Abstract
Background Fanconi anaemia (FA) is a group of disorders characterised by progressive bone marrow failure and a characteristic but variable craniofacial and skeletal involvement. Recessive mutations in any of 15 genes linked to FA lead to the pathognomonic increased susceptibility to double-strand DNA breaks.
Methods Autozygome and exome analysis of a patient with classic FA phenotype
Results The authors identified a novel truncating mutation in XRCC2. Consistent with the proposed causal link to FA, this gene is an essential non-redundant component of the RAD51 family of homologous repair proteins and its deficiency in a murine model has been shown to lead to a highly similar phenotype to that of this patient both at the cellular and organismal level.
Conclusion This study implicates XRCC2 in the pathogenesis of FA and calls for further investigation of the potential contribution of XRCC2 mutations to the overall mutational load of FA.