罕见抗-JK3引起新生儿溶血病及家系Kidd血型基因研究

目的 研究Kidd系统稀有血型Jk(a-b-)产生抗-JK3引起的新生儿溶血病,Jk(a-b-)表型的分子机理及其家系Kidd血型的基因遗传.方法 对患儿血样做新生儿溶血病三项检测:直接抗人球蛋白试验、血清游离抗体和红细胞放散试验;患儿母血样做抗体鉴定及Kidd血型鉴定;患儿父血样做Kidd血型鉴定;采用PCR-SSP方法对患儿及其父母做Kidd血型的基因检测,并对Jk4-11外显子及其侧翼区域扩增后测序,分析其序列信息.结果 患儿为B型RhD阳性、Kidd表型为Jk(a-b+)、基因型为JKB/JKB (IVS5-1);患儿母为O型RhD阳性,Kidd表型为Jk(a-b-)、基因型为Jkb(IVS5-1)/JKb(IVS5-1);患儿父为B型RhD阳性,Kidd表型为Jk(a-b+)、基因型为Jkb3kb;患儿母血浆中存在抗-Jk3,患儿为抗-Jk3引起的新生儿溶血病.结论 患儿母在Jkb等位基因第5内含子3'端保守区剪切结合位点处发生了G到A的突变,导致mRNA转录本中从第6外显子开始缺失,致其Kidd表型为Jk(a-b-),其因妊娠免疫产生了抗-JK3并导致患儿发生新生儿溶血病.

Unusual anti-JK3 causes hemolytic neonatal diseases and gene of Kidd blood group study in their family memebers

Objective Pedigree analysis was conducted to reveal the genetic basis and serological features in a newborn with severe hemolytic disease caused by anti-Jk3 from the maternal plasma of an immunized Jk(a-b-) individual.Methods Kidd phenotyping and sequencing of SCL14Alwhole gene were performed to evaluate the Kidd blood group.Antibody identification and direct agglutinin test were conducted to detect anti-Jk3 in maternal and newborn plasma.The red blood cells of the newborn were also eluted using chloroform.Results The serological types according to ABO,RhD,and Kidd systems were B+ with Jk(a-b+) in the newborn and the father,and O+ with Jk(a-b-) in the mother.The Kidd alleles were Jkb/Jkb(IVS5-1) in the newbom,Jkb(IVS5-1)/JKb(IVS5-1) in the mother,and Jkb/Jkb in the father.Anti-Jk3 was detected in maternal and newborn plasma.The direct agglutinin test showed a positive result for newborn red blood cells and the extracted solution also showed the presence of anti-Jk3.Thus,severe hemolytic disease of the newborn caused by anti-Jk3 was confirmed.Conclusion The Jk(a-b-) phenotype is probably caused by a mutation at the splicing site of intron 5,which contributes to exon 6 mRNA deficiency and anti-Jk3 production after being immunized during pregnancy.