DNA repair disorders

In order to provide the best possible care to patients with a rare condition, it is essential that global knowledge about the condition is gathered. Nationwide, centers of expertise have been set up to stimulate care for rare disorders and to gather knowledge. For the formal recognition of an expertise center by the Ministry of Health, an important condition is that the expertise center gathers, analyzes and shares knowledge through publications. These can be publications in scientific journals, but also treatment guidelines for health care professionals or information brochures for patients or caregivers. We optimize care and research within ENCORE through standardized follow-up and close collaboration between doctors and researchers. That way, we can ultimately develop better treatments for rare conditions. You may therefore be asked to participate in research. Participation in research is always on a voluntary basis. The data obtained is stored and analyzed in an anonymous form. All research has been approved in advance by an ethics review committee.

Genetic testing will be performed on all DNA repair disorders patients seen in our center of expertise to determine the genetic cause and to be able to support and advise the parents. If genetic testing has already been done elsewhere, it will not be repeated. This genetic knowledge also helps us to better understand the effect of the genetic change ("mutation") on the severity of symptoms. We can then also investigate which treatment works best for a particular mutation. In rare cases, the genetic analysis is inconclusive. In these cases, the genetic change will be further investigated in the laboratory.

Detailed knowledge about DNA repair disorders (which symptoms and complaints are there, and when exactly do they arise) is of great importance in order to recognize complaints early and treat them optimally. In addition, this is of great importance for drug research (trials). After all, only if we can demonstrate that a new drug improves the quality of life compared to an untreated patient, will the drug actually be approved and reimbursed. Because there are many differences between the DNA repair disorders, it is very important to gain insights into the course, the risks and the effects of (new) treatments. We will ask for your permission to include information about your child in our database.

In addition to permission to record these clinical data, you may be asked to provide a tube of blood for research. This blood is used to generate iPSC (induced Pluripotent Stem Cells) for research. Brain cells can be grown from these iPS cells. See the pre-clinical research page on this website for more information about iPS research.

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Ribeiro-Silva C. et. al. (2020) Ubiquitin and TFIIH-stimulated DDB2 dissociation drives DNA damage handover in nucleotide excision repair. Nat. Commun. 11:4868 Pubmed

Ragamin A, et al. (2020) Human RAD50 deficiency: Confirmation of a distinctive phenotype. Am J Med Genet A. 1-9 Pubmed

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Kuo M.E. & Theil A.F. et. al. (2019). Cysteinyl-tRNA Synthetase Mutations Cause a Multi-System, Recessive Disease That Includes Microcephaly, Developmental Delay, and Brittle Hair and Nails. Am J Hum Genet. pii: S0002-9297 Pubmed

Theil A.F. & Botta E. et. al. (2019) Bi-allelic TARS Mutations Are Associated with Brittle Hair Phenotype. Am J Hum Genet. 105:434-440 Pubmed

Menoni H & Wienholz F et. al. (2018) The transcription-coupled DNA repair-initiating protein CSB promotes XRCC1 recruitment to oxidative DNA damage.  Nucleic Acids Res. Pubmed

Ribeiro-Silva C. et. al. (2018). DNA damage sensitivity of SWI/SNF-deficient cells depends on TFIIH subunit p62/GTF2H1. Nat. Commun. 9:4067 Pubmed

Sabatella M. et. al. (2018). Repair protein persistence at DNA lesions characterizes XPF defect with Cockayne syndrome features. Nucleic Acids Res. 12;46(18):9563-9577. Pubmed

Theil A.F. et. al. (2017). Trichothiodystrophy causative TFIIEβ mutation affects transcription in highly differentiated tissue. Hum Mol Genet. Dec 1;26(23):4689-4698.  Pubmed

Vermeij W.P. et.al. (2016) Restricted diet delays accelerated ageing and genomic stress in DNA-repair-deficient mice. Nature. 537(7620), 427-31 Pubmed

Marteijn JA, Hoeijmakers JH, Vermeulen W (2015) Check, Check …Triple Check: Multi-Step DNA Lesion Identification by Nucleotide Excision Repair. Mol Cell 59:885-6 Pubmed

Tresini M. et al (2015). The core spliceosome as target and effector of non-canonical ATM signaling. Nature. 2;523(7558):53-8. Pubmed

Raj D.D. et.al. (2014) Priming of microglia in a DNA-repair deficient model of accelerated aging. Neurobiol. Aging. 35(9), 2147-60 Pubmed

Barnhoorn S, et.al. (2014) Cell-autonomous progeroid changes in conditional mouse models for repair endonuclease XPG deficiency. PLoS Genet. 10(10), e1004686 Pubmed

Jaarsma D, et.al. (2013) Cockayne syndrome pathogenesis: lessons from mouse models. Mech Ageing Dev. 134(5-6), 180-95 Pubmed

Jaarsma D, et.al. (2011) Age-related neuronal degeneration: complementary roles of nucleotide excision repair and transcription-coupled repair in preventing neuropathology. PLoS Genet. 7(12), e1002405 Pubmed

Borgesius N.Z. et.al. (2011) Accelerated age-related cognitive decline and neurodegeneration, caused by deficient DNA repair. J Neurosci. 31(35), 12543-53 Pubmed

De Waard M.C. et.al. (2010) Age-related motor neuron degeneration in DNA repair-deficient Ercc1 mice. Acta Neuropathol. 120(4), 461-75 Pubmed

Do you have questions about research at ENCORE? Or do you want to participate? Please contact us via encore@erasmusmc.nl or  DNArepair@erasmusmc.nl