2018 Fiscal Year Annual Research Report
Establishment of an integrated database of DNA repair deficiency disorders
| Project/Area Number |
17K17806
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| Research Institution | Nagoya University |
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Principal Investigator |
賈 楠 名古屋大学, 環境医学研究所, 特任助教 (90754060)
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Keywords | DDR-deficient disorders / Cockyane Syndrome / UV-sensitive syndrome |
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| Outline of Annual Research Achievements |
Cockayne syndrome (CS) is an autosomal recessive multisystem disorder with the diagnostic criteria including growth retardation, progressive neurological degeneration, photosensitivity, and et al. CS is associated with defect in transcription-coupled nucleotide excision repair (TC-NER), which removes UV photolesions specifically from actively transcribed genes. CS spans a clinical spectrum that includes type-I (CS-I, the classic form), type-II / COFS (Cerebro-Oculo-Facio-Skeletal) (CS-II, a more severe form), type-III (CS-III, a milder form), and type-IV (CS-IV, an adult-onset form). UV-sensitivity syndrome (UVSS) is another typical TC-NER associated disease, which only show mild freckles and photosensitivity. Most CS patients have defects in the ERCC8 (CSA) or ERCC6 (CSB) genes. Intriguingly, specific mutations in the CSA or CSB genes may also lead to UVSS. However, no clear genotype-phenotype relationships could be made so far.
We recently identified several Japanese very mild late onset CS- IV / UVSS cases with mutations in the CSB gene. Our research revealed distinct damage-response RNA polymerase II (RNAP II) processing in CS-I, CS-IV and UVSS patients, suggesting that milder phenotype in CS- IV / UVSS cases might be explained by faster degradation / removal of stalled RNAP II from damage sites. Our latest research on molecular analysis of CS and UVSS patients may gain insight into understanding the underlying mechanism of CS and UVSS.
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