FANCG 637-643 deletion mutation: frequency in black patients with acute myeloid leukaemia or aplastic anaemia and the clinical phenotype of homozygotes

[摘要] Fanconi anaemia (FA) is an autosomal recessive disorder characterised by aplastic anaemia(AA) and a high risk of developing acute myeloid leukaemia (AML). It is unknownwhether heterozygote carriers are also predisposed to developing these disorders.The black South African population group is ideal for FA mutation screening because thepresence of a founder mutation, FANCG 637-643, makes screening relatively straightforward. Three individuals with AML (115 screened) and one with AA (78 screened) werefound to be heterozygous for the black South African founder mutation. From our data itseems unlikely that this mutation places heterozygous carriers of the mutation at high riskof developing AML or AA. Three children with AA out of 26 screened, were homozygousfor the mutation. This finding reiterates the importance of screening all children with AAfor FA.The frequency of certain congenital abnormalities in black South African FA patients wascompared to patients described by other research groups. The frequencies of theabnormalities were similar to other FANCG cohorts described but significant differencesto a group of FA patients from unspecified complementation groups were found. Thisdifference could be because different complementation groups are associated more or lessstrongly with specific abnormalities.It was found previously that particular congenital abnormalities in FA patients areassociated with a poor haematological outcome. We concluded that black South AfricanFANCG patients have a high risk of early development of AA even though they do nothave a high frequency of congenital abnormalities.

[发布机构] University of the Witwatersrand