Fibronectin is a serum biomarker for Duchenne muscular dystrophy.
PURPOSE
To identify and validate serum biomarkers for the progression of Duchenne muscular dystrophy (DMD) using a MS-based bottom-up pipeline.


EXPERIMENTAL DESIGN
We used a bottom-up proteomics approach, including a protein concentration equalization step, different proteolytic digestions, and MS detection schemes, to identify candidate biomarkers in serum samples from control subjects and DMD patients. Fibronectin was chosen for follow-up based on the differences in peptide spectral counts and sequence coverage observed between the DMD and control groups. Subsequently, fibronectin levels were determined with ELISA in 68 DMD patients, 38 milder Becker muscular dystrophy patients, 33 patients with other neuromuscular disorders, and 15 age-matched adult and child controls.


RESULTS
There was a significant increase in fibronectin levels in DMD patients compared to age-matched controls. Fibronectin levels in patients with Becker muscular dystrophy, Bethlem myopathy, or myasthenia gravis were comparable to control levels. Progressive elevation in fibronectin levels was observed in longitudinal samples from 22 DMD patients followed up for a period of 6 months up to 4 years.


CONCLUSION AND CLINICAL RELEVANCE
This study suggests that serum fibronectin levels may constitute a promising biomarker to monitor disease progression in DMD patients.
['Cynthia Martin|F|F|', 'Hiller|Monika|M|', 'Spitali|Pietro|P|', 'Oonk|Stijn|S|', 'Dalebout|Hans|H|', 'Palmblad|Magnus|M|', 'Chaouch|Amina|A|', 'Guglieri|Michela|M|', 'Straub|Volker|V|', 'Lochmüller|Hanns|H|', 'Niks|Erik H|EH|', 'Verschuuren|Jan J G M|JJ|', 'Aartsma-Rus|Annemieke|A|', 'Deelder|André M|AM|', 'van der Burgt|Yuri E M|YE|', "'t Hoen|Peter A C|PA|"]
D000293:Adolescent D000328:Adult D015415:Biomarkers D002648:Child D002675:Child, Preschool D003286:Contracture D005260:Female D005353:Fibronectins D006801:Humans D008297:Male D013058:Mass Spectrometry D008875:Middle Aged D018482:Muscle, Skeletal D009136:Muscular Dystrophies D020388:Muscular Dystrophy, Duchenne D009157:Myasthenia Gravis
Fibronectin Biomarker Duchenne muscular dystrophy Spectral counting