Spectrum and significance of variants and mutations in the Fanconi anaemia group G gene in children with sporadic acute myeloid leukaemia

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Abstract
Childhood acute myeloid leukaemia (AML) is uncommon. Children with Fanconi anaemia (FA), however, have a very high risk of developing AML. FA is a rare inherited disease caused by mutations in at least 12 genes, of which Fanconi anaemia group G gene (FANCG) is one of the commonest. To address to what extent FANCG variants contribute to sporadic childhood AML, we determined the spectrum of FANCG sequence variants in 107 children diagnosed with sporadic AML, using polymerase chain reaction (PCR), fluorescent single‐strand conformational polymorphism (SSCP) and sequencing methodologies. The significance of variants was determined by frequency analysis and assessment of evolutionary conservation. Seven children (6·5%) carried variants in FANCG. Two of these carried two variants, including the known IVS2 + 1G>A mutation with the novel missense mutation S588F, and R513Q with the intronic deletion IVS12‐38 (‐28)_del11, implying that these patients might have been undiagnosed FA patients. R513Q, which affects a semi‐conserved amino acid, was carried in two additional children with AML. Although not significant, the frequency of R513Q was higher in children with AML than unselected cord bloods. While FANCG mutation carrier status does not predispose to sporadic AML, the identification of unrecognised FA patients implies that FA presenting with primary AML in childhood is more common than suspected.