PIPk血型系统中一例罕见P表型的分子遗传机制研究

Molecular basis for an individual with rare p phenotype in P1Pk blood group system

目的分析P1Pk血型系统中1例罕见P表型的分子遗传机制。方法采用血清学方法鉴定先证者及其5个容系成员红细胞血型抗原和血清中的抗体。PCR扩增编码P1Pk的a1，4半乳糖基转移酶基因（a1，4-galactosyltransferase，A4GALD编码区及侧翼非翻译区后进行测序分析，并通过克隆测序法鉴定先证者父母A4GALT基因单体型。结果血清学实验证实先证者为罕见的P表型，其血清中含有抗-Tja抗体，而家系成员为常见的P2表型。DNA测序显示，先证者的A4GALT基因编码区存在1026-1029insC纯合突变，该处C碱基的插入可引起多肽链的移码突变，导致变异型a1，4半乳糖基转移酶比野生型多92个氨基酸残基；而其他家系成员在A4GALT基因该位点均为杂合性插入或野生型。结论在中国人群中发现因A4GALT基因1026-1029insC导致的P表型，该表型携带有抗-Tja抗体。

Objective To explore the molecular basis for an individual with rare p phenotype in the PIPk blood group system. Methods Erythrocyte blood group antigens and antibodies in serum were identified in the proband and five family members with a serological method. Coding regions and flanking untranslated regions of the al, 4-galactosyltransferase gene （A4GALT）encoding P1Pk antigens were amplified with polymerase chain reaction and directly sequenced. The haplotypes of A4GALT in the parents of the proband were also analyzed by cloning sequencing. Results The proband was found with a rare p phenotype with anti-Tja antibody in his serum by serological method. The other family members all had a common P2 phen0type. The results of DNA sequencing showed that a cytosine was inserted at nucleotide position 1026 to 1029 （1026-1029insC） of both alleles of the A4GALT gene in the proband. The mutation has caused a reading frame shift and formed a mutant protein by extending 92 amino acid residues. The other family members were either heterozygous for the insertion or of the wild type at above position. Conclusion The 1026-1029insc mutation of the A4GALT gene is probably responsible for the p phenotype identified for the first time in Chinese population, The individual with the p phenotype possesses anti-Tja antibody.