Annoyed by a UWorld question

[DarkHorizon]

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This question describes Fragile X Syndrome and asks for the defect, I recall to have read it in first aid the words "chromosomal breakage" specifically. I choose that and I am wrong. Correct answer is methylation of FMR1 gene. I then think that perhaps Methylation of FMR1 gene leads to chromosomal breakage as mentioned by first aid, but no, Uworld says there's no chromosomal breakage at all, it's just narrowing which make the chromosome thin and it appears as "chromosomal breakage". I look it up in Goljan, can't find anything. Look up in first aid again, it states "associated with chromosomal breakage". Pretty annoying to honest.

 

[RapplixGmed]

You have the association wrong.

Fragile X is diagnosed in vitro by looking at chromasomal breakage. It is seen if their cells are cultured in a folate deficient medium. Chromosomal breakage is a diagnostic tool and not the mechanism of the pathology. This diagnostic technique is not even used anymore and is a relic of historical interest.

The mechanism of the pathology of fragile X (and any other nucleotide repeat disorder such as huntington's or fredrich's ataxia) is by messing with the epigenetics (usually hypermethylation) of some regulatory gene.

Sometimes the brevity of FA leads to misunderstandings like this. Hope that helps.

 

[DarkHorizon]

You have the association wrong.

Fragile X is diagnosed in vitro by looking at chromasomal breakage. It is seen if their cells are cultured in a folate deficient medium. Chromosomal breakage is a diagnostic tool and not the mechanism of the pathology. This diagnostic technique is not even used anymore and is a relic of historical interest.

The mechanism of the pathology of fragile X (and any other nucleotide repeat disorder such as huntington's or fredrich's ataxia) is by messing with the epigenetics (usually hypermethylation) of some regulatory gene.

Sometimes the brevity of FA leads to misunderstandings like this. Hope that helps.

awesome, thanks

 

[xlr8]

There's also a similar question for Huntington's. I don't know if they directly said most trinucleotide disorders have gene silencing from the repeats but they sure did hint at that.

 

[engineeredout]

There's also a similar question for Huntington's. I don't know if they directly said most trinucleotide disorders have gene silencing from the repeats but they sure did hint at that.

Yeah that definitely came up in Uworld. Something about Huntington and similar disorders having hypermethylation of multiple genes.

 

[ArcGurren]

Yeah that definitely came up in Uworld. Something about Huntington and similar disorders having hypermethylation of multiple genes.

The Huntingtin gene mutation is supposedly implicated in hypermethylation of histones, which in turn decreases the production of neurotrophic proteins required for brain growth.