The impact of motherless paternity testing in a South African population.

BACKGROUND: Paternity investigations play an important role in determining biological relatedness, and in South Africa, the outcome of these investigations impacts medical, judicial and home affairs decisions. Short Tandem Repeat (STR) analysis is utilised to perform paternity and kinship analysis, due to the polymorphic nature of STR loci. The cost associated with paternity testing is high, and there is a demand for motherless testing. OBJECTIVES: This study aims to determine what the impact of motherless testing would have been by evaluating 6182 paternity trio cases. METHODS: The AmpFLSTR™ Identifiler™ PCR Amplification kit was used to profile each of the trio cases. A scenario was created where the mother was eliminated from the test results to determine if the paternity outcome would change. RESULTS: Putative fathers were excluded in 27% of all cases, and in 2.5% of those cases, putative fathers would have been falsely included, had the mother not been tested. These false inclusions are attributed to coincidental STR loci that are shared between the mother and the putative father. The addition of loci to the STR profiling kit may resolve the issue; however, comparable STR data with more loci will have to be evaluated to ensure it overcomes the issue of coincidentally shared loci between unrelated individuals. CONCLUSION: We would recommend that within our setup and within similar setups, the mother always be included for testing, except in extreme scenarios such as death. False inclusion of putative fathers could have serious legal implications for testing laboratories.

Molecular characterisation of NPM1 and FLT3-ITD mutations in a central South African adult de novo acute myeloid leukaemia cohort.

BACKGROUND: Recognition of molecular abnormalities in acute myeloid leukaemia (AML) has improved our understanding of its biology. NPM1 and FLT3-ITD mutations are recurrent in AML and clinically significant. NPM1 mutations are associated with a favourable prognosis, while FLT3-ITD mutations are an independent poor prognostic factor in AML. OBJECTIVE: This study described the prevalence and molecular characteristics of the NPM1 and FLT3-ITD mutations in a newly diagnosed AML patient cohort in central South Africa. METHODS: The study included 40 de novo AML patients. An NPM1 and FLT3-ITD multiplex polymerase chain reaction assay was optimised to screen patients for the respective mutations and were confirmed using Sanger sequencing. The prevalence of the NPM1 and FLT3-ITD mutations were determined, and mutation-specific characteristics were described in relation to patients' demographic information and AML classifications. RESULTS: The patients' median age was 38.5 years, with 77.5% (n = 31) of patients being self-proclaimed Black Africans. AML with recurrent genetic abnormalities was most prevalent (57.5%; n = 23), of which acute promyelocytic leukaemia (APL) was most common (40.0%; n = 16). None of the patients had the NPM1 mutation. FLT3-ITD was present in 37.5% (6/16) of APL patients and in one (20.0%) of five AML patients with a t(8;21) translocation. Most patients had an FLT3-ITD allele ratio of ≥ 50% and ITD lengths of > 39 bp. CONCLUSION: FLT3-ITD mutations were mainly found in APL cases at a similar prevalence as reported in the literature. High FLT3-ITD allele ratios and long ITD lengths predominated. No NPM1 mutations were detected.

HLA major allele group frequencies in a diverse population of the Free State Province, South Africa.

BACKGROUND: Human Leucocyte Antigens (HLA) play a vital role in disease pathogenesis and transplant rejection. HLA-typing is a useful tool in predicting disease progression and to identify potential organ donors. Due to human migration and known ethnic variation, frequent targeted HLA sequencing of specific populations is crucial to increase their representation in global reference panels. MATERIALS AND METHODS: We performed a retrospective file audit of all HLA-typings done in our setting from 2005-2019. We discuss data for the major HLA-A, HLA-B, HLA-C, and HLA-DRB1 allele groups. RESULTS: Overall, the most common allele groups were HLA-A∗02, HLA-B∗15, HLA-C∗07 and HLA-DRB1∗03. For the African descent group, the most common alleles were HLA-A∗30, HLA-B∗15, HLA-C∗07 and HLA-DRB1∗03. For the European descent group, the most common alleles were HLA-A∗02, HLA-B∗07, HLA-C∗07 and HLA-DRB1∗15. For the mixed ancestry group, the most common allele groups were HLA-A∗02, HLA-B∗15, HLA-C∗02 and HLA-DRB1∗13. HLA-B∗44 was identified as the most common allele group in patients with renal failure. DISCUSSION AND CONCLUSION: The significant variation within the HLA frequencies between the different ethnic groups highlights the value of population-specific HLA-typing. Furthermore, the identification of HLA-B∗44 as a prominent HLA in our renal failure population warrants in-depth investigation of this group.