Missense mutations in the C-terminal portion of the B4GALNT2 -encoded glycosyltransferase underlying the Sd(a-) phenotype

Biochemistry and Biophysics Reports
Linn StenfeltMartin L Olsson

Abstract

Sda is a high-frequency carbohydrate histo-blood group antigen, GalNAcβ1-4(NeuAcα2-3)Galβ, implicated in pathogen invasion, cancer, xenotransplantation and transfusion medicine. Complete lack of this glycan epitope results in the Sd(a-) phenotype observed in 4% of individuals who may produce anti-Sda. A candidate gene (B4GALNT2), encoding a Sda-synthesizing β-1,4-N-acetylgalactosaminyltransferase (β4GalNAc-T2), was cloned in 2003 but the genetic basis of human Sda deficiency was never elucidated. Experimental and bioinformatic approaches were used to identify and characterize B4GALNT2 variants in nine Sd(a-) individuals. Homozygosity for rs7224888:T > C dominated the cohort (n = 6) and causes p.Cys466Arg, which targets a highly conserved residue located in the enzymatically active domain and is judged deleterious to β4GalNAc-T2. Its allele frequency was 0.10-0.12 in different cohorts. A Sd(a-) compound heterozygote combined rs7224888:T > C with a splice-site mutation, rs72835417:G > A, predicted to alter splicing and occurred at a frequency of 0.11-0.12. Another compound heterozygote had two rare nonsynonymous variants, rs148441237:A > G (p.Gln436Arg) and rs61743617:C > T (p.Arg523Trp), in trans. One sample displayed no differe...Continue Reading

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Datasets Mentioned

BETA
MK765047
MK765048
MK765049
MK797056

Methods Mentioned

BETA
genotyping
PCR
X-ray

Software Mentioned

SIFT
MODEL
SWISS
Ensembl
QuantStudio
Human splicing finder
R
NGL viewer
Protein BLAST
BLAST

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