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)

Plasma membrane repair is an essential process for maintenance of homeostasis at the cellular and tissue levels, whereas compromised repair capacity contributes to degenerative human diseases. Our recent studies show that MG53 is essential for muscle membrane repair, and defects in MG53 function are linked to muscular dystrophy and cardiac dysfunction. Here we report that polymerase I and transcript release factor (PTRF), a gene known to regulate caveolae membrane structure, is an indispensable component of the membrane repair machinery. PTRF acts as a docking protein for MG53 during membrane repair potentially by binding exposed membrane cholesterol at the injury site. Cells lacking expression of endogenous PTRF show defective trafficking of MG53 to membrane injury sites. A mutation in PTRF associated with human disease results in aberrant nuclear localization of PTRF and disrupts MG53 function in membrane resealing. Although RNAi silencing of PTRF leads to defective muscle membrane repair, overexpression of PTRF can rescue membrane repair defects in dystrophic muscle. Our data suggest that membrane-delimited interaction between MG53 and PTRF contributes to initiation of cell membrane repair, which can be an attractive target for treatment or prevention of tissue injury in human diseases.
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PMID:Polymerase transcriptase release factor (PTRF) anchors MG53 protein to cell injury site for initiation of membrane repair. 2134 2

A boy with congenital generalized lipodystrophy type 4 with muscular dystrophy presented in infancy with delay in motor milestones and a persistent elevation of CK. There was no associated mental retardation. He was followed up to 3 years and 11 months; he had a homozygous c.696_697insC mutation in polymerase I and transcript release factor (PTRF). He started to walk at 2 years and 6 months although he did not have mental retardation. Insulin resistance appeared at 3 years and 11 months of age. PTRF immunostaining positivity was absent in the muscle but caveolin-3 was preserved in the sarcolemma at 16 months of age. Secondary deficiency of caveolins may be closely associated with disease progression.
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PMID:Congenital generalized lipodystrophy type 4 with muscular dystrophy: clinical and pathological manifestations in early childhood. 2348 63

Caveolinopathies, caused by CAV3 mutations, can include several phenotypes such as rippling muscle disease, limb-girdle muscular dystrophy type 1C, distal myopathy, familial hypertrophic cardiomyopathy, and idiopathic hyperCKemia. Here we present characteristic skeletal muscle imaging findings in four patients with genetically defined childhood-onset RMD caused by CAV3 mutations and in one patient with congenital generalized lipodystrophy type 4 with muscular dystrophy due to polymerase I and transcript release factor (PTRF) mutations, which may have caused secondary deficiency of caveolin-3. Muscle MRI revealed that the rectus femoris and semitendinosus muscles were most commonly affected in the rippling muscle disease patients. Peripheral changes in the rectus femoris were specific and observed even in one of the younger patients in this study. Furthermore, muscle involvement extended to the semitendinosus muscles, biceps femoris, and gracilis with disease progression or increase in its severity. Similar patterns of involvement were observed on reviewing skeletal muscle images of various previously reported phenotypes of caveolinopathy; interestingly, patients with secondary deficiency of caveolin due to PTRF mutations revealed the same pattern. Thus, primary caveolinopathies and secondary deficiency of caveolin demonstrated specific findings on skeletal muscle imaging, regardless of the broad phenotypic spectrum of these two conditions.
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PMID:Characteristic findings of skeletal muscle MRI in caveolinopathies. 3017 72

Congenital generalized lipodystrophy type 4 (CGL4) is a rare disease caused by mutations in the gene polymerase I and transcript release factor (PTRF), the main symptoms of which are systemic reductions in adipose tissue and muscular dystrophy. The strategy of treating CGL4 is to improve the insulin resistance and hypertriglyceridemia that result from systemic reductions in adipose tissue. Metreleptin, a synthetic analog of human leptin, is effective against generalized lipodystrophies; however, there are no reports of the use of metreleptin in the treatment of CGL4. Herein, we discuss the treatment of a six-year-old boy diagnosed with CGL4 due to a homozygous mutation in PTRF with metreleptin. His serum triglyceride level and homeostasis model assessment of insulin resistance (HOMA-IR) value decreased after two months of metreleptin treatment. However, the efficacy of metreleptin gradually decreased, and the treatment was suspended because anaphylaxis occurred after the dosage administered was increased. Subsequently, his serum triglyceride level and HOMA-IR value significantly increased. Anti-metreleptin-neutralizing antibodies were detected in his serum, which suggested that these antibodies reduced the efficacy of metreleptin and caused increased hypersensitivity. Thus, metreleptin appeared to be efficacious in the treatment of CGL4 in the short term, although an adverse immune response resulted in treatment suspension. Further studies are needed to evaluate metreleptin treatments for CGL4.
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PMID:Metreleptin treatment for congenital generalized lipodystrophy type 4 (CGL4): a case report. 3074 27