A founder mutation in the MPL gene causes congenital amegakaryocytic thrombocytopenia (CAMT) in the Ashkenazi Jewish population.

Abstract

Congenital amegakaryocytic thrombocytopenia (MIM #604498) (CAMT) is a rare inherited disease presenting as severe thrombocytopenia in infancy. Untreated, many CAMT patients develop aplastic anemia within the first decade of life; the only effective treatment of CAMT is bone marrow transplantation. CAMT is the result of the presence of homozygous or compound heterozygous mutations in the thrombopoietin receptor-encoding gene, MPL. We report here the identification and characterization of a founder mutation in MPL in the Ashkenazi Jewish (AJ) population. This mutation, termed c.79+2T>A, is a T to A transversion in the invariant second base of the intron 1 donor splice site. Analysis of a random sample of 2018 individuals of AJ descent revealed a carrier frequency of approximately 1 in 75. Genotyping of six loci adjacent to the MPL gene in the proband and in the 27 individuals identified as carriers of the c.79+2T>A mutation revealed that the presence of this mutation in the AJ population is due to a single founder. The observed carrier frequency predicts an incidence of CAMT in the AJ population of approximately 1 in 22,500 pregnancies. The identification of this mutation will enable population carrier testing and will facilitate the identification and treatment of individuals homozygous for this mutation.

• Authors: Chaim Jalas, Sylvia L Anderson, Tova Laufer, Kristina Martimucci, Alex Bulanov, Xie Xie, Josef Ekstein, Berish Y Rubin
• Journal: Blood cells, molecules & diseases (Blood Cells Mol Dis) Vol. 47 Issue 1 Pg. 79-83 (Jun 15 2011) ISSN: 1096-0961 [Electronic] United States
• PMID: 21489838 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Receptors, Thrombopoietin
• MPL protein, human

Topics

• Alleles
• Base Sequence
• Congenital Bone Marrow Failure Syndromes
• Founder Effect
• Haplotypes
• Heterozygote
• Humans
• Infant, Newborn
• Jews (genetics)
• Male
• Mutation (genetics)
• Receptors, Thrombopoietin (genetics)
• Thrombocytopenia (genetics)