21 July 2017


A gene mutation has been identified that links DNA repair defects and Fanconi anaemia, it has been announced.

So far, the disease has been linked with mutations in nearly 20 genes, all of which encode proteins involved in DNA repair mechanisms, which means that those with Fanconi anaemia have a higher risk of developing cancer because their DNA cannot be repaired.

The gene mutation was discovered by Professor Detlev Schindler, of the University of Wurzburg, Germany, and his colleagues made the discovery when examining Fanconi anaemia-like symptoms in a 12 year-old individual, who had no mutations in any known Fanconi anaemia genes.

When they sequenced the child’s individual's genome, they detected missense mutations in both alleles of the gene RFWD3, which encodes an enzyme that helps target other proteins for degradation.

Writing in the latest edition of the Journal of Clinical Investigation, Prof Schindler says the child’s cells were more sensitive to chromosome breakage and there were further indicators of increased susceptibility to DNA damage compared to cells from healthy individuals.

He said cells lacking RFWD3 or harbouring the patient's mutation showed similar DNA repair defects, which were rescued by expression of wild-type RFWD3.

RFWD3-deficient mice also exhibited a phenotype that resembled other mouse models of Fanconi anaemia.

Taken together, these findings support the identification of RFWD3 as a Fanconi anaemia gene, added Prof Schindler.

He said further studies of the enzyme could reveal its importance as a biomarker or therapeutic target in Fanconi anaemia, cancer, or other disease.

Source: Knies K, Inano S, Ramirez MJ et al. Biallelic mutations in the ubiquitin ligase RFWD3 cause Fanconi anaemia. J Clin Invest 10 July 2017; doi:10.1172/JCI92069.

Link: http://www.jci.org/articles/view/92069?key=85a36008596dbac1b621

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