Hematological consequences of a FANCG founder mutation in Black South African patients with Fanconi anemia

Screening for mutations in two exons of FANCG gene in Pakistani population

“…The most common presenting complaint in our cohort of patients has been recurrent infections (present in 100% of patients) and bleeding tendencies (present in 82% of patients) with the most frequent site of the bleeding being nose. This finding is consistent with most other publications 32,37 . Pallor is also a very frequent finding in most studies done worldwide 40 .…”

“…This trend of variance in the prevalence of FA genes exists for all FA genes. For example, Ashkenazi Jews have the FANCC as the most prevalent genetic mutation because of the founder effect of IVS4 +4 A>T mutation 32 . A study done recently in Egypt on four exons of FANCA gene has revealed no mutation found to the researchers' surprise as FANCA is the most prevalent gene throughout the world so far 33 .…”

Fanconi anaemia in South Africa: Past, present and future

“…[1,26] Genotype-phenotype correlation studies performed in the black and Afrikaner populations in SA show that the frequencies of physical anomalies mirror the IFAR data in some respects, but also highlight population-and possibly mutation-specific features in our patient cohorts (Table 2). [4][5][6] A trend towards significant physical differences between the two founder populations in SA has also been noted and suggests that future research is needed to provide greater definition, particularly for the Afrikaner phenotype. [6] It has been observed that in both population groups, identification and recognition of the FA phenotype may be improved by referral of children with growth restriction, pigmentary anomalies and unusual hands to a paediatrician or medical geneticist for an assessment.…”

“…[8] Based on haplotype analysis and evaluation of population genetic data, a founder mutation in the black population (FANCG: NM_0046 29.1g.35077270_35077264del) appears to predate the arrival of Bantu speakers in southern Africa in AD 400, and is therefore an ancient mutation, possibly with its origins in West Africa. [2,5] The estimated carrier frequency of the mutation is 1/100, with the predicted birth incidence of FA in black South Africans approximating 1/40 000. [2] Molecular and genealogical evidence indicates that the three Afrikaner founder mutations (FANCA: NM_000135.2 g.89858955_89818546del; NM_000135.2 g.89847979_89861587del; NM_000135.2 g.89813249_89813249del) were probably introduced into SA following the 17th-century migration of the French Huguenots to the Cape.…”

Fanconi Anaemia in South African Patients with Afrikaner Ancestry

“…[14] The physical and haematological phenotypes of black patients, homozygous for the 7 bp deletion mutation, have been characterised previously. 15,16] In SA individuals with Afrikaner ancestry, three null mutations in FANCA (del E12-31 (deletion mutation of exons 12 to 31); del E11-17 (deletion mutation of exons 11 to 17) and 3398delA (point mutation at position 3398)) have previously been shown to account for ~80% of FA cases. [13] Molecular and genealogical evidence has confirmed that these founder FANCA mutations were probably introduced into SA following the 17th century migration of the French Huguenots to the Cape.…”