Atypical haematological presentation in a case of polycythaemia vera with a new variant mutation detected in exon 12: c.1605G>T (p.Met535Ile)

2017 ◽  
Vol 71 (2) ◽  
pp. 180-184 ◽  
Author(s):  
Amélia Soraia Andrade Pita ◽  
Ana Paula da Silva Azevedo ◽  
Alice Reichert ◽  
Cândido José Pimenta da Silva ◽  
Vanessa Henriques ◽  
...  

One of the major genetic insights into the pathogenesis of polycythaemia vera included the identification of the somatic point gain-of-function mutations in Janus kinase 2 gene—first JAK2V617F on exon 14, present in 95%–97% of the cases, and later on exon 12. In the literature, we can find some reported studies where different exon 12 mutations are identified. Unlike patients with JAK2V617F mutation in exon 14, the mutation at exon 12 is not usually associated with an increase in the three haematopoietic series (erythrocytosis, leucocytosis and thrombocytosis). It appears to be associated with a distinct syndrome, mostly characterised by isolated and more marked erythrocytosis, independently of the mutational variant. We report here the case of a patient who is JAK2exon 12 positive, presenting a novel mutation—c.1605G>T (p.Met535Ile)—associated with c.1612C>T (p.His538Tyr) mutation previously described, evidencing an atypical clinical phenotype.

2007 ◽  
Vol 148 (5) ◽  
pp. 203-210 ◽  
Author(s):  
Hajnalka Andrikovics ◽  
Anikó Szilvási ◽  
Nóra Meggyesi ◽  
Viktória Király ◽  
Gabriella Halm ◽  
...  

The Val617Phe point mutation of Janus kinase 2 gene is believed to participate in the pathogenesis of myeloproliferative syndrome characterised by the clonal alteration of hematopoetic stem cells. According to current results, the frequency of Val617Phe activating mutation is around 80% in polycythaemia vera, 35% in essential thrombocythaemia, and 50% in chronic idiopathic myelofibrosis. The diagnoses of polycythaemia vera, essential thrombocythaemia and idiopathic myelofibrosis were so far based on the exclusion of secondary factors as well as bone marrow biopsy histology. The goal of the present work was to establish simple molecular genetic techniques for the routine testing of Janus kinase 2 gene Val617Phe mutation, and to compare the clinical phenotypes of Val617Phe mutation positive and negative myeloproliferative syndromes. We employed the allele specific polymerase chain technique for detection of Val617Phe mutation in 252 patients with myeloproliferative syndrome. We measured Val617Phe frequency as 85,4% (117/137) in polycytaemia vera, 56,6% (56/99) in essential thrombocythaemia, and 87,5% (14/16) in idiopathic myelofibrosis. We found significantly elevated hemoglobin levels and white blood cell counts (measured at the time of diagnosis) in Val617Phe-positive polycythaemia vera and essential thrombocythaemia patient groups compared to Val617Phe-negative patients. However, the frequencies of splenomegaly and other complications (thrombosis, bleeding, transformation to acute leukemia) were not significantly different between the mutation-positive and negative groups. In conclusion, the non-invasive mutation analysis of the Janus kinase 2 Val617Phe is suitable for routine laboratory application and helps the differential diagnosis of myeloproliferative syndrome. Althought the exact role of Val617Phe mutation testing has not yet been identified on the basis of a broad professional consensus, the testing is suggested in cases of erythrocytoses and thrombocytoses of unknown origin.


2018 ◽  
Vol 1 (2) ◽  
pp. 135
Author(s):  
Yudith Annisa Ayu Rezkitha ◽  
S. Ugroseno Yudho Bintoro ◽  
Ami Ashariati

Janus Kinase 2 (JAK2) plays an important role in mediating transduction signal of hematopoiesis, including in the pathogenesis of Myeloproliferative diseases (MPD). Various studies have been carried out to identify the position of aleles in tyrosine encoding mutations. Although the effect of JAK2 mutations is still not fully understood, the discovery of these mutations might be able to differentiate the types of polycythaemia vera, essential thrombocytemia, and primary myelofibrosis with malignant abnormalities. WHO has revised the MPD diagnosis criteria following this finding. This review will discuss the role of JAK2.


2013 ◽  
Vol 246 (4) ◽  
pp. 335-341 ◽  
Author(s):  
Zohreh Hosseinzadeh ◽  
Mentor Sopjani ◽  
Tatsiana Pakladok ◽  
Shefalee K. Bhavsar ◽  
Florian Lang
Keyword(s):  

2016 ◽  
Vol 91 (3) ◽  
pp. 441-447 ◽  
Author(s):  
A. Torraco ◽  
M. Bianchi ◽  
D. Verrigni ◽  
V. Gelmetti ◽  
L. Riley ◽  
...  

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