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Retired NBME 16 Answers

nbme16/Block 1/Question#41 (reveal difficulty score)
A 5-year-old boy with mental retardation is ...
Maternal origin of both chromosomes 15 ๐Ÿ” / ๐Ÿ“บ / ๐ŸŒณ / ๐Ÿ“–
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submitted by โˆ—cassdawg(1781)
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Prader-Willi syndrome occurs due to a defect in the paternal chromosome 15 which causes issue because of imprinting that occurs silencing the maternal chromosome. If there is not a functioning paternal allele, any maternal allele will be silenced leading to lack of a functional copy of the alleles and disease.

Imprinting is when certain alleles are expressed differently depending on which parent they are inherited from. Genes are silenced specific to either maternal or paternal origin, and therefore only one allele is expressed. If the NON-silenced gene is dysfunctional or absent, then there will not be expression of a functioning allele, and thus disease results.

The two primary disorders of imprinting are P rader-Willi (caused by dysfunctional Paternal chromosome 15) and Angel M an (caused by dysfunctional Maternal UBE3A on chromosome 15).

In this individual, he has Prader-Willi syndrome but does not have the customary deletion on the arm of chromosome 15. Remembering in Prader-Willi that the paternal chromosome is typically dysfunctional and the maternal genes are silenced, it can be assumed that in order to have the disorder he had two copies of the maternal chromosome and both were silenced, producing a functional deletion even though he does not have the actual deletion.

Another way of thinking of this is the genes that prevent Prader-Willi will always be silenced on maternal chromosomes, so even if he has normal maternal chromosomes he will have a lack of function and thus Prader-Willi syndrome unless he has a normal paternal chromosome.

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pakimd  just to add to this. this is an example of uniparental disomy +1



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