Familial thrombocytosis as a recessive, possibly X-linked trait in an Arabfamily

Familial thrombocytosis (FT) has previously been described as an autosomal- dominant disorder with manifestations similar to those of sporadic essentia l thrombocythaemia. We studied an Arab family consisting of four brothers. aged 4-8 years, who had either sustained markedly elevated (> 1000 x 10(9)/ l) or moderately elevated (> 300 x 10(9)/l) platelet counts, two healthy si sters and their parents who had normal platelet counts, The four brothers w ith FT had normal plasma thrombopoietin levels and are currently not presen ting with any thrombotic or haemorrhagic complications. Mutation analysis a t the thrombopoietin gene (THPO) of the affected family members failed to d etect the intron 3 G-->C splice mutation that had been described as causing FT, In addition, segregation analysis using a polymorphic CA marker reveal ed completely discordant THPO alleles among the affected brothers. We postu late the existence of a new locus for FT whereby the disease is transmitted as a recessive, possibly X-linked trait.