Abstract-Text (inkl. Referenzen)
X-linked dystrophinopathies are caused by different types of mutations in the Duchenne muscular dystrophy (DMD) gene. The reading-frame rule predicts the disease course in 90% of DMD cases. The encoded protein dystrophin stabilises the plasma membrane of the muscle cell as part of the dystrophin-glycoprotein-complex. Microtubule associated serine threonine protein kinase 1 (MAST1) phosphorylates dystrophin and links dystrophin via syntrophin to microtubules.
We screened our cohort of X-linked dystrophinopathy patients treated at the Department of Pediatric Neurology of the University Hospital Essen for causative DMD
variants and their corresponding phenotype. Microscopic studies on muscle biopsies were performed and dystrophin and MAST1 abundances were measured by ELISA.
Here, we report on 16 novel pathogenic variants, which have not yet been described in literature. Clinical and genetic findings were correlated with abundances of dystrophin and MAST1 showing first indications for an interdependency. Lower dystrophin levels seem to cause an upregulation of MAST1, possibly to improve dystrophin linkage in order to increase the stability of the cytoskeleton.
Knowing about novel genotypes and evolving phenotypes is very important in terms of counselling of affected families. Analysing dystrophin levels as well as interaction partners like MAST1 is crucial to better understand the pathophysiology of dystrophin expression.