Genetic analysis of an individual with A 3 phenotype due to variant of A-glycosyltransferase enzyme gene
10.3760/cma.j.cn511374-20230414-00211
- VernacularTitle:A糖基转移酶基因变异所致A 3表型1例的遗传学分析
- Author:
Minxi LI
1
;
Xu ZHANG
;
Hua FAN
Author Information
1. 中国医科大学附属第四医院血液科，沈阳 110032
- Keywords:
A 3 phenotype;
α-1, 3-N-acetylgalactosaminyltransferase;
Molecular mechanism;
Bioinformatics analysis
- From:
Chinese Journal of Medical Genetics
2024;41(7):862-865
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the serological characteristics and molecular mechanism underlying an individual with A 3 phenotype. Methods:A 27-year-old ethnic Han Chinese woman presented at the Fourth Affiliated Hospital of China Medical University on May 12, 2022 was selected as the study subject. ABO blood type was determined with standard serological techniques. The ABO gene was subjected to direct sequencing of PCR products. Exons 6 and 7 of the ABO gene were sequenced using specific primers to determine the haplotypes. Bioinformatic software was used to analyze the structure of the mutant protein. Results:Serological typing of the ABO blood group has suggested a rare A 3 phenotype. The proband was found to harbor heterozygous c. 261delG, c. 467C>T and c. 745C>T variants by direct sequencing. Single strand sequencing revealed that she has harbored ABO* A3. 07and ABO* O. 01. 01 alleles. The ABO* A3. 07 allele has contained a c. 745C>T (p.R249W) variant on the background of an ABO* A1. 02 allele. The p. R249W substitution was predicted to be probably damaging by the PolyPhen2 software. The free energy change (ΔΔG) value predicted it to have a destabilizing effect on the GTA protein. Meanwhile, modeling of the 3D structure has predicted that the p. R249W amino acid substitution may alter the hydrogen bond network of the GTA protein. Conclusion:The p. R249W substitution of the α-1, 3-N-acetylgalactosaminyltransferase gene may reduce the antigen expression owing to a great destabilizing effect on the structure and function of the GTA protein.
