Clinical and Genetic Characterization of Factor XI Deficiency in Jordan: Identification of a Novel Splice-Site Mutation Associated with Severe Deficiency.

BackgroundFactor XI (FXI) deficiency is a rare bleeding disorder, common among Ashkenazi Jews. Affected individuals may present severe bleeding after trauma or surgery, which requires careful management. To date FXI deficiency has not been genetically or clinically described in the Jordanian population.Material and methodsSeventeen patients (median age 29) from 16 Jordanian Arab families, referred to the hemostasis and thrombosis laboratory at the University of Jordan, due to bleeding history or prolonged activated partial thromboplastin time. FXI deficiency was confirmed by factor assay (cutoff: ≤ 40% activity). Bleeding score was recorded, and Next Generation Sequencing of the F11 gene was utilized to detect causative mutations.ResultsOf the 17 patients, 14 had severe FXI deficiency. The median bleeding score was 6. Five patients carried the known p.Glu135Ter (type II), while ten patients had different point mutations. Three patients with severe FXI deficiency were found to carry previously undescribed variants, including one novel splice site mutation (c.1136-1G > C). No pathogenic variants were identified in two patients.DiscussionThis is the first study of FXI deficiency in Jordanian Arabs, which revealed fourteen patients with severe FXI deficiency. Ten mutations were identified, including one novel splice-site mutation. The relevance of type II mutation in our cohort suggested a founder effect similar to Jewish ancestry. Bleeding severity was incongruent with FXI activity. Despite the small cohort and lack of functional assays, this study expands the mutational spectrum and provides new insights into FXI deficiency in Arab populations.