Dataset Information

Affinity proteomics within rare diseases: a BIO-NMD study for blood biomarkers of muscular dystrophies.

ABSTRACT: Despite the recent progress in the broad-scaled analysis of proteins in body fluids, there is still a lack in protein profiling approaches for biomarkers of rare diseases. Scarcity of samples is the main obstacle hindering attempts to apply discovery driven protein profiling in rare diseases. We addressed this challenge by combining samples collected within the BIO-NMD consortium from four geographically dispersed clinical sites to identify protein markers associated with muscular dystrophy using an antibody bead array platform with 384 antibodies. Based on concordance in statistical significance and confirmatory results obtained from analysis of both serum and plasma, we identified eleven proteins associated with muscular dystrophy, among which four proteins were elevated in blood from muscular dystrophy patients: carbonic anhydrase III (CA3) and myosin light chain 3 (MYL3), both specifically expressed in slow-twitch muscle fibers and mitochondrial malate dehydrogenase 2 (MDH2) and electron transfer flavoprotein A (ETFA). Using age-matched sub-cohorts, 9 protein profiles correlating with disease progression and severity were identified, which hold promise for the development of new clinical tools for management of dystrophinopathies.

SUBMITTER: Ayoglu B

PROVIDER: S-EPMC4119355 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Affinity proteomics within rare diseases: a BIO-NMD study for blood biomarkers of muscular dystrophies.

Ayoglu Burcu B Chaouch Amina A Lochmüller Hanns H Politano Luisa L Bertini Enrico E Spitali Pietro P Hiller Monika M Niks Eric H EH Gualandi Francesca F Gualandi Francesca F Pontén Fredrik F Bushby Kate K Aartsma-Rus Annemieke A Schwartz Elena E Le Priol Yannick Y Straub Volker V Uhlén Mathias M Cirak Sebahattin S 't Hoen Peter A C PA Muntoni Francesco F Ferlini Alessandra A Schwenk Jochen M JM Nilsson Peter P Al-Khalili Szigyarto Cristina C

EMBO molecular medicine 20140701 7

Despite the recent progress in the broad-scaled analysis of proteins in body fluids, there is still a lack in protein profiling approaches for biomarkers of rare diseases. Scarcity of samples is the main obstacle hindering attempts to apply discovery driven protein profiling in rare diseases. We addressed this challenge by combining samples collected within the BIO-NMD consortium from four geographically dispersed clinical sites to identify protein markers associated with muscular dystrophy usin ...[more]

PMID: 24920607

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Project description:Muscular dystrophies and congenital myopathies arise from specific genetic mutations causing skeletal muscle weakness that reduces quality of life. Muscle health relies on resident muscle stem cells called satellite cells, which enable life-course muscle growth, maintenance, repair and regeneration. Such tuned plasticity gradually diminishes in muscle diseases, suggesting compromised satellite cell function. A central issue however, is whether the pathogenic mutation perturbs satellite cell function directly and/or indirectly via an increasingly hostile microenvironment as disease progresses. Here, we explore the effects on satellite cell function of pathogenic mutations in genes (myopathogenes) that associate with muscle disorders, to evaluate clinical and muscle pathological hallmarks that define dysfunctional satellite cells. We deploy transcriptomic analysis and comparison between muscular dystrophies and myopathies to determine the contribution of satellite cell dysfunction using literature, expression dynamics of myopathogenes and their response to the satellite cell regulator PAX7. Our multimodal approach extends current pathological classifications to define Satellite Cell-opathies: muscle disorders in which satellite cell dysfunction contributes to pathology. Primary Satellite Cell-opathies are conditions where mutations in a myopathogene directly affect satellite cell function, such as in Progressive Congenital Myopathy with Scoliosis (MYOSCO) and Carey-Fineman-Ziter Syndrome (CFZS). Primary satellite cell-opathies are generally characterised as being congenital with general hypotonia, and specific involvement of respiratory, trunk and facial muscles, although serum CK levels are usually within the normal range. Secondary Satellite Cell-opathies have mutations in myopathogenes that affect both satellite cells and muscle fibres. Such classification aids diagnosis and predicting probable disease course, as well as informing on treatment and therapeutic development.

Dataset Information

Affinity proteomics within rare diseases: a BIO-NMD study for blood biomarkers of muscular dystrophies.

Publications

Affinity proteomics within rare diseases: a BIO-NMD study for blood biomarkers of muscular dystrophies.

Similar Datasets

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