X-连锁严重联合免疫缺陷综合征家系IL2RG基因突变研究
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摘要
目的对3个临床拟诊X-连锁严重联合免疫缺陷综合征(X-SCID)患儿及父母进行基因突变分析,为遗传咨询及产前诊断提供依据。方法应用高通量测序和直接测序的方法对患儿及家系成员进行白细胞介素-2受体基因(IL2RG)突变检测,分析IL2RG基因外显子区及与外显子交界的部分内含子区域DNA序列改变情况,寻找可能的致病突变位点,并对其中一个家系进行羊水细胞产前诊断。结果家系1、家系2患儿IL2RG基因检测到c.202G>A(p.Glu68Lys)突变,家系3患儿IL2RG基因检测到c.676C>T(p.Arg226Cys)突变,患儿母亲均为相应突变携带者。家系3先证者母亲进行产前诊断胎儿为女性,携带与先证者相同的致病基因,夫妇双方选择继续妊娠。结论通过IL2RG基因检测明确诊断3例X-SCID患儿,并成功对1个X-SCID家系进行产前诊断,指导家系3夫妇选择妊娠。
Objective To analyze the gene mutations of three male children clinically diagnosed with X-linked severe combined deficiency syndrome(X-SCID), in order to provide evidence for genetic counseling and prenatal diagnosis. Methods Interleukin-2 receptor gene(IL2RG) mutation was detected by whole exome sequencing and direct sequencing in children and family members, and prenatal diagnosis was performed in one of the families. Results The mutation of c.202 G>A(p.Glu68 Lys)was detected in the IL2RG gene in family 1 and family 2,and the mutation of c.676 C > T(p.Arg226 Cys) was found in IL2RG gene of family 3.The mother of the proband found the fetus as female through prenatal diagnosis, carrying the same pathogenic gene with the proband, but this couple chose to continue the pregnancy. Conclusion Totally 3 cases of X-SCID are diagnosed by IL2RG gene detection, and successful prenatal diagnosis is given to one X-SCID family, thereby giving guidance for pregnancy of family 3.
Objective To analyze the gene mutations of three male children clinically diagnosed with X-linked severe combined deficiency syndrome(X-SCID), in order to provide evidence for genetic counseling and prenatal diagnosis. Methods Interleukin-2 receptor gene(IL2RG) mutation was detected by whole exome sequencing and direct sequencing in children and family members, and prenatal diagnosis was performed in one of the families. Results The mutation of c.202 G>A(p.Glu68 Lys)was detected in the IL2RG gene in family 1 and family 2,and the mutation of c.676 C > T(p.Arg226 Cys) was found in IL2RG gene of family 3.The mother of the proband found the fetus as female through prenatal diagnosis, carrying the same pathogenic gene with the proband, but this couple chose to continue the pregnancy. Conclusion Totally 3 cases of X-SCID are diagnosed by IL2RG gene detection, and successful prenatal diagnosis is given to one X-SCID family, thereby giving guidance for pregnancy of family 3.
引文
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[11] 刘钋宁,李虹,李强.白细胞介素-2受体共同γ链基因突变致X-连锁重症联合免疫缺陷病的临床分析[J].中华妇幼临床医学杂志:电子版,2014,10(3):70-74.
[12] 吴庆华,史惠蓉,刘宁,等.X-连锁严重联合免疫缺陷病一家系突变分析及产前诊断研究[J].中华儿科杂志,2012,50(12):851-854.
[13] 吴海涛,沈晓婷,江青剑,等.X连锁严重联合免疫缺陷病的植入前遗传学诊断[J].中山大学学报:医学科学版,2017,38(6):955-960.
[2] Fuchs S, Rensing-Ehl A, Erlacher M, et al.Patients with T /low NK IL-2 receptor γ chain deficiency have differentially-impaired cytokine signaling resulting in severe combined immunodeficiency[J].J Pediatr Hematol Oncol, 2014,44(10):3129-3140.
[3] Tan W, Yu S, Lei J, et al.A novel common gamma chain mutation in a Chinese family with X-linked severe combined immunodeficiency (X-SCID; T NK B+)[J].Immunogenetics,2015,67(11-12):629-639.
[4] Markiewicz S, Subtil A, Dautry-Varsat A, et al.Detection of three nonsense mutations and one missense mutation in the interleukin-2 receptor gamma chain gene in SCIDX1 that differently affect the mRNA processing[J].Genomics,1994,21(1):291-293.
[5] Pepper AE, Buckley RH, Small TN, et al.Two mutational hotspots in the interleukin-2 receptor gamma chain gene causing human X-linked severe combined immunodeficiency[J].Am J Hum Genet, 1995,57(3):564-571.
[6] Noguchi M,Yi H,Rosenblatt HM,et a1.Interleukin-2 receptor g chain mutation resuhs in X-linked severe combined immunodeficiency in humans[J].Cell,1993,73(1):147-157.
[7] Klatzmann D, Abbas AK.The promise of low-dose interleukin-2 therapy for autoimmune and inflammatory diseases[J].Nat Rev Immunol, 2015,15(5):283-294.
[8] Mou W, He J, Chen X, et al.A novel deletion mutation in IL2RG gene results in X-linked severe combined immunodeficiencywith an atypical phenotype[J].Immunogenetics,2017,69(1):29-38.
[9] Nourizadeh M, Shakerian L, Borte S, et al.Newborn screening using TREC/KREC assay for severe T and B cell lymphopenia in Iran[J].Scand J Immunol, 2018,26:e12699.
[10] 孔祥东,刘宁,徐学聚,等.IL2RG基因新突变致X-连锁重症联合免疫缺陷病二例及产前诊断研究[J].中华医学杂志,2014,94(16):1227-1231.
[11] 刘钋宁,李虹,李强.白细胞介素-2受体共同γ链基因突变致X-连锁重症联合免疫缺陷病的临床分析[J].中华妇幼临床医学杂志:电子版,2014,10(3):70-74.
[12] 吴庆华,史惠蓉,刘宁,等.X-连锁严重联合免疫缺陷病一家系突变分析及产前诊断研究[J].中华儿科杂志,2012,50(12):851-854.
[13] 吴海涛,沈晓婷,江青剑,等.X连锁严重联合免疫缺陷病的植入前遗传学诊断[J].中山大学学报:医学科学版,2017,38(6):955-960.