Objective: To explore the potential molecular mechanism of Ax subtypes in Chinese population based on an Ax subtype family. Methods: The ABO blood group serological tests and detection of the total plasma activity of alpha α-1,3-N-acetylgalactosaminyltransferase were conducted. ABO gene was sequenced directly and sequenced after cloning to construct 3D molecular model, and then the effect of identified mutation on protein stability changes (ΔΔG) of alpha α-1,3-N-acetylgalactosaminyltransferase was predicted. Results: The proband was diagnosed as AxB subgroup byserological analysis, and AW.38/B.01 was identified by DNA analysis. His two daughters were identified as A and AB blood group, and their ABO genotypes were A1.02/B.01, A1.02/AW.38, respectively.There was a c.426G>C heterozygous mutation in ABO exon 7 of the proband and his A type daughter, leading to p.M142I change in the amino acid of α-1,3-N-acetylgalactosaminyltransferase. Molecular modeling and analysis suggested that the mutation may lead to changes in the number of hydrogen bonds formed. The increase of ΔΔG value of thermodynamic stability changes indicated that the protein stability was reduced. Conclusions: The mutation of p.M142I in α-1,3-N-acetylgalactosaminyltransferase may lead to Ax phenotype by reducing the stability of the enzyme. In vitro study is needed for further investigation.
WANG Dengfeng, CUI Wenyan, ZOU Wei, LI Fang, WANG Xuefeng, CAI Xiaohong
. Molecular mechanism of Ax subtype caused by p.M142I mutation in alpha 1-3-N-acetylgalactosaminyltransferase[J]. Journal of Diagnostics Concepts & Practice, 2018
, 17(03)
: 260
-265
.
DOI: 10.16150/j.1671-2870.2018.03.006
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