You are here

Article Text

Article menu
Download PDFPDF
Review
DNA repair disorders
  1. C Geoffrey Woods
  1. Department of Clinical Genetics, Ashley Wing, St James’s University Hospital, Leeds LS9 7TF
  1. Dr Woods.

https://doi.org/10.1136/adc.78.2.178

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    Over the past 30 years a number of rare DNA repair disorder phenotypes have been delineated, for example Bloom’s syndrome, ataxia telangiectasia, and Fanconi’s anaemia. In each phenotype it was hypothesised that the underlying defect was an inability to repair a particular type of DNA damage. For some of these disorders this hypothesis was supported by cytogenetics studies using DNA damaging agents, these tests defined the so-called chromosome breakage syndromes. A number of the aetiological genes have recently been cloned, confirming that some DNA repair disorder phenotypes can be caused by more than one gene and vice versa. This review deals only with the more common DNA repair disorders. Rarer entities, such as Rothmund-Thomson syndrome and dyskeratosis congenita, are excluded. Some useful addresses are given at the end of the paper.

    Key messages

    • DNA repair disorders are caused by genes involved in DNA mutation detection, repair, or repair coordination. Many of the genes have other cellular functions, possibly explaining the diverse phenotypes seen in this group of disorders

    • The disorders are individually rare and suspected diagnoses should always confirmed by laboratory tests (which are reliable even before the full phenotype has evolved)

    • The disorders are autosomal recessive: prenatal diagnosis is available for most but may need to be arranged with specialist centres, before pregnancy

    • Many of the disorders are cancer prone but, as the individuals can be hypersensitive to chemotherapy and radiotherapy, treatment of any cancer that develops can be problematic

    DNA damage

    DNA is continually subjected to both exogenous and endogenous mutagenesis. Cells have built up sophisticated mechanisms to minimise the effects of this. Mutations in actively transcribed genes are preferentially repaired and all DNA should be repaired before DNA replication when a mutation can become “fixed” and be transmitted to daughter cells.

    Endogenous mutagenesis is the inevitable consequence of a …

    View Full Text