Preliminary Findings on CTG Expansion Determination in Different Tissues from Patients with Myotonic Dystrophy Type 1

Abstract

Myotonic Dystrophy type 1 (DM1) is characterized by a high genetic and clinical variability. Determination of the genetic variability in DM1 might help to determine whether there is an association between CTG (Cytosine-Thymine-Guanine) expansion and the clinical manifestations of this condition. We studied the variability of the CTG expansion (progenitor, mode, and longest allele, respectively, and genetic instability) in three tissues (blood, muscle, and tissue) from eight patients with DM1. We also studied the association of genetic data with the patients’ clinical characteristics. Although genetic instability was confirmed in all the tissues that we studied, our results suggest that CTG expansion is larger in muscle and skin cells compared with peripheral blood leukocytes. While keeping in mind that more research is needed in larger cohorts, we have provided preliminary evidence suggesting that the estimated progenitor CTG size in muscle could be potentially used as an indicator of age of disease onset and muscle function impairment.

Both cis and trans-acting genetic factors drive somatic instability in female carriers of the FMR1 premutation

“…In an FXD mouse model, blood shows much less expansion than the brain 48 . A similar difference between the extent of expansion in blood and brain has been reported in other Repeat Expansion Diseases 55 – 58 . Thus, in PM carriers where expansion can be detected in blood, the extent of expansion in the brain maybe even larger.…”

Characterization of RAN Translation and Antisense Transcription in Primary Cell Cultures of Patients with Myotonic Dystrophy Type 1

“…Our study population consisted of ten DM1 patients, of which the clinical characteristics have been, in part, described previously ( Table 1 , [ 12 , 13 ]). Eight out of ten DM1 patients provided skin and muscle biopsies, whereas from the other two only lymphoblastoid cell lines were available.…”

Clinical characteristics of different forms of myotonic dystrophy type 1

“…Однако корреляция генотип-фенотип имеет место не во всех случаях из-за соматической нестабильности мутантных аллелей. Наибольшей стабильностью CTGповторов обладают лейкоциты по сравнению с миоцитами и фибробластами [8]. Таким образом, соматический мозаицизм наблюдается как в различных тканях, так и в пределах одной ткани.…”

“…Сердечно-сосудистые нарушения. Нарушения со стороны сердечно-сосудистой системы наряду с дыхательной недостаточностью являются ведущими причинами смерти у пациентов при классической форме МД1 [8]. Кардиологические симптомы обычно проявляются в виде прогрессирующей атриовентрикулярной блокады, несколько реже -дисфункции синусового узла, желудочковой и предсердной фибрилляции и трепетания предсердий [28,50].…”