An international collaboration describes a cohort of 33 patients with slowly progressive myopathy, beginning in childhood and associated with co-segregation of SRPK3 and TTN variants.
- Axial and proximal muscle involvement affected the lower limbs more than the upper limbs.
- Respiratory muscle involvement was present in 14 of the patients; three had dilated cardiomyopathy probably due to the TTN gene mutation.
- Muscle biopsies showed internalisation of nuclei and structures similar to cores.
- The study of the zebrafish double mutant for SRPK3 and TTN, a model which reproduces the characteristics of the human disease, suggests that the interactions between the muscle kinase SRPK3 and titin are post-transcriptional.
The authors conclude that this digenic inheritance associating genes involved in post-translational processes and genes constituting their direct or indirect target could represent a new model for diseases that were previously thought to be monogenic.
