title: A cross sectional study of two independent cohorts identifies serum biomarkers for facioscapulohumeral muscular dystrophy (FSHD).
abstract: Measuring the severity and progression of facioscapulohumeral muscular dystrophy (FSHD) is particularly challenging because muscle weakness progresses over long periods of time and can be sporadic. Biomarkers are essential for measuring disease burden and testing treatment strategies. We utilized the sensitive, specific, high-throughput SomaLogic proteomics platform of 1129 proteins to identify proteins with levels that correlate with FSHD severity in a cross-sectional study of two independent cohorts. We discovered biomarkers that correlate with clinical severity and disease burden measured by magnetic resonance imaging. Sixty-eight proteins in the Rochester cohort (n = 48) and 51 proteins in the Seattle cohort (n = 30) had significantly different levels in FSHD-affected individuals when compared with controls (p-value ≤ .005). A subset of these varied by at least 1.5 fold and four biomarkers were significantly elevated in both cohorts. Levels of creatine kinase MM and MB isoforms, carbonic anhydrase III, and troponin I type 2 reliably predicted the disease state and correlated with disease severity. Other novel biomarkers were also discovered that may reveal mechanisms of disease pathology. Assessing the levels of these biomarkers during clinical trials may add significance to other measures of quantifying disease progression or regression.
authors.affiliation: Department of Pediatrics, Div. of Genetic Med., University of Washington, Seattle, WA, USA.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Petek
authors.affiliation: Department of Pediatrics, Div. of Genetic Med., University of Washington, Seattle, WA, USA.
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Rickard
authors.affiliation: Department of Radiology, Seattle Children's Hospital, Seattle, WA, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Budech
authors.affiliation: Department of Radiology, Seattle Children's Hospital, Seattle, WA, USA.
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Poliachik
authors.affiliation: Department of Radiology, Seattle Children's Hospital, Seattle, WA, USA.
authors.forename: Dennis
authors.initials: D
authors.lastname: Shaw
authors.affiliation: Department of Radiology, Seattle Children's Hospital, Seattle, WA, USA.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Ferguson
authors.affiliation: Department of Neurology, University of Rochester, Rochester, NY, USA.
authors.forename: Rabi
authors.initials: R
authors.lastname: Tawil
authors.affiliation: Department of Radiology, Seattle Children's Hospital, Seattle, WA, USA.
authors.forename: Seth D
authors.initials: SD
authors.lastname: Friedman
authors.affiliation: Department of Pediatrics, Div. of Genetic Med., University of Washington, Seattle, WA, USA. Electronic address: dgmiller@uw.edu.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Miller
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D017281:Cost of Illness; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020391:Muscular Dystrophy, Facioscapulohumeral / Q000097:blood* / Q000000981:diagnostic imaging; D020543:Proteome; D040901:Proteomics; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D015415:Biomarkers; D020543:Proteome
keywords: Biomarker; Carbonic anhydrase; Creatine kinase; D4Z4; DUX4; FSHD; Facioscapulohumeral; Muscular dystrophy; Proteomics; Troponin