Subject(s)
Bernard-Soulier Syndrome/genetics , Platelet Glycoprotein GPIb-IX Complex/genetics , Adolescent , Adult , Bernard-Soulier Syndrome/epidemiology , Child , Child, Preschool , Female , France/epidemiology , Humans , Infant , Infant, Newborn , Male , Middle Aged , Mutation , Prevalence , Reunion , Young AdultABSTRACT
Glanzmann thrombasthenia (GT) and Bernard-Soulier syndrome (BSS) are two rare inherited disorders of platelet function. In this study, we report the demographic, clinical and biological characteristics of 23 patients with GT and of seven patients with BSS from southern Iran who had been followed for many years but fully characterized only recently, when platelet aggregation tests and flow cytometric studies became available for the first time in the country. We found a high prevalence of both diseases that can be explained by the high rate of consanguineous marriages in south Iran. Patients affected by GT and BSS suffer mainly from mucocutaneous bleedings causing anemia and transfusion requirements.
Subject(s)
Bernard-Soulier Syndrome/epidemiology , Thrombasthenia/epidemiology , Adolescent , Adult , Anemia/etiology , Anemia/therapy , Bernard-Soulier Syndrome/complications , Bernard-Soulier Syndrome/diagnosis , Blood Transfusion/statistics & numerical data , Child , Child, Preschool , Consanguinity , Flow Cytometry , Follow-Up Studies , Hemorrhage/etiology , Hemorrhage/therapy , Humans , Iran/epidemiology , Platelet Aggregation , Platelet Function Tests , Prevalence , Thrombasthenia/complications , Thrombasthenia/diagnosisSubject(s)
Arteriosclerosis/epidemiology , Bernard-Soulier Syndrome/epidemiology , Platelet Membrane Glycoproteins/deficiency , Thrombasthenia/epidemiology , Arteriosclerosis/blood , Arteriosclerosis/etiology , Arteriosclerosis/physiopathology , Bernard-Soulier Syndrome/blood , Bernard-Soulier Syndrome/ethnology , Blood Platelet Disorders/epidemiology , Blood Platelet Disorders/genetics , Blood Platelets/metabolism , Cytokines/metabolism , Cytoplasmic Granules/metabolism , DNA Mutational Analysis , Disease Susceptibility , Ethnicity/genetics , Female , Genetic Heterogeneity , Growth Substances/metabolism , Humans , Male , Mutation , Myocardial Infarction/epidemiology , Platelet Adhesiveness , Platelet Aggregation , Platelet Glycoprotein GPIIb-IIIa Complex/genetics , Platelet Glycoprotein GPIIb-IIIa Complex/physiology , Platelet Glycoprotein GPIb-IX Complex/genetics , Platelet Glycoprotein GPIb-IX Complex/physiology , Platelet Membrane Glycoproteins/genetics , Platelet Membrane Glycoproteins/physiology , Receptors, Vitronectin/genetics , Receptors, Vitronectin/physiology , Sequence Deletion , Thrombasthenia/blood , Thrombasthenia/ethnologyABSTRACT
Bernard-Soulier syndrome (BSS) is a rare hereditary bleeding disorder and macrothrombocytopenia which is caused by a defect in the platelet glycoprotein Ib/IX/V (GP Ib/IX/V) complex, the receptor for von Willebrand factor and thrombin. Here we report the molecular basis of the classical form of BSS in two unrelated Finnish patients, both with a life-long history of severe bleeding. Flow cytometry and immunoblotting showed no expression of GP Ib/IX, GP Ib alpha, GP Ib beta or GP IX (less than 10%) in the patients' platelets. No expression of GP V (< 10%) was observed in propositus 1, but a residual amount was found in propositus 2 (24%). DNA sequencing analysis revealed that propositus 1 was compound heterozygous for a two-base-pair deletion at Tyr505(TAT) and a point mutation Leu129(CTC)Pro(CCC) in the GP Ib alpha gene. Propositus 2 was homozygous for the Tyr505(TAT) deletion. The nine relatives who were heterozygous for either of the mutations also had low levels of GP Ib alpha (74-90%). Hence, Bernard-Soulier patients homozygous or compound heterozygous for Tyr505(TAT) are severely affected. Interestingly, both mutations have independently been found in three other families in previous reports, suggesting their ancient age or mutational 'hot spot'.
