Exome sequencing reveals a novel Fanconi group defined by XRCC2 mutation.
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.
Department of Genetics, King Faisal Specialist Hospital and Research Center, Saudi Arabia.
Hanan E
HE
Shamseldin
Mohamed
M
Elfaki
Fowzan S
FS
Alkuraya
D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics*; D001483:Base Sequence; D002675:Child, Preschool; D019457:Chromosome Breakage; D003241:Consanguinity; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D059472:Exome; D005199:Fanconi Anemia / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008297:Male
D004268:DNA-Binding Proteins; C113187:XRCC2 protein, human