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Novel DNA mutation in alpha 2 gene predicting cd77Pro>Leu

Last post 07-29-2008, 14:13 by Joanne. 2 replies.
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  •  07-25-2008, 12:30 587

    Novel DNA mutation in alpha 2 gene predicting cd77Pro>Leu

    We have a couple with a 10 week pregnancy in whom we found the following :
     
    Female:DNA analysis = CCC> CTC IN CD77 of the alpha 2 globin gene
    Female hematology: Hb 13.3g/dl; Hct 41; MCV 78.3fL; MCH 25.4 pg; HbA 2 3.1%; HbF 1%.
     
    Male: DNA analysis = Alpha zero Mediterranean deletion heterozygote.
     
    No other alpha ort beta globin gene mutations associated with alpha ot beta thalassemia in Greece were observed.
     
    To offer genetic counselling we would like everyone's opinion on the phenotype of a compound heterozygote; it is likely that the variant levels would be at least 50% with the alpha zero deletion in trans. 
    What is the consequence of the amino acid change Pro>Leu at codon 77 (alpha77(EF6)Pro>Leu) 
    A compound heterozygote would likely have HbH disease-like condition, but would it be a severe form to justify prenatal diagnosis and pregnancy termintation?????
     
    Can I please have comments on the above as soon as possible from anyone who may have some relevant experience!
     
    Many thanks in anticipation,
     
    Emmanuel Kanavakis and Joanne Traeger-Synodinos,
    Laboratory of Medical Genetics,
  •  07-28-2008, 18:29 588 in reply to 587

    Re: Novel DNA mutation in alpha 2 gene predicting cd77Pro>Leu

    Hi Jan,

     Cannot reaally offer any advice from relevant experience as we have not encountered this variant in the UK. However we have a patient with Hb Toulon, a1 77 CCC>CAC, Pro>His, who had normal red cell indices. How sure are you that the reduced MCH is associated with the variant? Is it unstable? If not, I would say that it would not result in severe Hb H disease in combination with alpha zero thalassaemia.

    John

  •  07-29-2008, 14:13 589 in reply to 588

    Re: Novel DNA mutation in alpha 2 gene predicting cd77Pro>Leu

    Thanks John; Henri Wajcman is of the same opinion.

    Jan

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