Hemophilia genotyping is a high-yield test, with reportable variants identified in more than 98% of patients with type A and B disease. This is the conclusion of the largest hemophilia genotyping project to date, called MyLifeOurFuture.
“Our findings support the need for comprehensive genotyping approaches in order to accurately detect the presence of multiple variants and structural variation,” researchers wrote in a report they published in the Journal of Thrombosis and Haemostasis.
MyLifeOurFuture is a US initiative to better understand hemophilia. For the project, 11,341 people who have the disease or are potential carriers of it were genotyped at 107 hemophilia treatment centers between 2013 and 2017.
Of these, 8976 were tested for hemophilia A, 2358 were tested for hemophilia B, 3 were tested for both hemophilia A and hemophilia B, and 4 were tested for hemophilia not otherwise specified.
The results showed genetic variants in most males, which included 1914 unique variants. Of these, 1482 were in the F8 gene and 431 were in the F9 gene. A total of the 744 variants were novel.
Read more about the epidemiology of hemophilia.
Among patients with severe hemophilia A, those with the highest rate of inhibitors had large deletions in the F8 gene. This was followed by complex intron 22 inversions and no variants. The same was through for severe hemophilia B, where those with the highest rate of inhibitors had large deletions in the F9 gene.
Almost a third (27.3%) of Black patients had inhibitors, while only 16.2% of White patients had inhibitors.
The authors concluded that the MyLifeOurFuture initiative contributed to the understanding of variation in the F8 and F9 genes and their impact on disease severity and inhibitor formation.
Hemophilia is a rare inherited hematological disease characterized by the deficiency of blood clotting factors. Hemophilia A is thought to affect around 1 in 4000 to 1 in 5000 live male births and is thought to be about 4 times more common than hemophilia B.
Johnsen JM, Fletcher SN, Dove A, et al. Results of genetic analysis of 11,341 participants enrolled in the My Life, Our Future hemophilia genotyping initiative in the United States. J Thromb Haemost. Published online June 29, 2022. doi:10.1111/jth.15805