Autosomal dominant macrothrombocytopenia in Italy is most frequently a type of heterozygous Bernard-Soulier syndrome

Abstract

A form of autosomal dominant macrothrombocytopenia is characterized by mild or no clinical symptoms, normal platelet function, and normal megakaryocyte count. Because this condition has so far received little attention, patients are subject to misdiagnosis and inappropriate therapy. To identify the molecular basis of this disease, 12 Italian families were studied by linkage analysis and mutation screening. Flow cytometry evaluations of platelet membrane glycoproteins (GPs) were also performed. Linkage analysis in 2 large families localized the gene to chromosome 17p, in an interval containing an excellent candidate, the GPIb␣ gene. GPIb␣, together with other proteins, constitutes the plasma von Willebrand factor (vWF) receptor, which is altered in Bernard-Soulier syndrome (BSS). In 6 of 12 families, a heterozygous Ala156Val missense substitution was identified. Platelet membrane GP studies were performed in 10 patients. Eight were distinguished by a reduction of GPs comparable to that found in a BSS heterozygous condition, whereas the other 2, without the Ala156Val mutation, had a normal content of platelet GPs. In conclusion, the current study provides evidence that most (

A family with bolzano-type Bernard–Soulier syndrome carries a benign A1939T MYH9 mutation

“…To confirm the diagnosis, we performed GPIb mutation screen. We found the heterozygous, C515T or A156V mutation (Figure 2(b)) and confirmed the diagnosis of autosomal dominant or Bolzano-type BSS in this patient/family [4,6]. BSS is a rare inherited platelet disorder, characterized by variable thrombocytopenia and large defective platelets.…”

“…The majority of BSS cases are transmitted in an autosomal recessive manner [7]. BSS cases that have an autosomal dominant trait were only recently described [4,8]. In fact, Mediterranean macrothrombocytopenia is now recognized to be an autosomal dominant form of BSS or the Bolzano-type BSS [4].…”

“…described for patients with autosomal dominant BSS [4,5]. To confirm the diagnosis, we performed GPIb mutation screen.…”

Macrothrombocytopenia in North India: Role of Automated Platelet Data in the Detection of an Under Diagnosed Entity

“…The exact molecular nature of this defect is still unclear although a few patients have been shown to be heterozygous carriers of the BSS [14]. Clinically, most patients are asymptomatic or have mild bleeding [15,16].…”

A Case Report of Bernard-Soulier Syndrome in Differential Diagnosis of Immune Thrombocytopenic Purpura.

“…†Originally reported as codon 126. [31] Female [32] 14 years old Male [33] Angiodysplasia + breast cancer + Hepatitis C 48 years old Female [34] Tuberculosis 14 years old Female [35] Hepatitis 42 years old Female [36] Coronary artery disease 68 years old Male [37] Atherosclerosis and unstable angina 66 years old Male [38] Pregnancy Variable Female [39] Aquagenicurticarial 18 years old Male [45] Developmental dysplasia of her left hip (DDH) 40 years old Female [46] Acute myeloid leukemia 21 years old Female [25] Myocardial infarction 60 and 64 years old Male [26] [63] 3233-3236delTGAG Premature termination [64] 3285C>T Leu57Phe [65] 3309T>C Cys65Arg [66] 3343delT Premature termination [67] 3502T>C Leu129Pro [68][69] 3583C>T Ala156Val [70-71-72] 3621-3656del Premature termination [72] 3651-3653delCTC del Leu179 [73] 3741T>A Cys209Ser [74][75] 3998-3999delTG Premature termination [12] 4145G>A Trp343stop [76] 4444insT Premature termination [12-14-75] 4447C>A Ser444stop [13] 4464delA Premature termination [12][13][14] 4591-4592delAt Premature termination [77-78-79] 4610G>A Trp498stop [66][67][68][69][70][71][72][73]…”