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Retired NBME Free 120 Answers

free120/Block 3/Question#18 (reveal difficulty score)
A 23-year-old woman comes to the physician ...
The patient's DMD carrier status is uncertain because of random X inactivation ๐Ÿ” / ๐Ÿ“บ / ๐ŸŒณ / ๐Ÿ“–
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submitted by โˆ—bwdc(697)
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DMD is X-linked. We know her mom is a carrier based on family history, supported by lab testing. But her mom has 2 X chromosomes, only one of which is mutated. There is no way to know which her daughter eventually receives and expresses by her phenotype (i.e if she is a carrier or not). Just because her CK is normal doesnโ€™t mean she isnโ€™t a carrierโ€“the phenotype of the X-linked carrier depends on X-inactivation.

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em_goldman  Is X-inactivation not randomly mosaic throughout tissues? My thinking is that random, evenly-distributed X activation would cause about ~half symptoms (ex Rett syndrome, X-linked dominant fatal in utero in males but survivable in females due to X-inactivation.) So you see her mom with (presumed) isolated increased CK, which you would expect in her if she was also a carrier. Maybe penetration is variable so you'd need genetic testing to confirm for sure -> the reason she doesn't have symptoms is x-inactivation. +3



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submitted by โˆ—claptain(25)
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I don't understand this question. They equate carrier-status to mean affected by the allele. We know her mother is a carrier because she has elevated CK. That means the patient has a 50% chance to be a carrier since she's female. Random X-inactivation doesn't matter when talking about carrier status because both alleles have a chance to get passed on. Random X inactivation is only important for determining whether she will develop symptoms.

I guess this is why the question was thrown out? Unless I'm missing something.

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claptain  Nvm, this question played me. I realize that E is the only possible choice. Both A and B would be 25% chances, not 50% chances, and you cannot assume whether she is or is not a carrier without genetic analysis (choices C and D). That leaves only E. +6
beansbeansbeans  Wait I agree with your first comment, can you explain what made you change your mind and understand this? +
yerpderp  They are referring to x inactivation in the daughter which would mean she could be a carrier but we cant tell. +1
cbreland  so her mom is a carrier because she doesn't have complete symptoms like the brother and uncle?? I guess I thought it was all of nothing with duchenne +
cbreland  Damn, her mom is 50. Duchenne patients don't live that long... nvm dumb on my part, should have made the connection +
j44n  her mom cant have the full blown disease because its an XLR disease. I think we had to narrow this down by process of elimination +



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submitted by rohan225(1)
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Why is the answer carrier status unknown? Why can't the mother be homozygous? Duchennes is X linked recessive.

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dkhan123  not sure but here is my logic: -Male sibling of patient has died from Duchenne, confirming mother MUST BE either affected or a carrier. -Mother does NOT have the Duchenne phenotype, but has elevated enzymes, suggesting she is a carrier. The Duchenne average life expectancy is 26. Also the question is written such that it implies the mother does not have the Duchenne phenotype and the elevated enzyme level is due to the carrier status of Duchenne and not an unrelated illness. -Lastly, the daughter has normal enzyme levels. This could be due to two possible scenarios, either she inherited the Duchenne gene and has inactivated it, or she never inherited the gene to begin with. +5



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submitted by โˆ—netsirk2023(1)
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This probably has to do with Barr Bodies (FA 2021, pg 61). To paraphrase FA, penetrance and severity of diseases in XX individuals can be impacted. DMD is included in their list.

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submitted by โˆ—madamestep(17)
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Her mom has high CK because her X inactivation is likely imbalanced to have more mutated X expressed. But note that a high CK does not equal full-blown Duchennes. It's similar to Hemophilia--women can have increased bleeding but not full hemophilia because of this phenomenon.

Her mother has some Duchenne phenotype, but we could just as easily see no phenotype in a carrier.

Further, if this woman is a carrier, her child has a 25% chance of developing DMD (50% chance of a boy, 50% of the bad X).

This woman likely has a 50% chance of being a carrier, she doesn't have DMD based on her CK and age and gender.

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