Clinical Characteristics of Autosomal Dominant Giant Platelet Syndromes and Mutation Analysis of MYH9

BACKGROUND: The autosomal dominant giant platelet syndromes (GPS), characterized by triads of giant platelets, thrombocytopenia, and Dohle-like leukocyte inclusions are caused by MYH9 mutation, a gene encoding the nonmuscle myosin heavy chain-IIA. This study was aimed to identify the Korean GPS patients and to define clinical findings and molecular characteristics on them. METHODS: After taking a family history, platelets were counted using hematologic autoanalyzer and peripheral blood smear (PBS) was examined for platelet size and number, and the presence of leukocyte inclusions. Mutation of MYH9 was studied from mononuclear cells from PB by direct sequencing of previously known 8 exons after PCR amplification of genomic DNA. RESULTS: Twenty patients from 5 unrelated families were diagnosed as GPS. Giant platelets, greater than red cells on PBS, were found to be 3.1% of platelet (range, 1~11%). The median platelet count was 61,000/microliter. Inclusion bodies were found in 3 families. Two families had previously reported mutations. Family I had Arg1944Ter in exon 40, located in the tail portion of myosin, while Family IV had Lys373Asn in exon 10, located in the proximal portion of myosin head. The mutations were found only in affected patients, but not in normal siblings or unrelated families. CONCLUSION: In this study, we identified several families with autosomal dominant GPS. Two families had known MYH9 mutations, Arg1944Ter and Lys373Asn. The search for unknown mutations in the remaining families as well as study of protein structural and functional alteration seems to be necessary for further delineation of these rare genetic disorders.

Giant platelet syndrome / 소아과

Giant platelet syndrome is a group of unique disorders characterized by the presence of abnormally large platelets, and usually accompanied by thrombocytopenia. Most cases of giant platelets are encountered in idiopathic thrombocytopenic purpura(ITP). In contrast, inherited giant platelet disorders, a group of heterogeneous diseases, are rare. Bernard-Soulier syndrome and its variants, and MYH9 related diseases have been defined at the molecular level. Abnormalities in transcription factors are implicated in a couple of macrothrombocytopenia syndromes. However, the molecular defects are unknown in gray platelet syndrome. It is important to make a proper diagnosis of congenital macrothrombocytopenia to avoid unnecessary medications and potentially dangerous treatment for presumed ITP.