Identification of mutations in the c-mpl gene in congenital amegakaryocytic thrombocytopenia

Kenji Ihara, Eiichi Ishii, Mariko Eguchi, Hidetoshi Takada, Aiko Suminoe, Robert A. Good, Toshiro Hara

Research output: Contribution to journalArticlepeer-review

205 Citations (Scopus)

Abstract

Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare disorder expressed in infancy and characterized by isolated thrombocytopenia and megakaryocytopenia with no physical anomalies. Our previous hematological analysis indicated similarities between human CAMT and murine c-mpl (thrombopoietin receptor) deficiency. Because the c-mpl gene was considered as one of the candidate genes for this disorder, we analyzed the genomic sequence of the c-mpl gene of a 10-year-old Japanese girl with CAMT. We detected two heterozygous point mutations: a C-to-T transition at the cDNA nucleotide position 556 (Q186X) in exon 4 and a single nucleotide deletion of thymine at position 1,499 (1,499 delT) in exon 10. Both mutations were predicted to result in a prematurely terminated c-Mpl protein, which, if translated, lacks all intracellular domains essential for signal transduction. Each of the mutations was segregated from the patient's parents. Accordingly, the patient was a compound heterozygote for two mutations of the c-mpl gene, each derived from one of the parents. The present study suggests that at least a certain type of CAMT is caused by the c-mpl mutation, which disrupts the function of thrombopoietin receptor.

Original languageEnglish
Pages (from-to)3132-3136
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number6
DOIs
Publication statusPublished - Mar 16 1999

All Science Journal Classification (ASJC) codes

  • General

Fingerprint

Dive into the research topics of 'Identification of mutations in the c-mpl gene in congenital amegakaryocytic thrombocytopenia'. Together they form a unique fingerprint.

Cite this