PUBLICATION
A novel in-frame deletion in MYOT causes an early adult onset distal myopathy
- Authors
- Guglielmi, V., Pancheri, E., Cannone, E., Nigro, V., Malatesta, M., Vettori, A., Giorgetti, A., Torella, A., Aurino, S., Cisterna, B., Marchetto, G., Tomelleri, G., Tonin, P., Schiavone, M., Vattemi, G.
- ID
- ZDB-PUB-230810-56
- Date
- 2023
- Source
- Clinical genetics 104(6): 705-710 (Journal)
- Registered Authors
- Vettori, Andrea
- Keywords
- I-band, distal myopathy, myofibrillar myopathy, myotilin, zebrafish model
- MeSH Terms
-
- Adult
- Animals
- Connectin/genetics
- Distal Myopathies*
- Humans
- Microfilament Proteins/genetics
- Muscle Proteins*/genetics
- Muscle, Skeletal/metabolism
- Mutation
- Zebrafish
- PubMed
- 37553249 Full text @ Clin. Genet.
Citation
Guglielmi, V., Pancheri, E., Cannone, E., Nigro, V., Malatesta, M., Vettori, A., Giorgetti, A., Torella, A., Aurino, S., Cisterna, B., Marchetto, G., Tomelleri, G., Tonin, P., Schiavone, M., Vattemi, G. (2023) A novel in-frame deletion in MYOT causes an early adult onset distal myopathy. Clinical genetics. 104(6):705-710.
Abstract
Missense mutations in MYOT encoding the sarcomeric Z-disk protein myotilin cause three main myopathic phenotypes including proximal limb-girdle muscular dystrophy, spheroid body myopathy, and late-onset distal myopathy. We describe a family carrying a heterozygous MYOT deletion (Tyr4_His9del) that clinically was characterized by an early-adult onset distal muscle weakness and pathologically by a myofibrillar myopathy (MFM). Molecular modeling of the full-length myotilin protein revealed that the 4-YERPKH-9 amino acids are involved in local interactions within the N-terminal portion of myotilin. Injection of in vitro synthetized mutated human MYOT RNA or of plasmid carrying its cDNA sequence in zebrafish embryos led to muscle defects characterized by sarcomeric disorganization of muscle fibers and widening of the I-band, and severe motor impairments. We identify MYOT novel Tyr4_His9 deletion as the cause of an early-onset MFM with a distal myopathy phenotype and provide data supporting the importance of the amino acid sequence for the structural role of myotilin in the sarcomeric organization of myofibers.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping