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

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.