chemamr
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Definitively itīs an X linked DOMINANT trinucleotide repeat expansion disorder. 
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| mesh
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thanks a lot chemamr.....
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| chemamr
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youīre welcome !
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| hgheith
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I found in robbins that it's X linked recessive.
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| mesh
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i agree with u hgheith...even goljan says that....
but in kaplan its written X linked dominant.....
a bit confusion....... 
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| hgheith
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that is confusing! I would stick with robbins, it's more reliable, but I think the main thing about this disorder is the trinucleotide repeats. If anyone knows for sure I'd love to find out!
Also I have a pneumonic to help remember the repeat: CGG: "Congenital Giant Gonades"
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| Galaxum
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Hi all,
Thank hgheith for memonic CGG, I couldnot remember them before.
Dominant or regressive FX make us confused a lot.
Kaplan is Dominant (in Biochemistry, but nothing in Pathology). Goljan and Robbin precipitate at Recessive.
However, we can see in Robbin:
_ carrier male: unaffected fragile X male
_ 50% full mutation in one X female present disease (so this is not a typical recessive model, and can say dominat model with anticipation )
The bottom line is that is uncertain and that is the hell of mle we have to suffer.
Anyway I must tick recessive if forced to do.
Thanks for sharing thinking
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| ferekide
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x recessive for sure
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| chemamr
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yes, I had read it in kaplan, but itīs good to know about these other sources.
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| KrazyK
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I think looking at how one would classify whether it is X-linked dominant or X-linked recessive illustrates the difficulty in determining whether it is one or the other. In either XD or XR inheritance, males have only one allele and will be affected, so one needs to look at females. My understanding from Kaplan is that 50% of all females will be affected, and that this is due to X-inactivation of 1/2 of female cells. So to actually determine whether it is XR or XD on a cellular level, one would need to look at the very small % of female cells that are not inactivated.
Recall that there is a difference between saying something is AD or AR on a cellular or organismal level. (An example are Tumor Suppressor genes, like Rb. On a cellular level, they are AR since 2 mutations are required in any one cell to knock out the gene. However, on an organismal level (if you were to look at a pedigree), you would see an autosomal dominant inheritance pattern for inherited cancers resulting from TS genes since if one gene is knocked out in all cells by an inherited mutation for say Rb, there are so many cells and mitoses that it is almost inevitable that one of those cells that already has an inherited mutation in say the Rb gene will accumulate an acquired mutation during the course of an individuals lifetime, resulting in a cancer. Therefore, the cancer syndrome will be inherited in an AD fashion on an organismal level.)
For any X-linked mutation, whether it is XR or XD, X-inactivation will occur. For a condition that is truly X-linked recessive on an organismal level, having about 50% of the cells with inactivated mutated allels and thus 50% cells with a functioning normal allele is enough to prevent the condition from occurring. So there is a threshold % of cells with inactivated mutant alleles (= functioning nl alleles) - we'll call it P - above which the phenotype of the mutation is expressed. If P < 50% (say 30% or something), most women will have about 50% inactivated mutated allels, so the mutation will be X-recessive. If P>50%, most women will have less than X so the mutation will be X-linked dominant. This may furthermore be complicated by which tissues each of these genes is expressed in, etc. Also note the further P is from 50%, the more definitely a disease will be X-linked R or X-linked dominant, since fewer women will be likely to develop it. In fragile X, it is said about 50% of women with 1 mutation will develop phenotypic expression of the disease (Kaplan). This indicates that most women this P is most likely near 50%.
Semantically, one might call this an X-linked dominant disease with 50% penetrance, since it is possible to inherit it from parent to daughter and get clinical manifestations of the disease. (In a true X-linked recessive disease, the P (or percentage of cells with nl alleles after inactivation) will be low enough that the other parents intact copy will allow for a high enough % of cells expressing nl genes after inactivation to make up for it. How low this % has to be depends on the # of cells present at inactivation - if anyone wants to look that up. The more cells there are, the more likely any one female will have close to 50% of inactivated mutant alleles, so P does not need to be so low.
I'm wasting a lot of space and study time on this, but I guess it seems like there might be some more complicated reasons why the books are disagreeing than just a simple typo. The most important facts I guess have been stated by other ppl: CGG trinucleotide rpt dz, etc.
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