国际输血及血液学杂志
國際輸血及血液學雜誌
국제수혈급혈액학잡지
INTERNATIONAL JOURNAL OF BLOOD TRANSFUSION AND HEMATOLOGY
2014年
5期
400-405
,共6页
黄小航%李本尚%罗长缨%王坚敏%罗成娟%丁丽霞%陈静
黃小航%李本尚%囉長纓%王堅敏%囉成娟%丁麗霞%陳靜
황소항%리본상%라장영%왕견민%라성연%정려하%진정
红细胞丙酮酸激酶缺乏症%突变,误义%造血干细胞移植
紅細胞丙酮痠激酶缺乏癥%突變,誤義%造血榦細胞移植
홍세포병동산격매결핍증%돌변,오의%조혈간세포이식
Pyruvate kinase deficiency of red cells%Mutation,missense%Hematopoietic stem cell transplantation
目的 通过对2例丙酮酸激酶缺乏症(PKD)患儿临床症状及PK-LR基因新突变类型的报道,探讨PKD的PK-LR基因诊断方法及行异基因造血干细胞移植(allo-HSCT)的疗效.方法 选择2009年2月及2013年8月,上海交通大学医学院附属上海儿童医学中心收治的2例PKD患儿作为研究对象.本研究遵循的程序符合上海交通大学医学院附属上海儿童医学中心人体试验委员会所制定的伦理学标准,得到该委员会批准,征得受试对象监护人的知情同意,并与之签署临床研究知情同意书.通过上海儿童医学中心检验科采集2例患儿的血液标本,采用Sanger基因测序及全外显子捕获测序对2例患儿PK-LR基因进行检测分析.采用allo-HSCT对2例患儿进行治疗,并分别对2例患儿进行随访.回顾性分析该2例患儿的临床症状、诊断方法及治疗方案.结果 ①2例PKD患儿丙酮酸激酶(PK)活性均降低,分别为8.00 IU/gHb与7.61 IU/gHb.②2例PKD患儿PK-LR基因检测分析共发现4种PK LR基因错义突变.其中,PK-LR基因c.941T＞C(p.Ile314Thr)突变已有文献报道,c.119G＞A(p.Arg40Gln),c.1015G＞A(p.Asp339Asn)及c.848T＞C(p.Va1283Ala)突变为PK-LR基因新的突变类型.4种突变的SIFT功能预测结果分别为0.20,0.37,0及0.23.③2例PKD患儿均接受allo-HSCT.患儿1于移植后第14天粒系及红系造血功能获得恢复,移植后第19天血小板(PLT)计数＞5×101 0/L,移植后第22天造血干细胞(HSC) 100％嵌合,患儿血型亦转换为供者血型.患儿2于移植后第12天粒系及红系造血功能获得恢复,移植后第19天PLT计数＞3×1010/L,移植后第18天HSC 100％嵌合,患儿血型亦转换为供者血型.④对2例PKD患儿分别随访5年和1年,患儿生存状况良好,造血系统及其他系统指标均为正常,获得成功治愈.结论 全外显子捕获基因测序方法可用于临床PKD基因诊断及PK-LR基因新型突变类型的发现;PK-LR基因新突变类型c.G119G＞A(p.Arg40Gln),c.1015G＞A(p.Asp339Asn)及c.848T＞C(p.Va1283Ala)亦可导致PKD的发生;allo-HSCT治疗本研究中2例PKD患儿是有效、可行的.
目的 通過對2例丙酮痠激酶缺乏癥(PKD)患兒臨床癥狀及PK-LR基因新突變類型的報道,探討PKD的PK-LR基因診斷方法及行異基因造血榦細胞移植(allo-HSCT)的療效.方法 選擇2009年2月及2013年8月,上海交通大學醫學院附屬上海兒童醫學中心收治的2例PKD患兒作為研究對象.本研究遵循的程序符閤上海交通大學醫學院附屬上海兒童醫學中心人體試驗委員會所製定的倫理學標準,得到該委員會批準,徵得受試對象鑑護人的知情同意,併與之籤署臨床研究知情同意書.通過上海兒童醫學中心檢驗科採集2例患兒的血液標本,採用Sanger基因測序及全外顯子捕穫測序對2例患兒PK-LR基因進行檢測分析.採用allo-HSCT對2例患兒進行治療,併分彆對2例患兒進行隨訪.迴顧性分析該2例患兒的臨床癥狀、診斷方法及治療方案.結果 ①2例PKD患兒丙酮痠激酶(PK)活性均降低,分彆為8.00 IU/gHb與7.61 IU/gHb.②2例PKD患兒PK-LR基因檢測分析共髮現4種PK LR基因錯義突變.其中,PK-LR基因c.941T＞C(p.Ile314Thr)突變已有文獻報道,c.119G＞A(p.Arg40Gln),c.1015G＞A(p.Asp339Asn)及c.848T＞C(p.Va1283Ala)突變為PK-LR基因新的突變類型.4種突變的SIFT功能預測結果分彆為0.20,0.37,0及0.23.③2例PKD患兒均接受allo-HSCT.患兒1于移植後第14天粒繫及紅繫造血功能穫得恢複,移植後第19天血小闆(PLT)計數＞5×101 0/L,移植後第22天造血榦細胞(HSC) 100％嵌閤,患兒血型亦轉換為供者血型.患兒2于移植後第12天粒繫及紅繫造血功能穫得恢複,移植後第19天PLT計數＞3×1010/L,移植後第18天HSC 100％嵌閤,患兒血型亦轉換為供者血型.④對2例PKD患兒分彆隨訪5年和1年,患兒生存狀況良好,造血繫統及其他繫統指標均為正常,穫得成功治愈.結論 全外顯子捕穫基因測序方法可用于臨床PKD基因診斷及PK-LR基因新型突變類型的髮現;PK-LR基因新突變類型c.G119G＞A(p.Arg40Gln),c.1015G＞A(p.Asp339Asn)及c.848T＞C(p.Va1283Ala)亦可導緻PKD的髮生;allo-HSCT治療本研究中2例PKD患兒是有效、可行的.
목적 통과대2례병동산격매결핍증(PKD)환인림상증상급PK-LR기인신돌변류형적보도,탐토PKD적PK-LR기인진단방법급행이기인조혈간세포이식(allo-HSCT)적료효.방법 선택2009년2월급2013년8월,상해교통대학의학원부속상해인동의학중심수치적2례PKD환인작위연구대상.본연구준순적정서부합상해교통대학의학원부속상해인동의학중심인체시험위원회소제정적윤리학표준,득도해위원회비준,정득수시대상감호인적지정동의,병여지첨서림상연구지정동의서.통과상해인동의학중심검험과채집2례환인적혈액표본,채용Sanger기인측서급전외현자포획측서대2례환인PK-LR기인진행검측분석.채용allo-HSCT대2례환인진행치료,병분별대2례환인진행수방.회고성분석해2례환인적림상증상、진단방법급치료방안.결과 ①2례PKD환인병동산격매(PK)활성균강저,분별위8.00 IU/gHb여7.61 IU/gHb.②2례PKD환인PK-LR기인검측분석공발현4충PK LR기인착의돌변.기중,PK-LR기인c.941T＞C(p.Ile314Thr)돌변이유문헌보도,c.119G＞A(p.Arg40Gln),c.1015G＞A(p.Asp339Asn)급c.848T＞C(p.Va1283Ala)돌변위PK-LR기인신적돌변류형.4충돌변적SIFT공능예측결과분별위0.20,0.37,0급0.23.③2례PKD환인균접수allo-HSCT.환인1우이식후제14천립계급홍계조혈공능획득회복,이식후제19천혈소판(PLT)계수＞5×101 0/L,이식후제22천조혈간세포(HSC) 100％감합,환인혈형역전환위공자혈형.환인2우이식후제12천립계급홍계조혈공능획득회복,이식후제19천PLT계수＞3×1010/L,이식후제18천HSC 100％감합,환인혈형역전환위공자혈형.④대2례PKD환인분별수방5년화1년,환인생존상황량호,조혈계통급기타계통지표균위정상,획득성공치유.결론 전외현자포획기인측서방법가용우림상PKD기인진단급PK-LR기인신형돌변류형적발현;PK-LR기인신돌변류형c.G119G＞A(p.Arg40Gln),c.1015G＞A(p.Asp339Asn)급c.848T＞C(p.Va1283Ala)역가도치PKD적발생;allo-HSCT치료본연구중2례PKD환인시유효、가행적.
Objective To investigate PK-LR genetic diagnosis and hematopoietic stem cell transplantation (allo-HSCT) of pyruvate kinase deficiency (PKD) through clinical symptoms of two children with PKD and new types of PK-LR gene mutation report.Methods In February 2009 and August 2013,two children with PKD in Shanghai Children's Medical Center,Affiliated to Shanghai Jiao Tong University School of Medicine were collected into this study.The study protocol was approved by the Ethical Review Board of Investigation in Human at Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine.Informed consent was obtained from all participants' parents.The blood specimens from the two PKD children were collected.PK-LR gene analysis of two children were detected by Sanger sequencing and whole exon capture sepuencing.Two PKD children were treated by allo-HSCT,and their clinical symptoms,diagnosis and treatment were retrospectively analyzed.Results ① Pyruvate kinase (PK) activation of two PKD children were reduced to 8.00 IU/gHb and 7.61 IU/gHb respectively.② Four types of PK-LR gene missense mutation were found in gene detection of two children.PK-LR gene c.T941T＞C(p.Ile314Thr) mutation was reported formerly,and c.119G＞A (p.Arg40Gln),c.1015G＞A(p.Asp339Asn) and c.848T＞ C (p.Va1283Ala) mutations were new.SIFT function prediction results of the 4 mutations were 0.20,0.37,0 and 0.23 respectively.③ Two PKD children were treated by alloHSCT.After transplantation,myeloid and erythroid hematopoiesis of children 1 were recovered on the 14th day.Platelet (PLT) count was ＞5× 1010/L on the 19th day.Hematopoietic stem cell (HSC) was complete chimerism on the 22th day,and the blood type of children 1 was converted to donor's.After transplantation,myeloid and erythroid hematopoiesis of children 2 were recovered on the 12th day.PLT count was ＞3× 1010/L on the 19th day.HSC was complete chimerism on the 18th day,and the blood type of children 2 was converted to donor's.Conclusions The whole exon capture sequencing can be used in the clinical diagnosis of PKD and searching for new types of PK-LR gene mutation.PK-LR gene c.119 G＞A (p.Arg40Gln),c.1015G＞A(p.Asp339Asn) and c.848T＞C(p.Va1283Ala) missense mutations could also lead to PKD.allo-HSCT could be an effective treatment for PKD.
