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I am reading a journal paper about a patient who has intellectual disability. The patient was found to have a balanced chromosomal translocation t(11;16)(q24.2;q24).

This chromosomal translocation disrupted two genes: CDH15 and KIRREL3. By using a genomic probe, the authors fine mapped the 16q24 translocation breakpoint to the second intron of CDH15. The chromosome 11 breakpoint junction sequence mapped to intron 1 of KIRREL3. Only one chromosomal copy of CDH15 and KIRREL3 were disrupted.

However, there is something about this paper that I don't fully understand. The authors state in the following:

We began by sequencing both copies of the CDH15 and KIRREL3 genes in the patient with the translocation. No alterations were identified, indicating that the t(11;16) translocation does not unmask a recessive mutation in either gene.

In the above, it seems that the authors are trying to identify whether there are any recessive mutations in the CDH15 and KIRREL3 genes. I have read online that a recessive mutation is one in which both alleles must be mutant in order for the mutant phenotype of be observed.

However, since the chromosomal translocation disrupted one of the alleles for both CDH15 and KIRREL3, wouldn't you need both alleles of the CDH15/KIRREL3 genes to be intact in order to successfully identify a recessive mutation?

Any insights are appreciated.

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You're reading too much into the authors statement.

The authors simply claim they have no evidence for any mutations in the working copies of the genes, and therefore not even preliminary evidence for a recessive mutation.

You're right that if they had found mutations in either gene, this wouldn't be sufficient evidence to conclude the translocation unmasks a hidden recessive mutation resulting in the given phenotype. But this is completely moot in this case anyway.

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    $\begingroup$ They actually claim they have some evidence for a lack of mutations in the non-disrupted copies of the genes, which is stronger than no evidence for any mutations. $\endgroup$
    – Armand
    Sep 16 at 14:05
  • $\begingroup$ Yes agreed - I'd missed that subtlety (or really thought about it at all before) $\endgroup$
    – Greg
    Sep 16 at 15:06
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Re:

I have read online that a recessive mutation is one in which both alleles must be mutant in order for the mutant phenotype of be observed.

Perhaps it's better to think of it as "all" rather than "both", as sometimes there are 3 or more alleles, and sometimes only one. When the authors write

does not unmask a recessive mutation in either gene

the unmasking refers to effective disruption of the translocation alleles, leaving only ("unmasking") one remaining non-disrupted allele in each of the two genes. If there were an obvious loss-of-function mutation in either of these alleles, that might be an explanation for the observed phenotype. They've checked to rule out this possibility.

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