n South African Medical Journal - Fanconi anaemia in black South African patients heterozygous for the c.637-643delTACCGCC founder mutation : Festschrift : Professor Trefor Jenkins - medical genetics

Volume 103, Issue 12
  • ISSN : 0256-9574
  • E-ISSN: 2078-5135



Fanconi anaemia (FA) is an autosomal recessive, genetically heterogeneous disorder, characterised by interstrand crosslink-induced chromosome breaks, congenital abnormalities and predisposition to malignancies. It has a prevalence of about 1/40 000 in black South Africans (SAs). A founder mutation in the gene occurs in the homozygous state in 77.5% of southern African blacks.

To locate additional pathogenic mutations in the gene of black FA patients who were heterozygous for the founder mutation.
Further mutation analysis of the gene was undertaken in 7 patients clinically suspected of having FA. The parents of two of the patients were tested for the presence of the founder mutation to determine true heterozygosity in the patients. To clarify whether or not previously unreported variants were pathogenic, 58 random black SA individuals were screened.
Three novel single base pair deletions, resulting in frameshift mutations (c.247delA, c.179delT and c.899delT) were identified in 3/7 patients. A fourth patient was found to have a single base substitution resulting in a splice site mutation (c.1636+1G>A). The remaining three patients were not found to harbour any pathogenic mutations. Two non-pathogenic variants were also identified among the seven patients.
The results of this small sample suggest that a second common mutation in the gene is unlikely in this population. However, sequencing should be performed on patients heterozygous for the common founder mutation to attempt to confirm their diagnosis.

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