Abstract:
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 unknown
whether heterozygote carriers are also predisposed to developing these disorders.
The black South African population group is ideal for FA mutation screening because the
presence of a founder mutation, FANCG 637-643, makes screening relatively straight
forward. Three individuals with AML (115 screened) and one with AA (78 screened) were
found to be heterozygous for the black South African founder mutation. From our data it
seems unlikely that this mutation places heterozygous carriers of the mutation at high risk
of developing AML or AA. Three children with AA out of 26 screened, were homozygous
for the mutation. This finding reiterates the importance of screening all children with AA
for FA.
The frequency of certain congenital abnormalities in black South African FA patients was
compared to patients described by other research groups. The frequencies of the
abnormalities were similar to other FANCG cohorts described but significant differences
to a group of FA patients from unspecified complementation groups were found. This
difference could be because different complementation groups are associated more or less
strongly with specific abnormalities.
It was found previously that particular congenital abnormalities in FA patients are
associated with a poor haematological outcome. We concluded that black South African
FANCG patients have a high risk of early development of AA even though they do not
have a high frequency of congenital abnormalities.
