Published online 16 July 2009
Haematologica, Vol 94, Issue 10, 1368-1374 doi:10.3324/haematol.2009.005918
Copyright © 2009 by Ferrata Storti Foundation
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Myeloproliferative Disorders

Evidence for a founder effect of the MPL-S505N mutation in eight Italian pedigrees with hereditary thrombocythemia

Kun Liu1, Maurizio Martini2, Bianca Rocca3, Christopher I. Amos4, Luciana Teofili2, Fiorina Giona5, Jianmin Ding6, Hirokazu Komatsu6, Luigi M. Larocca2, Radek C. Skoda1

1 Experimental Hematology, Department of Biomedicine, Basel University Hospital, Basel, Switzerland
2 The Departments of Hematology and Pathology, Catholic University, Rome, Italy
3 Department of Pharmacology, Catholic University School of Medicine, Rome, Italy
4 Department of Epidemiology, University of Texas M. D. Anderson Cancer Center, Houston, USA
5 Division of Hematology, Department of Cellular Biotechnologies and Hematology, "La Sapienza" University, Rome, Italy
6 Department of Medical Oncology and Immunology, Graduate School of Medical Sciences, Nagoya City University, Japan

Correspondence: Radek C. Skoda, MD, Department of Biomedicine, Experimental Hematology, University Hospital Basel, Hebelstrasse 20, 4031 Basel, Switzerland. E-mail:radek.skoda{at}unibas.ch

Background: Hereditary thrombocythemia is a rare disease characterized by increased megakaryopoiesis and overproduction of platelets. Germ line mutations have been identified in the genes for thrombopoietin (THPO) and its receptor, MPL. A clustering of familial cases with the MPL-G1073A mutation that results in a serine to asparagine substitution (S505N) has been recently reported in Italy. Here we performed haplotype analysis in nine families (eight Italian and one Japanese) with hereditary thrombocythemia carrying the MPL-S505N mutation in the MPL gene.

Design and Methods: The MPL gene was examined by genomic DNA sequencing. Haplotype analysis was performed using microsatellites and single nucleotide polymorphisms.

Results: Analysis of microsatellite markers and single nucleotide polymorphisms in the eight Italian families with hereditary thrombocythemia revealed the presence of a common haplotype compatible with a founder effect, which may have originated 23 generations ago. This haplotype was rarely observed in 132 unrelated individuals and was absent in a Japanese family with the MPL-S505N mutation.

Conclusions: The recurrent MPL-S505N mutation found in the eight Italian families with hereditary thrombocythemia is likely due to a founder effect.

Key words: hereditary thrombocythemia, MPL, mutation, founder effect, TPO.




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