Korean J Hematol 2006; 41(1):
Published online March 30, 2006
https://doi.org/10.5045/kjh.2006.41.1.16
© The Korean Society of Hematology
국훈, 남호송, 백희조, 김영옥, 엄광현, 기해진, 조덕, 신명근, 이제중, 김형준, 국현, 황태주
전남대학교 의과대학 소아과학교실, 진단검사의학교실, 내과학교실, 약리학교실, 전남대학교 의과학연구소
Background:
The autosomal dominant giant platelet syndromes (GPS), characterized by triads of giant platelets, thrombocytopenia, and Döhle-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/ՌL. 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.
Keywords MYH9 mutation, Giant platelet syndrome, Arg1944Ter, Lys373Asn
Korean J Hematol 2006; 41(1): 16-27
Published online March 30, 2006 https://doi.org/10.5045/kjh.2006.41.1.16
Copyright © The Korean Society of Hematology.
국훈, 남호송, 백희조, 김영옥, 엄광현, 기해진, 조덕, 신명근, 이제중, 김형준, 국현, 황태주
전남대학교 의과대학 소아과학교실, 진단검사의학교실, 내과학교실, 약리학교실, 전남대학교 의과학연구소
Hoon Kook, Ho Song Nam, Hee Jo Baek, Young Ok Kim, Gwang Hyeon Eom, Hae Jin Kee, Duck Cho, Myung, Geun Shin, Je Jung Lee, Hyeoung Joon Kim, Hyun Kook, Tai Ju Hwang
Departments of, Pediatrics, Laboratory Medicine, Internal Medicine and, Pharmacology, Chonnam National University Hwasun Hospital,
Medical Research Center for Gene Regulation, Chonnam National University Medical School, Gwangju, Korea
Background:
The autosomal dominant giant platelet syndromes (GPS), characterized by triads of giant platelets, thrombocytopenia, and Döhle-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/ՌL. 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.
Keywords: MYH9 mutation, Giant platelet syndrome, Arg1944Ter, Lys373Asn