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Discussion Starter · #1 ·
Hello all... So there's this UWorld question which asks - and I'm paraphrasing here after analyzing the question to get the diagnosis - what is the mechanism of the symptoms in Fragile X syndrome... So I, having done First Aid, argue - oh - many CGG repeats make the chromosome "fragile" and, as it says in FA 2010 (Associated with chromosome breakage - p87) I choose the "DNA damage" or whatever option there was similar to that. Wrong!!!! Apparently the answer is DNA Methylation. FA's comment on this on the same block is "X-linked defect affecting the methylation and expression of the FMR-1 gene" I wish I could extrapolate from that somehow that what FA meant was ohh - yeah if there are a lot of cysteine (from the extra CGG) residues then they get methylated and then this methylation inactivates the whole FMR gene so no transcription occurs so you get the symptoms. That my friends, is how Fragile X works... I am soo going to fail...
 

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this is what HY GENETICS has to say!!!

fragile X is an X-linked recessive disorder caused by a 200-1000 + unstable repeat sequences of CGG outside the FMR1 gene on chromosome X for FMRProtein1, which is a nucleocytoplasmic shuttling protein binding several MRNAs found abunduntly in neurons. the 200-1000+ unstable repeat sequences of CGG creates a fragile site. this has also been associated with hypermethylation of FMR1 gene so that FMRP1 is not xpressed.

moreover it says that that there are 2 sites A which involves a 200-100+ unstable repeat sequence of CGG located in 5' untranslated region in FMR and site B that involves 200+ repeat sequences on FMR gene
 

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Btw, also in Huntington disease, the mechanism of damage is hypermethylation.

UW mentions that hypermethylation causes a so-called transcriptional silencing by hiding the DNA from the transcription factors.

Acetylation, on the other hand, exposes the DNA further, leading to the opposite; more transcription.
 

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Discussion Starter · #6 ·
Thanks DoctorF and Haisook. Questions like this are more fundamental than just memorizing a fact since it is more a detail about a concept. It scares me that after all this time I'm still having trouble with concepts...
 

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Thanks DoctorF and Haisook. Questions like this are more fundamental than just memorizing a fact since it is more a detail about a concept. It scares me that after all this time I'm still having trouble with concepts...
It seems we'll never stop learning until the last minute :eek:
 
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