التفاصيل البيبلوغرافية
| العنوان: |
Molecular and Clinical Implications of Variant Repeats in Myotonic Dystrophy Type 1 |
| المؤلفون: |
Stojan Peric, Jovan Pesovic, Dusanka Savic-Pavicevic, Vidosava Rakocevic Stojanovic, Giovanni Meola |
| المصدر: |
International Journal of Molecular Sciences; Volume 23; Issue 1; Pages: 354 |
| بيانات النشر: |
Multidisciplinary Digital Publishing Institute |
| سنة النشر: |
2021 |
| المجموعة: |
MDPI Open Access Publishing |
| مصطلحات موضوعية: |
myotonic dystrophy type 1, DMPK gene, repeat expansions, variant repeats, repeat interruptions, genetic modifier, phenotype variability, age at onset, somatic mosaicism |
| جغرافية الموضوع: |
agris |
| الوصف: |
Myotonic dystrophy type 1 (DM1) is one of the most variable monogenic diseases at phenotypic, genetic, and epigenetic level. The disease is multi-systemic with the age at onset ranging from birth to late age. The underlying mutation is an unstable expansion of CTG repeats in the DMPK gene, varying in size from 50 to >1000 repeats. Generally, large expansions are associated with an earlier age at onset. Additionally, the most severe, congenital DM1 form is typically associated with local DNA methylation. Genetic variability of DM1 mutation is further increased by its structural variations due to presence of other repeats (e.g., CCG, CTC, CAG). These variant repeats or repeat interruptions seem to confer an additional level of epigenetic variability since local DNA methylation is frequently associated with variant CCG repeats independently of the expansion size. The effect of repeat interruptions on DM1 molecular pathogenesis is not investigated enough. Studies on patients indicate their stabilizing effect on DMPK expansions because no congenital cases were described in patients with repeat interruptions, and the age at onset is frequently later than expected. Here, we review the clinical relevance of repeat interruptions in DM1 and genetic and epigenetic characteristics of interrupted DMPK expansions based on patient studies. |
| نوع الوثيقة: |
text |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| العلاقة: |
Molecular Pathology, Diagnostics, and Therapeutics; https://dx.doi.org/10.3390/ijms23010354Test |
| DOI: |
10.3390/ijms23010354 |
| الإتاحة: |
https://doi.org/10.3390/ijms23010354Test |
| حقوق: |
https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: |
edsbas.C5096AAD |
| قاعدة البيانات: |
BASE |
