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Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):3132-6.

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

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1
Department of Pediatrics, Faculty of Medicine, Kyushu University, Fukuoka 810-8582, Japan. k-ihara@mailserver.med.kyushu-u.ac.jp

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.

PMID:
10077649
PMCID:
PMC15907
[Indexed for MEDLINE]
Free PMC Article
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