JAK2V617F mutation is common in old patients with polycythemia vera and essential thrombocythemia.

Background: JAK2V617F mutation occurs in 90% of polycythemia vera (PV) and in 50% of essential thrombocythemia (ET) patients.

Materials And Methods: 253 consecutive patients affected by myeloproliferative disorders (MPD, 121 PV, 132 ET) were evaluated and stratified in 4 age groups: 18-39, 40-59, 60-75 and over 75 years (>75). The JAK2V617F mutation was searched and its allele burden was evaluated.

Src tyrosine kinase preactivation is associated with platelet hypersensitivity in essential thrombocythemia and polycythemia vera.

Polycythemia vera (PV) and essential thrombocythemia (ET) are chronic myeloproliferative disorders characterized by an increased incidence of thrombo-hemorrhagic complications. The acquired somatic Janus kinase 2 (JAK2) V617F mutation is present in the majority of PV and ET patients. Because aberrant protein Tyr-phosphorylation has been associated with hematopoietic malignancies, the activity of the tyrosine kinases Src and JAK2 was analyzed in resting and thrombin-stimulated platelets from 13 PV and 42 ET patients.

Hydroxyurea in old patients with essential thrombocythemia.

Background And Aims: A previous thrombotic event and advanced age are well-known risk factors for thrombosis in essential thrombocythemia (ET). In these patients, therefore, cytotoxic drugs are needed to reduce platelet count. In spite of this convincing idea, in clinical practice, some old patients do not use platelet-reducing drugs, for a variety of causes, and few specific studies in old patients with ET are available.

Genetic study in patients with factor XII deficiency: a report of three new mutations exon 13 (Q501STOP), exon 14 (P547L) and -13C>T promoter region in three compound heterozygotes.

A group of 29 patients with congenital factor XII (FXII) deficiency belonging to nine distinct families have been investigated. All were cases of true deficiency in the sense that there was no discrepancy between FXII activity and FXII antigen. From a clotting point of view, 11 patients appeared homozygous, as both FXII activity and antigen were very low (< or =1% and traces of antigen).

Novel point mutation in a leucine-rich repeat of the GPIbalpha chain of the platelet von Willebrand factor receptor, GPIb/IX/V, resulting in an inherited dominant form of Bernard-Soulier syndrome affecting two unrelated families: the N41H variant.

In Italy, a significant proportion of patients with autosomal dominant inheritance of macrothrombocytopenia have been recognized as having heterozygous Bernard-Soulier syndrome carrying the Bolzano-type defect. This condition prompted a systematic review of our out-patients with chronic isolated macrothrombocytopenia. We recognized that the affected members of two unrelated families represented a new variant of heterozygous Bernard-Soulier Syndrome with autosomal dominant inheritance.

A case of Bernard-Soulier Syndrome due to a homozygous four bases deletion (TGAG) of GPIbalpha gene: lack of GPIbalpha but absence of bleeding.

More than 20 DNA mutations with different inheritance pattern have been described in patients with Bernard-Soulier Syndrome (BSS), leading to abnormal or absent synthesis and/or expression of GPIbalpha. Clinical phenotype shows considerable variation between individuals, such as bleeding, platelet count and the percentage of large platelets. We describe in a BSS patient the first case of homozygous four bases deletion (TGAG) in the gpIbalpha gene coding sequence, leading to a premature stop codon.

Increased risk of pregnancy complications in patients with essential thrombocythemia carrying the JAK2 (617V>F) mutation.

Essential thrombocythemia (ET) may occur in women of childbearing age. To investigate the risk of pregnancy complications, we studied 103 pregnancies that occurred in 62 women with ET. The 2-tailed Fisher exact test showed that pregnancy outcome was independent from that of a previous pregnancy.

Pediatric patients with essential thrombocythemia are mostly polyclonal and V617FJAK2 negative.

Essential thrombocythemia (ET) is rare in children, and little or no information is available about clonality or JAK2 mutations. However, the analyses in this work prove useful for the diagnosis of adult myeloproliferative disorders (MPDs). We evaluated the clonality status and V617FJAK2 mutation in 20 children affected by ET and compared them with 47 consecutive adult ET cases.

Distinct promoters determine alternative transcription of gpx-4 into phospholipid-hydroperoxide glutathione peroxidase variants.

A nuclear variant of phospholipid-hydroperoxide glutathione peroxidase (PHGPx, GPx-4) was considered to be derived from alternative pre-mRNA splicing in testis and to regulate sperm maturation. The genomic sequence of rat gpx-4 was established and investigated in respect to expression into the cytosolic, mitochondrial, and nuclear forms of PHGPx. In silico analysis suggested the presence of two distinct promoter regions, the upstream one leading to transcripts translating into cPHGPx or mPHGPx and the downstream one yielding nPHGPx.

Genetic variations of gpx-4 and male infertility in humans.

Phospholipid hydroperoxide glutathione peroxidase (PHGPx), the product of gpx-4, is the major selenoprotein in sperm and is considered essential for fertilization because of its multiple roles in spermatogenesis, such as hydroperoxide detoxification, formation of the mitochondrial capsule, and chromatin condensation. Genomic DNA sequences of 3.148 kilobases covering the whole gpx-4 and its flanking regions were amplified from 63 men using the polymerase chain reaction and were analyzed for polymorphisms by direct sequencing.