Large TRAPPC11 gene deletions as a cause of muscular dystrophy and their estimated genesis
Language English Country Great Britain, England Media electronic
Document type Journal Article, Case Reports
PubMed
38955476
DOI
10.1136/jmg-2024-110016
PII: jmg-2024-110016
Knihovny.cz E-resources
- Keywords
- Neuromuscular Diseases,
- MeSH
- Gene Deletion MeSH
- Child MeSH
- Adult MeSH
- Muscle, Skeletal pathology metabolism MeSH
- Humans MeSH
- Mutation, Missense genetics MeSH
- Muscular Dystrophies * genetics pathology MeSH
- High-Throughput Nucleotide Sequencing MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Case Reports MeSH
- Names of Substances
- TRAPPC11 protein, human MeSH Browser
BACKGROUND: Transport protein particle (TRAPP) is a multiprotein complex that functions in localising proteins to the Golgi compartment. The TRAPPC11 subunit has been implicated in diseases affecting muscle, brain, eye and to some extent liver. We present three patients who are compound heterozygotes for a missense variant and a structural variant in the TRAPPC11 gene. TRAPPC11 structural variants have not yet been described in association with a disease. In order to reveal the estimated genesis of identified structural variants, we performed sequencing of individual breakpoint junctions and analysed the extent of homology and the presence of repetitive elements in and around the breakpoints. METHODS: Biochemical methods including isoelectric focusing on serum transferrin and apolipoprotein C-III, as well as mitochondrial respiratory chain complex activity measurements, were used. Muscle biopsy samples underwent histochemical analysis. Next-generation sequencing was employed for identifying sequence variants associated with neuromuscular disorders, and Sanger sequencing was used to confirm findings. RESULTS: We suppose that non-homologous end joining is a possible mechanism of deletion origin in two patients and non-allelic homologous recombination in one patient. Analyses of mitochondrial function performed in patients' skeletal muscles revealed an imbalance of mitochondrial metabolism, which worsens with age and disease progression. CONCLUSION: Our results contribute to further knowledge in the field of neuromuscular diseases and mutational mechanisms. This knowledge is important for understanding the molecular nature of human diseases and allows us to improve strategies for identifying disease-causing mutations.
Central European Institute of Technology Masaryk University Brno Czech Republic
Centre of Molecular Biology and Genetics Brno University Hospital Brno Czech Republic
National Centre for Biomolecular Research Faculty of Science Masaryk University Brno Czech Republic
References provided by Crossref.org
