Cis AB


Cis AB is a type of rare mutation in the ABO gene. It happens when the transferase allele contains a mix of amino acids from either A or B alleles, producing a bifunctional enzyme that can produce both types of antigens, usually with one weaker than the other. This results in a serum test result much like the standard, separate AB phenotype, although the weaker antigen can occasionally fail to be detected. It complicates the basic inheritance pattern and blood-transfusion compatibility matching for ABO blood typing.
Different DNA mutations of either type A or Type B alleles change amino acids in enzyme transferase A or B, homologous enzymes differing in only four of 354 amino acids. A single change in ABO gene DNA could switch type B to type A and then, a new hybrid enzyme can produce both weak B and A2. The most common mutation is an A105 allele variation in exon 7 nucleotide position G803C changing glycine to alanine. Another 8 alleles are reported in BGMUT, most recently in China and Taiwan. Some Cis-AB carriers need components like washed red blood cells or autotransfusion of serum and blood.
Cis-AB type was studied first in humans in Japan and South Korea where this rare type is more common, although it is seen in a few European families. In the year 2004, the American Red Cross described a family in Nebraska with a father of type cis-AB negative, a mother type O and their baby of type cis-AB. Since then, several cases in the United States have been reported. Antigen expression is weaker than A1 or B.

Scenarios

When one parent carries a Cis AB allele, the other allele can be any of O, A or B. The phenotype of this parent is always AB, but the children will inherit either the AB or the other allele from this parent. They could alternatively not inherit either allele from them.
  1. If the other parent is O phenotype the three possible scenarios for the blood group of children of a Cis AB carrier are:
  2. # The second allele is O: children are either AB or O
  3. # Second allele is A: Children are either AB or A
  4. # Second allele is B: Children are either AB or B
  5. # A very rare 4th possibility exists: if the other allele is also Cis AB then the children will be always AB irrespective whatever the other parent is, because they will have one cis AB allele from this parent.
  6. If the other parent is type A, depending on whether this parent is genotypically AA or AO and what the other allele is in the Cis Ab carrying parent, the following scenarios are possible:
  7. # Other parent is AO and the second allele is O: The children are either AB or A or O
  8. # Other parent is AA and the second allele is O: The children are either AB or A
  9. # Other parent is AO and the second allele is A: The children are either AB or A
  10. # Other parent is AA and the second allele is A: The children are either AB or A
  11. # Other parent is AO and the second allele is B: The children are either AB or B
  12. # Other parent is AA and the second allele is B: The children are always AB
  13. # Rare situation: If the other allele is also cis AB: The children are always AB
  14. Likewise, similar scenarios for the other parent being type B are:
  15. # Other parent is BO and the second allele is O: The children are either AB or B or O
  16. # Other parent is BO and the second allele is A: The children are either AB or A
  17. # Other parent is BO and the second allele is B: The children are always AB or B
  18. # Other parent is BB and the second allele is B: The children are either AB or B
  19. # Other parent is BB and the second allele is O: The children are either AB or B
  20. # Other parent is BB and the second allele is A: The children are always AB
  21. # Rare situation: If the other allele is also cis AB: The children are always AB
ABO inheritance is generally derived assuming the children are not the rare Bombay phenotype, which would require both parents to be carriers of it.

Real life implications

Maternity and paternity disputes

When testing paternity or maternity by ABO blood group alone, it is possible to have a paradoxical result in the rare instance that a cis-AB genotype is involved. For example, a child of a cis AB individual and an O individual will be either AB or O instead of the usual A or B.

Differential diagnosis

If the child of an AB and an O individual is O, then a rare alternative possibility is that the parents were carriers for the Bombay phenotype and the child is a Bombay homozygous by genotype thus expressing Bombay phenotype also called Oh where, despite the presence of the ABO alleles, the substrate from which those antigens are made is not made and thus A, B and even O antigen are not expressed at all and are completely absent from the red cells.