摘要
目的通过对1个罕见的A3亚型家系进行分子遗传学分析，探讨α-1，3-N-乙酰半乳糖胺转移酶基因突变对于A抗原表达的影响。方法采用血型血清学方法对先证者及家系成员进行ABO血型鉴定，应用PCR产物直接测序和基因克隆法对ABO基因的第6、7外显子进行序列分析以及单倍型分析。结果先证者红细胞包含弱A抗原，同时血清中含有抗-A和抗-B抗体。直接测序结果显示ABO基因第6外显子存在261delG突变，第7外显子存在467C〉T和745C〉T两个杂合位点。基因克隆序列分析得到两个等位基因A307和001。A307基因序列与A101基因比对在第467位碱基为C〉T突变和第745位碱基为C〉T，导致多肽链P156L和R249W替换。结论α-1，3半乳糖基转移酶基因467C〉T和745C〉T突变产生A307基因型，导致A抗原表达减弱。
Objective To explore the effect of α-1,3-N-acetylgalactosaminyltransferase gene variants on A antigen expression in a family where a member was suspected for a rare A3 subtype of the ABO variant. Methods Serological assay was carried out to determine the ABO blood group of the proband and his family members. To determine the haploid of the α-1, 3-N-acetylgalactosaminyltransferase gene of the proband, DNA was extracted and genotyped with sequence-specific primer PCR （PCR-SSP） followed by direct sequencing and cloning of exons 6 and 7 of the ABO locus. Results Weak A antigen was detected on red blood ceils of the proband, while anti-A and anti-B antibodies were detected in his serum. DNA sequencing showed a 261delG mutation in exon 6, and two heterozygote mutations （467 C〉T and 745C〉T） in exon 7 of the α-1,3-N-acetylgalactosaminyltransferase gene. Haplotype analysis has identified two alleles A307 and O01. Compared with the A101 allele, the A307 allele has harbored two nucleotides changes （467C 〉T and 745C〉T）, which resulted in substitution of two amino acids （P156L and R249W）. Conclusion The 467C〉T and 745C〉T mutations of the α-1,3-N-acetylgalactosaminyltransferase gene can result in an A307 phenotype with reduced expression of A antigen.
出处
《中华医学遗传学杂志》
CAS
CSCD
北大核心
2017年第4期602-605,共4页
Chinese Journal of Medical Genetics
基金
沈阳市科技计划项目（F-10-149-9-35,F10-206-1-00）
