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Analysis of the DNA of the Phenylalanine hydroxylase (PAH) gene in a patient with phenylketonuria revealed a mutation in the protein coding region whose predicted effect would be to replace the amino acid aspartic acid, with histidine. Nevertheless, no mutant protein could be found in the patient’s cells.How this could be as mutation is in the protein coding region,can anyone explain?

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  • $\begingroup$ Can the mutation be in an intron? Otherwise I assume that some kind of post-translation modification is involved. $\endgroup$
    – Alice
    Feb 24, 2014 at 12:23
  • $\begingroup$ Can you be a bit more specific about the mutation? $\endgroup$
    – Chris
    Feb 24, 2014 at 12:30
  • $\begingroup$ Please add more details.. When you mean DNA is mutated do you mean one allele or both.. $\endgroup$
    – WYSIWYG
    Feb 25, 2014 at 9:02

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In terms of the way that the question is worded, I imagine the most likely answer would be that the amino acid substitution D > H disrupts the folding of the protein so that it is recognised as being aberrant and is rapidly degraded.

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There are many possible reasons for this, the two most obvious ones are:

  1. Alternative splicing. Perhaps the mutation is indeed in the coding region but of an exon that is not constitutively expressed. As a result, the majority of transcripts created from this gene would not contain the mutation and neither would their resulting protein.

  2. Post translational modifications. Proteins with the mutation might actually be produced but the histidine is changed to an aspartic acid by post translational modification so the mutation is not detectable in the cell's proteins.

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