DAR/Cdes question

[Matthew Kim]

Hello. I've tried to come up with an answer over and over, but I've failed so far.

Can I ask a question here?

Our patient was identified to harbor DAR/Cde^s (compound heterozygote) in our commercial kit.

His Rh phenotype is D^wce. (c,e antigens are strongly positive) 

If his Cde^s (RHD-CE(3-7)-D) allele is true, the patient's phenotype should Cce^s. But why ce?

I am looking at blood group antigen factsbook and other papers, but I cannot find an answer.

Any help would be appreciated.

Edited February 10, 2018 by Matthew Kim

[Malcolm Needs ☆]

Big rugby day here in the UK - and will be again tomorrow, but, after that, I will TRY to answer your question, but it is not an easy question to answer!

[Malcolm Needs ☆]

I am a little confused by your question, in as much as, in one place you say that the patient has the Partial D Type DAR, but in another you say that the patient has the D^w antigen, sometimes known by its trivial name Weil, or more properly as Rh23, which is a low prevalence antigen associated with Partial DV Type 4.  I think you mean that your patient has the DAR D Type, and that the D antigen is typing weakly.  Am I correct in thinking this?  I hope so, otherwise it doesn't make sense (at least, to me).

Turning to the Cde^S type, there are several (at least 8) of these in terms of genetic background.  All have one thing in common, and that is a Leucine to Valine substitution at position 245 of the mature position, due to a point mutation in exon 5 of the RHCcEe gene.  Five of these also have the Tryptophan to Cysteine substitution at position 16, resulting in the expression of (normally) the C antigen, due to a point mutation in exon 1.  However, 74% of C-, c+ Black Americans with normal expression of c have Cysteine at position 16.

The thing is though, that any C antigen that is expressed is weakened, and some anti-C reagents do not react with it.  On the other hand, because there are at least 4 amino acid residues that are involved in the expression of the C and/or c antigen (at positions 16, 60, 68 and 120), it is more than possible (in fact, probable) where mutations are present, that the c antigen is expressed at a normal strength, whilst the C antigen is also expressed in the weakened form.  Indeed, the C antigen itself is a Partial C antigen, and such an individual can produce a form of anti-C, rather in the same way that an individual with a Partial D can produce a form of anti-D.

So, to cut a long story short, this is why the individual will express the c and e antigens in the cis position, even though they also express the C and e antigens (in a manner of speaking) in the cis position, and why the ce (compound) antigen can also be expressed.

[Matthew Kim]

Wow. Now I understand the cause of C-negative phenotype.

Malcolm, I am sorry for my mistake about D^w. I meant that the patient has the weak D phenotype. 

However, there is one thing I cannot fully understand.

Cde^S type has (RHD-CE(3-7)-D) on his RHD gene capable of causing altered C antigen.

You previously mentioned that Trp16Cys is a source of weakened C antigen expression. 

Do you think that both mutated RHD and RHCE genes affect altered C antigen expression?

Thank you for such a great answer.

 

 

 

Edited February 12, 2018 by Matthew Kim

[Malcolm Needs ☆]

I should warn you that I am no molecular biologist - all I know is what I have adsorbed from reading and from some of my friends and colleagues who are accomplished molecular biologists - but I am absolutely certain that both the mutated RHD and RHCE genes contribute to the weak expression of the C antigen, as you seem to suggest.

[Matthew Kim]

Thank you very much.

Now I understand why.

Your comment helps me a lot.