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.
Human diseases [BR:br08402]
Other congenital malformations
H00403 Disorders of nucleotide excision repair