Hemophilia A and B are X-linked recessive bleeding disorder caused by variants in the factor VIII (FVIII) and factor IX (FIX) genes. There is correlation between the type of mutation and clinical severity of these patients. Establishing national screening program for haemophilia patients is highly encouraged by the World Health Organization (WHO) and World Federation of Haemophilia (WFH). Hence we aimed to establish a genotypic data base for the nature of mutations present in Saudi population.

This retrospective descriptive study on a cohort of 136 Saudi hemophilia A and B patients.

Molecular studies were performed to identify known and novel causative variants in hemophilia A and B families and correlated with some clinical features.

There were 129 male and 7 females with age ranged from 2 - 62 years old, 97 (71.3%) hemophilia A (HA) and 39 (28.7%) hemophilia B (HB). The clinical severity of hemophilia A ranged between mild (10, 10.3%), moderate (2, 2.1%) and severe (83, 85.6%), while for hemophilia B (mild 13 (33.3%), moderate 2 (5.1%) and severe 24 (61.5%) respectively. There were 76 (55.9%) had chronic joint disability. Factor inhibitors with different titers were detected in 24 (24.7%) of HA and only 2 (5.1%) of HB. Out of the whole cohort 136 had been tested for causative variants, 17 (12.5%) were positive for inv-22 and 4 (2.9%) for inv-1, while all negative HA were selected for analysis by next generation sequencing. We are reporting 3 cases of females with severe forms of hemophilia.We are reporting different mutations that was consistent in group of tested members of same family /trip. We confirmed as previously reported high frequency of inv 22 and we found 7 novel mutation out 12 detected variants for HA and one novel mutation out of 13 detected variants for HB.

These results will enrich the spectrum of variants and enlarge the factor VIII and factor IX proteins database in the Saudi Arabian population. Establishing a molecular genetic based tests for fast, easy, and cost effective reliable mutation screening that can also be applied in the future for prenatal and pre-implantation genetic diagnosis.