Abstract
Limb-girdle muscular dystrophies (LGMD) are clinically and genetically heterogeneous conditions, presenting with a wide clinical spectrum, leading to progressive proximal weakness caused by loss of muscle fibers. MiR-206 is a member of myomiRNAs, a group of miRNAs with important function in skeletal muscle. Our aim is to determine the value of miR-206 in detecting muscle disease evolution in patients affected by LGMD. We describe clinical features, disease history and progression of eleven patients affected by various types of LGMD: transportinopathy, sarcoglycanopathy and calpainopathy. We analyzed the patients’ mutations and we studied the circulating miR-206 in serum by qRT-PCR; muscle MRI was done with a 1.5 Tesla apparatus. The severe evolution of disease type is associated with the expression levels of miR-206, which was significantly elevated in our LGMD patient cohort in comparison with a control group. In particular, we observed an over-expression of miR-206 that was 50–80 folds elevated in two patients with a severe and early disease course in the transportinopathy and calpainopathy sub-types. The functional impairment was observed clinically and muscle loss and atrophy documented by muscle MRI. This study provides the first evidence that miR-206 is associated with phenotypic expression and it could be used as a prognostic indicator of LGMD disease progression.
Highlights
The limb-girdle muscular dystrophies (LGMD) include a group of clinically and genetically heterogeneous diseases that lead to progressive weakness, predominantly proximal to the presentation, caused by loss of muscle fibers
Disease history and progression of eleven patients affected by various types of Limb-girdle muscular dystrophies (LGMD): transportinopathy, sarcoglycanopathy and calpainopathy
No efficacy therapies are available for LGMD, but, only in few α-sarcoglycanopathy cases, steroids influenced the patient’s clinical status with drug therapy, while in the βsarcoglycanopathy patient we report a subsequent heart transplant was done with success, since his skeletal muscle weakness was not deteriorating
Summary
The limb-girdle muscular dystrophies (LGMD) include a group of clinically and genetically heterogeneous diseases that lead to progressive weakness, predominantly proximal to the presentation, caused by loss of muscle fibers. Common clinical signs useful for classification include that affected individuals must achieve independent walking ability and laboratory-based data, such as elevated (CK)and muscle biopsy histopathology showing dystrophic features, eventually leading to end-stage disease and observation of degenerative changes in MRI [1,2,3]. The progression of muscle weakness is usually symmetrical and variable between individuals and the genetic type These disorders present a broad spectrum of muscle involvement and atrophy, ranging from severe with early-onset and rapid progression, such as those with childhood-onset, to a milder form with late-onset
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
