Festschrift: Professor Jenkins

Fanconi anaemia in black South African patients heterozygous for the FANCG c.637-643delTACCGCC founder mutation

Tasha Wainstein, Robyn Kerr, Claire L Mitchell, Smita Madaree, Fahmida B Essop, Elana Vorster, Rosalind Wainwright, Janet Poole, Amanda Krause

Abstract


Background. 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 FANCG gene occurs in the homozygous state in 77.5% of southern African blacks.

Objective. To locate additional pathogenic mutations in the FANCG gene of black FA patients who were heterozygous for the founder mutation.

Methods. Further mutation analysis of the FANCG 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.

Results. 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.

Conclusion. The results of this small sample suggest that a second common mutation in the FANCG gene is unlikely in this population. However, FANCG sequencing should be performed on patients heterozygous for the common founder mutation to attempt to confirm their diagnosis. 


Authors' affiliations

Tasha Wainstein, Division of Human Genetics, School of Pathology, National Health Laboratory Service and Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

Robyn Kerr, Division of Human Genetics, School of Pathology, National Health Laboratory Service and Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

Claire L Mitchell, Division of Human Genetics, School of Pathology, National Health Laboratory Service and Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

Smita Madaree, Division of Human Genetics, School of Pathology, National Health Laboratory Service and Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

Fahmida B Essop, Division of Human Genetics, School of Pathology, National Health Laboratory Service and Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

Elana Vorster, Division of Human Genetics, School of Pathology, National Health Laboratory Service and Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

Rosalind Wainwright, Division of Haematology and Oncology, Department of Paediatrics, Chris Hani Baragwanath Academic Hospital and Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

Janet Poole, Division of Haematology and Oncology, Department of Paediatrics, Charlotte Maxeke Johannesburg Academic Hospital and Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

Amanda Krause, Division of Human Genetics, School of Pathology, National Health Laboratory Service and Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

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Keywords

Fanconi anaemia; founder mutation; FANCG; festschrift; Trefor Jenkins; human genetics

Cite this article

South African Medical Journal 2013;103(12):970-973. DOI:10.7196/SAMJ.7215

Article History

Date submitted: 2013-06-30
Date published: 2013-10-11

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