| H00403 | |
| H number | H00403 |
| Name | Disorders of nucleotide excision repair |
| Description | 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. |
| Category | Congenital malformation |
| Network | nt06502 Nucleotide excision repair |
| Gene | (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] |
| Pathogen | - |
| Env factor | - |
| Carcinogen | - |
| Drug | - |
| Comment | Disorder of DNA repair system |
| Other DBs | 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 |
| Reference | PMID:19809470 AUTHORS Cleaver JE, Lam ET, Revet I TITLE Disorders of nucleotide excision repair: the genetic and molecular basis of heterogeneity. JOURNAL Nat Rev Genet 10:756-68 (2009) DOI:10.1038/nrg2663 PMID:11710928 (XP and TTD) AUTHORS Queille S, Drougard C, Sarasin A, Daya-Grosjean L TITLE Effects of XPD mutations on ultraviolet-induced apoptosis in relation to skin cancer-proneness in repair-deficient syndromes. JOURNAL J Invest Dermatol 117:1162-70 (2001) DOI:10.1046/j.0022-202x.2001.01533.x PMID:11443545 (COFS) AUTHORS Graham JM Jr, Anyane-Yeboa K, Raams A, Appeldoorn E, Kleijer WJ, Garritsen VH, Busch D, Edersheim TG, Jaspers NG TITLE Cerebro-oculo-facio-skeletal syndrome with a nucleotide excision-repair defect and a mutated XPD gene, with prenatal diagnosis in a triplet pregnancy. JOURNAL Am J Hum Genet 69:291-300 (2001) DOI:10.1086/321295 PMID:15220921 (TTD) AUTHORS 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 TITLE A new, tenth subunit of TFIIH is responsible for the DNA repair syndrome trichothiodystrophy group A. JOURNAL Nat Genet 36:714-9 (2004) DOI:10.1038/ng1387 PMID:18339586 (TTD and CS) AUTHORS Brooks PJ, Cheng TF, Cooper L TITLE Do all of the neurologic diseases in patients with DNA repair gene mutations result from the accumulation of DNA damage? JOURNAL DNA Repair (Amst) 7:834-48 (2008) DOI:10.1016/j.dnarep.2008.01.017 PMID:20221251 (XFE progeroid syndrome) AUTHORS 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 TITLE Mislocalization of XPF-ERCC1 nuclease contributes to reduced DNA repair in XP-F patients. JOURNAL PLoS Genet 6:e1000871 (2010) DOI:10.1371/journal.pgen.1000871 |