FUT1和 ABO双血型基因变异所致类孟买与A_(2)亚型血型献血者1例的遗传学分析并文献复习

Genetic analysis of a blood donor with combined FUT1 and ABO dual blood group gene variants resulting in para-Bombay and A 2 subtype blood types and a literature review

目的探讨1例FUT1和ABO双血型基因变异所致类孟买与A 2亚型血型无偿献血者的血型血清学特征和分子遗传学特征,并对携带FUT1*01W.37与FUT1*01W.23等位基因的类孟买血型相关文献进行复习。方法选择2023年8月于东莞市中心血站无偿献血,并且ABO血型鉴定正、反定型不一致的1例类孟买与A 2亚型血型献血者作为研究对象。采用血清学检测试验对献血者ABO血型、Lewis血型抗原及血清意外抗体进行鉴定。采用吸收放散试验对献血者血浆微量抗体和红细胞表面微量A、B、H抗原进行检测。采用Sanger测序法对其FUT1基因和ABO基因进行序列分析。分别以"类孟买""FUT1*01W.37""FUT1*01W.23"和"para-Bombay"为中、英文关键词,在中国知网数据库、万方数据知识服务平台及美国PubMed数据库中,检索携带FUT1*01W.37与FUT1*01W.23等位基因的类孟买血型受试者相关文献,并进行复习,检索时限设定为各数据库建库至2022年12月。本研究遵循的研究程序符合东莞市中心血站科研伦理委员会规定,并获得该伦理委员会批准(审批文号:2022005),并与献血者签署献血知情同意书。结果本研究献血者血清学检测结果显示其ABO血型鉴定存在正、反定型结果不一致,红细胞表面H抗原为阴性,Lewis血型为Le(a-b+)分泌型,血浆意外抗体为抗H同种抗体,判定献血者血型为疑似类孟买型。吸收放散试验结果显示献血者血型为疑似类孟买与A亚型血型。Sanger测序法显示,献血者FUT1基因型为FUT1*(c.35T+c.803A)/(c.35T+c.803A)纯合变异,FUT1*(c.35T+c.803A)等位基因双碱基变异在国际输血协会(ISBT)FUT1基因变异数据库中尚未见报道,该等位基因序列特征与ISBT数据库报道的FUT1*01W.37(c.803G>A)弱功能性等位基因接近;其ABO基因型为ABO*A2.05/O.01.02杂合变异。结合献血者血清学检测结果与基因检测结果,判定其血型为类孟买与A 2亚型血型。文献复习结果显示,根据本研究设定的文献检索策略,检索到1例携带FUT1*01W.37等位基因的青岛地区孕妇,其基因型为FUT1*01W.23/01W.37杂合子,2例携带FUT1*01W.23杂合等位基因受试者。结论本研究首次报道了1例类孟买血型和ABO亚型血型在同一个体中并存的献血者。根据献血者红细胞表面抗原特征,建议将FUT1*01W.37归类为FUT1无效等位基因。

Objective To investigate the serological and molecular genetic characteristics of a voluntary blood donor with combined FUT1 and ABO blood group gene variants causing para-Bombay and A2 subtype,and to review relevant literature on para-Bombay blood types carrying alleles such as FUT101W.37 and FUT101W.23.Methods A blood donor with para-Bombay and A 2 subtype who participated in voluntary blood donation at the Dongguan Blood Center in August 2023 was selected as the study subject.Serological tests were performed to identify the ABO blood group,Lewis blood group antigens,and unexpected serum antibodies in the donor.Adsorption-elution test was conducted to detect trace antibodies in the blood donor′s plasma to trace the A,B and H antigens on the red blood cell surface.Sanger sequencing was carried out to analyze the sequences of the FUT1 and ABO genes.Using keywords such as"para-Bombay""FUT1*01W.37"and"FUT1*01W.23"both in Chinese and English,relevant literature on para-Bombay blood type subjects carrying FUT1*01W.37 and FUT1*01W.23 alleles was retrieved from the CNKI,Wanfang Data Knowledge Service Platform,and PubMed databases,and the retrieval time was set as from the establishment of database to December 2022.This study has been approved by the Ethics Committee of Dongguan Blood Center(No.2022005),and informed consent of blood donation was obtained from the blood donor.Results Serological testing of the blood donor revealed inconsistent results between forward and reverse ABO blood typing,negative H antigen on the red blood cell surface,Le(a-b+)secretor type for Lewis blood group,and unexpected anti-H antibodies in the plasma,indicating a suspected para-Bombay type.Absorption-elution test suggested the blood type of the blood donor to be para-Bombay and A subtype.Sanger sequencing showed that the donor has harbored homozygous FUT1*(c.35T+c.803A)/(c.35T+c.803A)variant,with the FUT1*(c.35T+c.803A)allele containing a dual nucleotide variant unrecorded by the International Society of Blood Transfusion(ISBT)FUT1 gene variant database,which was similar to the weakly functional allele of FUT101W.37(c.803G>A)as recorded by the ISBT database.The ABO genotype was heterozygous ABOA2.05/O.01.02.Combining the results of serological and genetic testing,the blood type of the blood donor was determined to be para-Bombay and A 2 subtypes.Literature review has identified a pregnant women from Qingdao carrying the FUT1*01W.37 allele and 2 individuals carrying a heterozygous FUT1*01W.23 allele.Conclusion This study has discovered a blood donor with coexisting para-Bombay and ABO subtype blood groups.Based on the characteristics of red blood cell surface antigens,the FUT1*01W.37 as classified as an FUT1 null allele.