PIGG defines the Emm blood group system

Area of Science:

• Genetics
• Immunology
• Hematology

Background:

• The Emm antigen is a high-incidence red cell antigen.
• Anti-Emm antibodies can cause severe hemolytic transfusion reactions.
• The genetic basis and antigenic epitope of Emm have remained elusive.

Observation:

• Whole genome sequencing in Emm probands identified mutations in the PIGG gene.
• PIGG encodes GPI-ethanolaminephosphate transferase II, essential for GPI anchor biosynthesis.
• Multiple PIGG mutations were found in unrelated Emm individuals.

Findings:

• A homozygous 2-bp deletion in PIGG (c.2624_2625delTA) was identified in Emm brothers.
• This PIGG mutation leads to a frameshift and premature stop codon.
• The Emm phenotype is associated with PIGG deficiency, impacting GPI anchor formation.

Implications:

• This suggests a potential new Emm blood group system based on ethanolamine phosphate (EtNP) in GPI anchors.
• The findings explain naturally occurring anti-Emm antibodies.
• Further research is needed to explore potential neurologic associations.