Familial Essential Thrombocythemia Among Qatari Tribes
Authors: Yassin Mohamed A. , Al-Dewik Nader I , ElAyoubi Hanadi , Cassinat Bruno 
Published: October 2019

Essential thrombocythaemia (ET) is a chronic myeloproliferative syndrome due to sustained proliferation of megakaryocytes,which results in elevated numbers of circulating platelets, thrombotic or haemorrhagic episodes and occasional leukaemic transformation.Familial essential thrombocythemia,also called hereditary or inherited thrombocythemia or thrombocytosis, is a rare disorder transmitted in an autosomal dominant with clinical presentation and complications resembling sporadic essential thrombocythaemia (ET).Mutations in the thrombopoietin (TPO) gene causing overproduction of TPO and elevated TPO serum levels familial essential thrombocythemia is a heterogeneous disorder as families have been described with an activating mutation in the gene for the TPO receptor (c-MPL), the thrombopoietin gene, a germline mutation in JAK2 V617I or without a mutation in any of these genes

Occurrence of Essential thrombocythemia among arab population never been reported before. In this study, essential thrombocythemia is documented in 25 families from 5 major tribes in Qatar Familial cases were defined when two or more individuals within the same pedigree were affected with MPNs. Clinical records of affected relatives were reviewed systematically to confirm MPNs diagnosis. Patients without family history of were defined as having sporadic. MPNs Diagnosis of MPNs was made in accordance with the WHO criteria 2008

Ninety eight members of both sexes from 18  to 62 years of age in three successive generations. The propositus had a persistent elevation of the platelet count, splenomegaly, a normal hemoglobin level, a normal white blood cell count, and abnormal platelet aggregation. Platelet arachidonic acid metabolites assayed by high-performance liquid chromatography and serum thrombopoietin levels were normal. Megakaryocytes were increased in number and size. Both mature and early immature megakaryocytes, but no atypical megakaryocytes, were identified by surface immunofluorescence. Bone marrow cultures showed normal myeloid and erythroid colony formation, and chromosome studies revealed a normal  The analysis of mutations of JAK2 and MPL may improve our ability to identify these conditions. In a consecutive series of patients observed in our Institution from January 2011 to June 2013  total No of 300 MPNs patients were diagnosed, out of 300 patient, 119 had PV, 160 had ET, 15 had PMF and six patient had unclassified atypical MPN case. Out of 119 PV pts, 116 (97.4%) were positive for the JAK2 V617F mutation and 3 cases met the WHO criteria for PV but were negative for JAK2 V617F and JAK2 exon 12 mutations. Out of 160 ET pts, 80 (50%) were positive for JAK2 V617F, one had MPL S505N mutation and 79 cases met the WHO criteria for ET but were negative for both JAK2 617F and MPL mutations. Out of 15 PMF pts 5 (33.3%) were positive for JAK2 V617F and the unclassified case which was characterized by Deep Vein Thrombosis had JAK2 exon 13 mutation (R564L).

25 Arab families were described as having familial ET  (5 major tribes were screened )20  were having JAK2V617F  positive in three consequetive generations ,4 families were  having Familial ET in three generations but both Jak2v617F and MPL were negative

MPL S505N mutation  was found in one family( Father and daughter).there was no difference  in clinical presentation and response to therapy in sporadic versus familial cases.

Conclusion

In our series of familial cases clinical presentation, therapeutic approach  type and severity of complications were comparable to that of sporadic cases. Furthermore, the present study indicates the relevant possibility of familial MPNs, thus suggesting the opportunity of a detailed family history as part of the initial work-up of patients with MPNs; in addition it also suggests the usefulness of an accurate biological studies

Disclosures:

Yassin: qatar national research fund: Patents & Royalties, Research Funding. Al-Dewik:qatar national research fund: Patents & Royalties, Research Funding. Cassinat:qatar national research fund: Patents & Royalties, Research Funding.