We report, for the first time, a non-syndromic infant with a reversible myeloproliferative disease that harbors a germline hereditary thrombopoietin (THPO) gene mutation, a condition that is known to induce familial thrombocytosis at increasing age.
In conclusion, lack of a molecular lesion within either TPO or cMpl genes indicate that HT may be caused by factors other than TPO-cMpl axis in this family.
Interestingly, decreased c-MPL and elevated PRV-1 also were observed in patients with hereditary thrombocythemia (HT) who carry a mutation in the thrombopoietin (TPO) gene.
Mutation analysis at the thrombopoietin gene (THPO) of the affected family members failed to detect the intron 3 G-->C splice mutation that had been described as causing FT.
Recent studies have shown that four kindreds with hereditary thrombocythaemia (HT) have point mutations in the 5'-untranslated region (UTR) of the TPO gene which lead to increased TPO translation.
Genetic linkage analysis with TPO microsatellite markers excluded TPO as the disease gene in the Spanish HT family, and sequencing of the TPO gene revealed no mutations in the propositus of the US family.
The contribution of increased TPO protein synthesis by a translational mechanism was recently appreciated as the cause for hereditary thrombocythemia and will have to be elucidated in other conditions of thrombocytosis in association with increased TPO levels.
Hereditary thrombocythemia (sometimes called familial essential thrombocythemia or familial thrombocytosis) can be caused by mutations in upstream AUG codons in the 5'-UTR of the TPO mRNA that normally function as translational repressors.
In a Dutch family with eleven affected individuals, the thrombopoietin protein (TPO) concentrations in serum were consistently elevated in individuals with HT.
Hereditary thrombocythemia (HT) has been described as a rare benign disorder caused by mutations in the thrombopoietin (THPO) or the c-Mpl receptor genes.
In a group of 36 Mexican mestizo patients with MPN, we studied five molecular markers: The BCR/ABL1 fusion gene, the JAK2 V617F mutation, the JAK2 exon 12 mutations, the MPLW515L mutation and the MPLW515K mutation; 17 patients with essential thrombocythemia (ET), eight with polycythemia vera (PV), four with primary mielofibrosis (MF), five with undifferentiated MPN, one with primary erythrocytosis and one with familial thrombocytosis.
Interestingly, decreased c-MPL and elevated PRV-1 also were observed in patients with hereditary thrombocythemia (HT) who carry a mutation in the thrombopoietin (TPO) gene.