De Novo Intron 22 Inversion Carrier Detection—The Emerging Value of Genetic Analysis in a Developing Country. (September 2021) - Kloppers, Jean F.
Genetic analysis of the F8 gene can play a vital role in the diagnosis and management of people with hemophilia A (PWH). Knowing the causative mutation can assist treating clinicians in predicting the risk of inhibitor formation and a person's response to treatment. It is also a vital tool for genetic counselors in assisting PWH with family planning. Mutational analysis has been limited in developing countries, mainly due to resource constraints; however, with the development of more cost-effective screening tools, these assays are becoming more common in developing countries. Unfortunately, the clinical utility of these assays remain unclear in some of these underresourced countries, resulting in a lack of clinician buy-in. We aimed to highlight the wide-ranging impact mutational analysis potentially has on PWH and their extended families in a developing country. We used a gel-based in-house method to determine the inversion 22 (Inv22) mutation in a family where a young boy, without a family history, was recently diagnosed with hemophilia A. Inv22 was detected in the proband and his mother, but not in any other direct family member. Therefore, we concluded that the mutation was a de novo mutation in the mother. Subsequently, this result has bearing on at least 23 direct blood-relatives. Genetic screening extends far wider than the treatment of PWH and is vital in the management of PWH and their extended families. With the availability of cost-effective genetic screening assays this should also be the case in developing countries.