PB0167 - DE NOVO INTRON 22 INVERSION CARRIER DETECTION – THE EMERGING VALUE OF GENETIC ANALYSIS IN A DEVLOPING COUNTRY

Background: Hemophilia A (HA) is an X-linked recessive bleeding disorder characterized by the deficiency of coagulation factor VIII. Variant analysis of the Factor 8 gene (F8) forms part of the comprehensive approach to treating and managing people with hemophilia A (PWH). Importantly, it plays a vital role in carrier screening. Resource constraints have limited the use of variant analysis tools in PWH in developing countries. However, developing more cost-effective tools can make this a common practice if broader clinician buy-in is secured.

Aims: This study aimed to highlight the wide-ranging impact F8 variant analysis could potentially have on PWH and their extended families.

Methods: A gel-based in-house Polymerase Chain Reaction (PCR) method was used to determine the intron 22 inversion (inv22) status in a family where a young boy, without a family history, was recently diagnosed with hemophilia A. FVIII levels for both individuals were determined. Pedigree analysis was performed on the extended family as part of the screening work-up. Study ethics approval was obtained (UFS-HSD2020/1037/2710).

Results: Inv22 was detected in the proband and his mother but was absent in the direct family members. It was therefore deduced that the causative variant was a de novo variant in the mother, which is hypothesized to have occurred during spermatogenic meiosis in the unaffected maternal grandfather. Subsequently, this result has bearing on at least 23 direct blood relatives in this family.

Conclusion(s): The availability and utilization of cost-effective variant analysis tools in PWH are vital, not only in their management but also in their extended families. This case report highlights the value of variant analysis in a developing county where the goal is to strive for a comprehensive management approach. In addition, it should be noted that although the inv22 variant is mostly familial in HA, de novo cases are possible and should be investigated.