The trend appears to indicate that physical anomalies (radial defects, renal malformations) may be more common in Afrikaner FA patients with FANCA mutations, and suggests that analysis of a larger Afrikaner cohort may be beneficial in determining whether this trend is significant.
FANCA mutations account for the highest percentage of FA patients worldwide as documented by the IFAR.
Two large international studies characterised the clinical phenotype of individuals with different mutations in the FANCA gene.
[17,18] It is now known that the majority of Afrikaner patients with FA harbour founder FANCA mutations as the cause of their condition.
Previous reports differed vastly in their reporting of the percentage of patients with FANCA mutations who meet the diagnostic criteria for VACTERL/H association, with figures of between 3% and 20%.
An area for future research includes a molecular screen for FANCA mutations in Afrikaner patients with VACTERL/H association.
Targeted resequencing revealed a novel truncating mutation, c.3446_3449dupCCCT (p.Met1151ProfsTer65), in exon 35 of the FANCA gene (NM_000135.2), in the heterozygous form in patient 1 and homozygous form in patient 2.
The results of the NGS (next generation sequencing) analysis were confirmed by direct DNA sequencing of exon 35 of the FANCA gene (Figure 1).
The two patients described here had a clinical presentation of FA, but only one was heterozygous for the exon 3 deletion of the FANCA gene.
Origin, functional role, and clinical impact of Fanconi anemia FANCA mutations.