Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mammalian O-mannosylation, although an uncommon type of protein modification, is essential for normal brain and muscle development. Defective O-mannosylation causes congenital muscular dystrophy with abnormal neuronal migration [Walker-Warburg syndrome (WWS)]. Here, we have identified and cloned rat Pomt1 and Pomt2, which are homologues of human POMT1 and POMT2, with identities of 86 and 90%, respectively, at the amino acid level. Coexpression of both genes was found to be necessary for enzymatic activity, as is the case with human POMT1 and POMT2. Northern blot and reverse transcriptase polymerase chain reaction (RT-PCR) analyses revealed that rat Pomt1 and Pomt2 are expressed in all tissues but most strongly in testis. In situ hybridization histochemistry of rat brain revealed that Pomt1 and Pomt2 mRNA are coexpressed in neurons (dentate gyrus and CA1-CA3 region of the hippocampus and cerebellar Purkinje cells). Two transcription-initiation sites were observed in rat Pomt2, resulting in two forms: a testis form and a somatic form. The two forms had equal protein O-mannosyltransferase activity when coexpressed with rat Pomt1. Coexpression studies also showed that the human and rat protein O-mannosyltransferases are interchangeable, providing further evidence for the closeness of their structures.
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PMID:Molecular cloning and characterization of rat Pomt1 and Pomt2. 1670 66

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.
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PMID:Affinity proteomics within rare diseases: a BIO-NMD study for blood biomarkers of muscular dystrophies. 2492 Jun 7