The low-incidence MNS antigens M(v), s(D), and Mit arise from single amino acid substitutions on GPB

J R Storry1, M E Reid, S MacLennan

  • 1New York Blood Center, New York, New York, USA. jstorry@nybc.org

Transfusion
|March 10, 2001
PubMed
Abstract

Insights

Genetic variations in the Glycophorin B (GPB) gene influence red blood cell antigen expression. Specific mutations at Thr3, Pro39, and Arg35 impact the S, s, and N antigens, affecting blood group phenotypes.

Area of Science:

  • Hematology
  • Molecular Biology
  • Genetics

Background:

  • The Glycophorin B (GPB) protein carries the 'N' antigen and expresses S and s antigens, with variations influenced by a polymorphism at amino acid position 29.
  • Low-incidence antigens M(v), s(D), and Mit are linked to reduced expression of S and/or s antigens.

Purpose of the Study:

  • To elucidate the molecular underpinnings of the M(v), s(D), and Mit low-incidence red blood cell antigens.
  • To define the genetic basis for weakened S and/or s antigen expression.

Main Methods:

  • Sequencing of the GPB gene (GYPB) using RT-PCR on RNA from patient samples.
  • Confirmation of identified point mutations through genomic DNA sequencing.

Main Results:

  • A 65C>G mutation in M(v)+ samples resulted in a Thr3Ser substitution.
  • A C>G mutation at nucleotide 173 in s(D)+ samples led to a Pro39Arg substitution.
  • A 161G>A substitution in Mit+ samples caused an Arg35His change, confirmed by serologic tests.

Conclusions:

  • Arg35 is crucial for the full expression of the S antigen.
  • Pro39 and Thr3 are unexpectedly vital for the complete expression of the s antigen.
  • Thr3 is essential for 'N' antigen expression, as M(v)+ red blood cells lack 'N'.