KEGG   DISEASE: Disorders of nucleotide excision repairHelp
Entry
H00403                      Disease                                

Name
Disorders of nucleotide excision repair
  Subgroup
Xeroderma pigmentosum [DS:H01428]
Cockayne syndrome [DS:H00076]
UV-sensitive syndrome [DS:H02131]
Trichothiodystrophy [DS:H00866]
Cerebro-oculo-facio-skeletal syndrome
XFE progeroid syndrome
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, 7groups from the XP-A group to the G group show the abnormality in 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 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 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
Brite
Human diseases [BR:br08402]
 Congenital malformations
  Other congenital malformations
   H00403  Disorders of nucleotide excision repair
BRITE hierarchy
Pathway
hsa03420  Nucleotide excision repair
Gene
(XPA) XPA; xeroderma pigmentosum, complementation group A [HSA:7507] [KO:K10847]
(XPB, XP/CS, TTD) ERCC3; DNA excision repair protein ERCC-3 [HSA:2071] [KO:K10843]
(XPC) XPC; xeroderma pigmentosum, complementation group C [HSA:7508] [KO:K10838]
(XPD, XP/CS, TTD) ERCC2; DNA excision repair protein ERCC-2 [HSA:2068] [KO:K10844]
(XPE) DDB2; damage-specific DNA binding protein 2 [HSA:1643] [KO:K10140]
(XPE-2) DDB1; damage-specific DNA binding protein 1 [HSA:1642] [KO:K10610]
(XPF) ERCC4; DNA excision repair protein ERCC-4 [HSA:2072] [KO:K10848]
(XPG, XP/CS, COFS3) ERCC5; DNA excision repair protein ERCC-5 [HSA:2073] [KO:K10846]
(XPV) POLH; DNA polymerase eta [HSA:5429] [KO:K03509]
(CSA) ERCC8; DNA excision repair protein ERCC-8 [HSA:1161] [KO:K10570]
(CSB, DSC, UVS, COFS1) ERCC6; DNA excision repair protein ERCC-6 [HSA:2074] [KO:K10841]
(TTD) GTF2H5; general transcription factor IIH, polypeptide 5 [HSA:404672] [KO:K10845]
(COFS4) ERCC1; DNA excision repair protein ERCC-1 [HSA:2067] [KO:K10849]
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
  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
Reference
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
Reference
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
Reference
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
Reference
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
Reference
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

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