Miyotonik Distrofi Tip 1’de STR ve MLPA yöntemi kullanılarak yapılan gen analizi ve tekrar sayısının sistemik bulgular ile korelasyonu

Koç A. F.

Uluslarası Akademik Araştırmalar Kongresi, Bolu, Türkiye, 20 - 22 Temmuz 2020, ss.512

  • Basıldığı Şehir: Bolu
  • Basıldığı Ülke: Türkiye
  • Sayfa Sayıları: ss.512


Introduction: Myotonic Dystrophy Type 1 (DM1), dystrophia myotonica which is located on chromosome 19, is the most common type of muscular dystrophy seen in adults due to an increase in trinucleotide (CTG) in the protein kinase (DMPK) gene. It is characterized by myotonia with muscle weakness, cardiac disorders, cataracts, endocrine system involvement, sleep disturbances and baldness. Disease severity depends on the number of repetitions; there are 5 to 37 repetitions in normal individuals, 50 to 150 repetitions in mildly affected person, 100 to 1,000 repetitions in DM patients, and more than 2,000 repetitions in congenital onset patients. The increase in the number of repeats causes the DMPK mRNA and protein levels to decrease. The aim of the study was to evaluate gene expression and to investigate its correlation with systemic findings in patients.

Method: In this study, after the approval of the Local Ethics Committee (July 5, 2019-10), the number of CTG increases in the DMPK gene was determined using the STR and MLPA method in patients diagnosed with DM1 in the light of clinical and electrophysiological findings. The relationship between CTG enlargement and age of onset, duration of disease, and systemic findings was examined. In addition, the expression of the relevant gene was examined, and it worked with the SYBR Green based real time PCR protocol. Results were compared with 33 age-matched healthy control groups. Before starting the statistical analysis, it was determined

whether the data showed normal distribution or not with the Kolmogorov – Smirnov normality test. Normally distributed data were compared with One Way Anova and / or t-test and gene expression analysis, and the values ​​of patient and control cases were compared with the Mann-Whitney U test. SPSS statistics program (SPSS 15.0) and Excel programs were used for these operations.

Results: 24 of the patients were male and 9 were female and their mean age was 41.8 ± 13.5 years. The size of the expanded alleles ranged from 75 to 1300 repeats. While there was a positive correlation between CTG recurrence and the age of onset of the disease, 20 (60.6%) of the patients had cataracts, 8 (24.3%) had cardiac  pathologies and silent cerebral lesions, and 7 (21.2%) had cholelithiasis. No statistically significant correlation was found between CTG expansion and these systemic findings, but a positive correlation was found between disease onset age and CTG expansion (p<;=; 0.001). There was a significant difference in DM1 gene expression values between control and patient groups (p<;=. 001).

Conclusion: It has been shown that there is a positive correlation between CTG width and disease onset age and gene expression. It is also remarkable because it is the first study of gene expression in DM1.