CAJ | 학술논문

目的了解家族性骨髓增殖性肿瘤( MPN)患者及其家系成员中JAK2、c-mpl、EPOR、MPLW515 L/K、TET2基因是否存在异常,为深入探讨MPN发病机制提供依据.方法对2例先后在我院诊治的同胞MPN患者及其家系成员(共15人)进行血常规检查,对存在异常者进行骨髓相关检查,并应用PCR、DNA测序等方法明确有关基因的表达状况.结果 2例患者中先证者为原发性血小板增多症,其胞弟为真性红细胞增多症,其余成员均无相关临床表现.根据血常规及骨髓检查确诊了第3例(胞妹)MPN患者.PCR及测序结果显示3人存在JAK2V617F突变,其中先证者为纯合型,其胞弟和父亲为杂合型.所检查的家系成员均不存在bcr-abl融合基因及c-mpl、EPOR、MPLW515L/K和TET2基因突变.对该家族JAK2基因cDNA全长测序发现:2人存在G380A杂合型突变(127位甘氨酸变为天冬氨酸),13人存在C489T突变,14人存在G2490A突变,但后两者均为同义突变.结论 JAK2V617F是诊断MPN的重要指标之一,该家族中JAK2V617F突变涉及两代人.对于初发MPN患者,建议筛查其家族成员,从而尽可能对部分家族性MPN患者做到早期诊断.JAK2基因全长测序发现存在除JAK2V617F外的基因突变.
목적 료해가족성골수증식성종류( MPN)환자급기가계성원중JAK2、c-mpl、EPOR、MPLW515 L/K、TET2기인시부존재이상,위심입탐토MPN발병궤제제공의거.방법 대2례선후재아원진치적동포MPN환자급기가계성원(공15인)진행혈상규검사,대존재이상자진행골수상관검사,병응용PCR、DNA측서등방법명학유관기인적표체상황.결과 2례환자중선증자위원발성혈소판증다증,기포제위진성홍세포증다증,기여성원균무상관림상표현.근거혈상규급골수검사학진료제3례(포매)MPN환자.PCR급측서결과현시3인존재JAK2V617F돌변,기중선증자위순합형,기포제화부친위잡합형.소검사적가계성원균불존재bcr-abl융합기인급c-mpl、EPOR、MPLW515L/K화TET2기인돌변.대해가족JAK2기인cDNA전장측서발현:2인존재G380A잡합형돌변(127위감안산변위천동안산),13인존재C489T돌변,14인존재G2490A돌변,단후량자균위동의돌변.결론 JAK2V617F시진단MPN적중요지표지일,해가족중JAK2V617F돌변섭급량대인.대우초발MPN환자,건의사사기가족성원,종이진가능대부분가족성MPN환자주도조기진단.JAK2기인전장측서발현존재제JAK2V617F외적기인돌변.
Objective To comprehend the abnormalities of JAK2,c-mp,EPOR,MPW515L/K and TET2 genes in patients with familial myeoproliferative neoplasm (MPN) and their relatives,and to explore mechanism of MPN pathogenesis.Methods The complete blood counts of 2 brothers diagnosed with MPN in out hospital and their family members (15 persons in together) were performed,and bone marrow(BM) examinations in patients with abnormal blood count were performed PCR,DNA sequencing were used to evaluate the expression of related genes.Results The elder brother was diagnosed with essential thrombocythemia (ET),the younger one was polycythemia vera (PV),and others had no clinical manifestation.The third MPN patient was diagnosed based on the blood count and BM examination.The PCR and sequencing results showed that there was JAK2V617F mutation in 3 patients,the elder brother was homozygous,the younger and their father were heterozygous.There were no BCR/ABL fusion gene and c-mp,EPOR,MPW515L/K,TET2 gene mutation in any member.By sequencing the full-length cDNA of familia JAK2 gene,we found that G380A heterozygous mutation was detected in 2 patients,which changed glycine at 127 into aspartic acid,C489T mutation was detected in 13 patients,G2490A mutation in 14,but both of them were synonymous mutations.Conclusions JAK2V617F is one of the important indicators to diagnose MPN.The JAK2V617F mutation of this family involves two generations.For newly diagnosed MPN patients,their family members should consider screening,so some familial patients can be diagnosed as early as possible.Gene mutation besides JAK2V627F canbe detected by sequencing the full-length of JAK2 gene.