndromes. 雑誌 J Invest Dermatol 117:1162-70 (2001) DOI:10.1046/j.0022-202x.2001.01533.x PMID:11443545 (COFS) 著者 Graham JM Jr, Anyane-Yeboa K, Raams A, Appeldoorn E, Kleijer WJ, Garritsen VH, Busch D, Edersheim TG, Jaspers NG タイトル Cerebro-oculo-facio-skeletal syndrome with a nucleotide excision-repair defect and a mutated XPD gene, with prenatal diagnosis in a triplet pregnancy. 雑誌 Am J Hum Genet 69:291-300 (2001) DOI:10.1086/321295 PMID:15220921 (TTD) 著者 Giglia-Mari G, Coin F, Ranish JA, Hoogstraten D, Theil A, Wijgers N, Jaspers NG, Raams A, Argentini M, van der Spek PJ, Botta E, Stefanini M, Egly JM, Aebersold R, Hoeijmakers JH, Vermeulen W タイトル A new, tenth subunit of TFIIH is responsible for the DNA repair syndrome trichothiodystrophy group A. 雑誌 Nat Genet 36:714-9 (2004) DOI:10.1038/ng1387 PMID:18339586 (TTD and CS) 著者 Brooks PJ, Cheng TF, Cooper L タイトル Do all of the neurologic diseases in patients with DNA repair gene mutations result from the accumulation of DNA damage? 雑誌 DNA Repair (Amst) 7:834-48 (2008) DOI:10.1016/j.dnarep.2008.01.017 PMID:20221251 (XFE progeroid syndrome) 著者 Ahmad A, Enzlin JH, Bhagwat NR, Wijgers N, Raams A, Appledoorn E, Theil AF, J Hoeijmakers JH, Vermeulen W, J Jaspers NG, Scharer OD, Niedernhofer LJ タイトル Mislocalization of XPF-ERCC1 nuclease contributes to reduced DNA repair in XP-F patients. 雑誌 PLoS Genet 6:e1000871 (2010) DOI:10.1371/journal.pgen.1000871 |