As DM1 patients are characterized by expanded CTG tracts, it is likely that the mechanistic basis for the pathology observed in this mouse strain differs in important ways from that observed in DM1 patients.
Fetal blood sampling (FBS) can be used in addition to CTG, but it is invasive and time consuming, and only provides time-limited information, all of which have limited its application on a wide scale [ 8].
The only in-frame methionine codon is located in the middle of the ORF, however the first codon of the longest ORF is CTG, so it is possible that this gene uses an alternative CUG start codon [ 26].
The SCA8 mutation involves two overlapping genes ATXN8OS and ATXN8 [ 67] with normal alleles of 15 to 50 CTG repeats; it is mainly characterized by cerebellar involvement with hyperactive tendon reflexes [ 77].
If used with a primer located downstream of the CTG repeat, it can be useful for detection of variant repeats located at the 3′ end of CTG array, when gaps could be observed in the regular and contiguous peak pattern, but the reaction may sometimes fail, leading to false negative results [ 43, 112].
Even though there are known cases of functional genes with untypical start codons, we decided to restrict our attention to the three typical start codons (ATG, GTG, CTG), hoping that it does not influence our results in a substantial way.
Besides the already mentioned NCIC CTG MA.32 trial it is important to report other recent randomized studies recently performed in this field [ 52, 75– 78] and although the data must be taken with chariness, they seem to confirm the metformin's anticancer effect also in clinical setting.
The second inverted repeat sequence constituted the "slip-out" region; it was adjoined to CTG or CAG units to facilitate its forming a distinct junction arm that minimized alternative mispairings with the opposing complementary CAG or CTG region.
In normal individuals, the length of the CTG repeat is 16 34, whereas it is >74 in affected individuals.
Expansion of the undamaged CTG strand was not documented, although it was proposed to occur through a subsequent misrepair event.
