| Title: |
Comprehensive analysis across SMN2 excludes DNA methylation as an epigenetic biomarker for spinal muscular atrophy |
| Authors: |
Zwartkruis, Maria M.; Kortooms,Joris V.; Gommers, Demi; Elferink, Martin G.; Signoria, Ilaria; van der Sel,Joyce; Hop, Paul J.; Zwamborn, Ramona A.J.; Geene, Robin; Green,Jared W.; van Deutekom, Hanneke W.M.; van Rheenen, Wouter; Veldink, Jan H.; Asselman, Fay Lynn; Wadman, Renske I.; van der Pol, W. Ludo; van Haaften, Gijs W.; Groen, Ewout J.N.; Genetica; Projectafdeling SvS; Genetica Medische Informatica; Neurogenetica; CMM USEQ Facility; Cancer; Neurologen; Brain; Neuromuscular Disorders; Genetic Risks; Verpleegkundig Specialisten; Genetica Sectie Research; Child Health |
| Publication Year: |
2025 |
| Subject Terms: |
Health sciences; Internal medicine; Medical specialty; Medicine; Neurology; General |
| Description: |
Spinal muscular atrophy (SMA) is a severe neurodegenerative disease caused by defects in the survival motor neuron 1 (SMN1) gene. Although disease severity partially correlates with SMN2 copy number, significant variability in disease severity and treatment response remains unexplained, prompting a search for additional biomarkers. Using native, long-read nanopore and targeted short-read bisulfite sequencing, we analyzed methylation patterns across the 30 kb SMN2 gene. Our long-read analysis of 29 SMA patients identified tissue-specific variation in SMN2 intronic regions and the 3′UTR. Further analysis of blood-derived DNA of 365 SMA patients identified no association between SMN2 methylation and disease severity or treatment response, excluding blood-derived DNA methylation as a predictive biomarker. However, we discovered significant age-associated variation in SMN2 methylation in intron 1 and the 3′UTR, suggesting a possible role in modifying SMN expression during development and aging. This study provides a framework for detailed methylation analysis in complex genetic regions. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
https://dspace.library.uu.nl/handle/1874/466117 |
| Availability: |
https://dspace.library.uu.nl/handle/1874/466117 |
| Rights: |
info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.15DF08CB |
| Database: |
BASE |