• Home
  • Search Results
  • Proteomics profiling of urine reveals specific titin fragments as biomarkers of Duchenne muscular dystrophy.

Proteomics profiling of urine reveals specific titin fragments as biomarkers of Duchenne muscular dystrophy.

Neuromuscular disorders : NMD (2014-05-13)
Jeremy Rouillon, Aleksandar Zocevic, Thibaut Leger, Camille Garcia, Jean-Michel Camadro, Bjarne Udd, Brenda Wong, Laurent Servais, Thomas Voit, Fedor Svinartchouk
ABSTRACT

Diagnosis of muscular dystrophies is currently based on invasive methods requiring muscle biopsies or blood tests. The aim of the present study was to identify urinary biomarkers as a diagnostic tool for muscular dystrophies. Here, the urinary proteomes of Duchenne muscular dystrophy (DMD) patients and healthy donors were compared with a bottom-up proteomic approach. Label-free analysis of more than 1100 identified proteins revealed that 32 of them were differentially expressed between healthy controls and DMD patients. Among these 32 proteins, titin showed the highest fold change between healthy subjects and DMD patients. Interestingly, most of the sequenced peptides belong to the N-terminal and C-terminal parts of titin, and the presence of the corresponding fragments in the urine of DMD patients was confirmed by Western blot analysis. Analysis of a large cohort of DMD patients and age-matched controls (a total of 104 individuals aged from 3 to 20 years) confirmed presence of the N-ter fragment in all but two patients. In two DMD patients aged 16 and 20 years this fragment was undetectable and two healthy controls of 16 and 19 years with serum CK >800 IU/L demonstrated a low level of the fragment. N- and C-terminal titin fragments were also detected in urine from patients with other muscular dystrophies such as Becker muscular dystrophy and Limb-girdle muscular dystrophy (type 1D, 2D and 2J) but not in neurogenic spinal muscular atrophy. They were also present in urine of dystrophin-deficient animal models (GRMD dogs and mdx mice). Titin is the first urinary biomarker that offers the possibility to develop a simple, non-invasive and easy-to-use test for pre-screening of muscular dystrophies, and may also prove to be useful for the non-invasive follow up of DMD patients under treatment.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Iodoacetamide, BioUltra
Sigma-Aldrich
BIS-TRIS, ≥98.0% (titration)
Sigma-Aldrich
Iodoacetamide, Single use vial of 56 mg
Sigma-Aldrich
Iodoacetamide, ≥99% (NMR), crystalline
SAFC
BIS-TRIS
Sigma-Aldrich
BIS-TRIS, BioXtra, ≥98.0% (titration)
Sigma-Aldrich
BIS-TRIS, BioUltra, ≥99.0% (NT)
Sigma-Aldrich
BIS-TRIS, BioPerformance Certified, suitable for cell culture, suitable for insect cell culture, ≥98.0%
SAFC
BIS-TRIS
SAFC
Iodoacetamide
Sigma-Aldrich
Anti-Human (κ-chain specific), F(ab′)2 fragment antibody produced in goat, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Anti-Human (λ-chain specific), F(ab′)2 fragment antibody produced in goat, affinity isolated antibody, buffered aqueous solution