Bernard-Soulier syndrome (BSS) is a rare autosomal recessive bleeding disorder characterized by defects of the GPIb-IX-V complex, a platelet receptor for von Willebrand factor (VWF). Most of the mutations identified in the genes encoding for the GP1BA (GPIbα), GP1BB (GPIbβ), and GP9 (GPIX) subunits prevent expression of the complex at the platelet membrane or more rarely its interaction with VWF. As a consequence, platelets are unable to adhere to the vascular subendothelium and agglutinate in response to ristocetin. In order to collect information on BSS patients, we established an International Consortium for the study of BSS, allowing us to enrol and genotype 132 families (56 previously unreported). With 79 additional families for which molecular data were gleaned from the literature, the 211 families characterized so far have mutations in the GP1BA (28%), GP1BB (28%), or GP9 (44%) genes. There is a wide spectrum of mutations with 112 different variants, including 22 novel alterations. Consistent with the rarity of the disease, 85% of the probands carry homozygous mutations with evidence of founder effects in some geographical areas. This overview provides the first global picture of the molecular basis of BSS and will lead to improve patient diagnosis and management.

Bernard-Soulier syndrome (BSS) is a rare autosomal recessive genetic disorder characterized by thrombocytopenia, circulating giant platelets, and prolonged bleeding time. BSS is explained by a defect in primary hemostasis owing to quantitative or qualitative defect in the GPIb-IX-V complex, composed of four subunits: GPIbalpha, GPIbbeta, GPIX, and GPV. In this study, we report a novel GPIbbeta defect in a Tunisian family, in which Serine 23 is substituted by a Stop codon causing a premature termination of translation. This defect was homozygous in the BSS patient and heterozygote in both the parents and sisters of the patient. We studied the effect of this mutation on the expression of the GPIb-IX complex by western blot, flow cytometry, and confocal microscopy: GPIbalpha and GPIX were absent on the surface of platelets, whereas they were present in the cytoplasm. These results led to conclude that the novel Ser 23 Stop mutation in GPIbbeta is responsible of BSS in the studied family and hampers the complex to form on the platelets surface.

GPIbα, GPIbβ, and GPIX are three candidate genes for a rare genetic bleeding disorder named Bernard Soulier syndrome (BSS). These genes are unique in the genome and encode for glycoprotein subunits of the GPIb-IX complex. Quantitative or qualitative deficiency in this complex is often associated with BSS. Here, we report the novel variant of BSS in which Ser23 of GPIbβ is substituted by a Stop codon causing a premature termination of translation, recently described in one family. This genetic defect is revealed in three unrelated BSS patients. The pedigree was determined for two families (F1 and F2) and revealed the homozygosity of the mutation in the two patients and its heterozygosity in parents. In the third family, the patient DNA was heterozygote with the same Ser23 Stop mutation in addition to two missense heterozygote mutations (Asp 51 Gly) and (Ala 55 to Pro). We studied the effect of the Ser23 Stop mutation on the expression of the complex. Our findings confirm that the identified GPIbβ mutation is responsible for the BSS phenotype and hampers the GPIb-IX complex to form on the platelets' surface. Regarding the scarcity of the BSS syndrome, the occurrence of the same mutation in three unrelated families would suggest a BSS founder mutation in Tunisia.

Venous thrombosis (VT) is a common disease with multifactorial pathogenesis. Factor V Leiden mutation (G1691A) (FVL) is the most common risk factor in venous thrombosis. The prevalence of FVL varies according to geography and ethnicity. Hence, in several countries there is a difference in the frequency of this mutation between the southern, central and north. In Tunisia, no data is available about prevalence of FVL mutation by geographical origin. For this reason, we sought the prevalence of FVL mutation in blood donor of south Tunisia population. FVL has been detected by APCR-test and confirmed by PCR-RFLP and sequencing. Two hundred fifty blood donors, different in age and sex were included in this study to determine the prevalence of FVL in blood donors. FVL mutation was found in 13.6% of the studied population. Thirty-one were heterozygous and three persons were homozygous with a rate of 12.4 and 1.2%, respectively. In conclusion, FVL mutation is very common in south Tunisian population.

The reported frequencies are more similar to those of Caucasians than those of north Tunisian population.