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The first two confirmed sub-Saharan African families with germline TP53 mutations causing Li-Fraumeni syndrome

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Abstract

Li-Fraumeni syndrome is a rare inherited cancer syndrome characterised by the early onset of specific cancers. Li-Fraumeni syndrome (LFS) is associated with germline mutations in the tumour suppressor gene, TP53. This study reports the first cases of molecularly confirmed LFS germline mutations in sub-Saharan Africa. Three black African patients, all with LFS-associated cancers, were seen through the Clinical and Counselling Section of the Division of Human Genetics at the National Health Laboratory Service and University of the Witwatersrand in Johannesburg, South Africa, during 2011–2012. All three patients (two were related) were recruited into this research study. Sequence analysis of the coding region of the TP53 gene identified a Class IV (likely pathogenic) variant, c.326T > C (p.Phe109Ser), in the two related patients, and a known pathogenic mutation, c.1010G > A (p.Arg337His), also referred to as the Brazilian founder mutation, in the other patient. A confirmed diagnosis in these patients will assist in tailored medical management (it is recommended that individuals carrying a germline TP53 mutation avoid radiotherapy as this might cause secondary radiotherapy-induced malignancies) and in addition, genetic testing of at-risk family members can be offered. Very little is known and documented on LFS in African individuals. Despite the small number of patients in this study, the results support the need for diagnostic genetic testing for LFS in South Africa.

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Acknowledgements

The authors would like to thank the Faculty Research Committee (FRC) of the University of the Witwatersrand’s Faculty of Health Sciences for funding this study through an FRC Individual Grant.

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Authors and Affiliations

  1. Division of Human Genetics, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

    Shelley Macaulay, Quintin Clive Goodyear, Mia Kruger, Wenlong Chen, Fahmida Essop & Amanda Krause

  2. Division of Human Genetics, The National Health Laboratory Service, Johannesburg, South Africa

    Shelley Macaulay, Quintin Clive Goodyear, Fahmida Essop & Amanda Krause

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  1. Shelley Macaulay
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Correspondence to Shelley Macaulay.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Appendix

Appendix

See Figs. 3 and 4.

Fig. 3
figure 3

Electropherogram of exon four in Patient A which illustrates the presence of the variant c.326T > C (as indicated by the arrow) which causes a missense codon change TTC-TCC. The sequence above the electropherogram refers to the reference sequence. This variant was also identified in Patient B

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Fig. 4
figure 4

Electropherogram of exon ten in Patient C in whom the c.1010G > A mutation was identified (as indicated by the arrow). This mutation causes a missense codon change CGC–CAC. The sequence above the electropherogram refers to the reference sequence

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Macaulay, S., Goodyear, Q.C., Kruger, M. et al. The first two confirmed sub-Saharan African families with germline TP53 mutations causing Li-Fraumeni syndrome. Familial Cancer 17, 607–613 (2018). https://doi.org/10.1007/s10689-018-0075-5

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