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Second, does repeat length variation contribute to the age of disease onset, the speed of disease progression, or even drive whether a patient will present with an ALS or FTLD phenotype?
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History does repeat itself.
History really does repeat itself.
What does repeated disappointment do?
This strongly suggests that repeat length does affect the degree of polymorphism for microsatellites.
In unaffected, non-expanded repeat carriers the repeat length does not exceed 24 units, while in patients the pathological expansions range from 700 to 4400 repeat units (86, 87).
Correlations between other demographic or clinical data with the CAG repeat length did not reveal significant results.
However, recent study on a large cohort of DM1 individuals showed that the estimated progenitor allele length was the major modifier of age-at-onset of the disease, accounting for 64% of the variation, without the threshold above which repeat length did not contribute toward age-at-onset [ 88].
The repeat length, however, does not influence the proportion of foci-positive nuclei.
This suggests the spatial resolution is due to abnormal development, as this reduced spatial resolution appears to be then be maintained over time, meaning it does not progressively worsen with aging, but does show a relationship with CGG repeat length.
For carrier 1, reprogramming did not seem to affect repeat length in line 6, as the band corresponding to the expanded allele has the same size as the band for fibroblasts.
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