Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We reported a male patient with X-linked myotubular myopathy in whom MTM 1 gene mutation was first identified in Japan. The patient had 9-nucleotide insertion between exons 11 and 12 due to aberrant splicing. The patient showed severe hypotonia and generalized muscle weakness at birth. Mechanical ventilation and tube feeding were necessary because of poor spontaneous respiration and sucking. On muscle biopsy, most of the muscle fibers were small and round, and had peripheral halos, showing immaturity. He had a moderate ventricular dilatation and mild brain atrophy on brain CT and MRI. However, whether these findings are causally related to the splice-site mutation remained obscure.
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PMID:[X-linked recessive myotubular myopathy with a splice-site mutation in the myotubularin gene]. 984 18

Myotubular myopathy (MTM1) is an X-linked disease, characterized by severe neonatal hypotonia and generalized muscle weakness, with pathological features suggesting an impairment in maturation of muscle fibres. The MTM1 gene encodes a protein (myotubularin) with a phosphotyrosine phosphatase consensus. It defines a family of at least nine genes in man, including the antiphosphatase hMTMR5/Sbf1 and hMTMR2, recently found mutated in a recessive form of Charcot-Marie-Tooth disease. Myotubularin shows a dual specificity protein phosphatase activity in vitro. We have performed an in vivo test of tyrosine phosphatase activity in Schizosaccharomyces pombe, indicating that myotubularin does not have a broad specificity tyrosine phosphatase activity. Expression of active human myotubularin inhibited growth of S.pombe and induced a vacuolar phenotype similar to that of mutants of the vacuolar protein sorting (VPS) pathway and notably of mutants of VPS34, a phosphatidylinositol 3-kinase (PI3K). In S.pombe cells deleted for the endogenous MTM homologous gene, expression of human myotubularin decreased the level of phosphatidylinositol 3-phosphate (PI3P). We have created a substrate trap mutant which shows relocalization to plasma membrane projections (spikes) in HeLa cells and was inactive in the S.pombe assay. This mutant, but not the wild-type or a phosphatase site mutant, was able to immunoprecipitate a VPS34 kinase activity. Wild-type myotubularin was also able to directly dephosphorylate PI3P and PI4P in vitro. Myotubularin may thus decrease PI3P levels by down-regulating PI3K activity and by directly degrading PI3P.
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PMID:Myotubularin, a phosphatase deficient in myotubular myopathy, acts on phosphatidylinositol 3-kinase and phosphatidylinositol 3-phosphate pathway. 1100 25

The myotubular myopathy is an X-linked centronuclear myopathy characterized by severe neonatal hypotonia and generalized muscle weakness which most frequently results in the premature death of the newborn infants by respiratory failure. The characteristic muscle histopathology consists in centrally positioned nuclei in most muscle fibers. In 1996, the gene responsible for the disease, MTM1, was identificated in Xq28 region. Since then, more than hundred mutations have been isolated. Genotype - phenotype correlation is complex because mutations are found along the entire coding sequence of the MTM1 gene. Most mutations are associated with very severe phenotype with death before the first year of life, however a milder phenotype has been individualized. It is important to be aware of the existence of such milder MTM phenotype because in those patients a very mild expression permit normal life into adulthood.
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PMID:[Myotubular myopathy]. 1111 47

MTM1, MTMR2, and SBF2 belong to a family of proteins called the myotubularins. X-linked myotubular myopathy, a severe congenital disorder characterized by hypotonia and generalized muscle weakness in newborn males, is caused by mutations in MTM1 (Laporte et al., 1996). Charcot-Marie-Tooth types 4B1 and 4B2 are severe demyelinating neuropathies caused by mutations in MTMR2 (Bolino et al., 2000) and SBF2/MTMR13 (Senderek et al., 2003), respectively. Although several myotubularins are known to regulate phosphoinositide-phosphate levels in cells, little is known about the actual cellular process that is defective in patients with these diseases. Mutations in worm MTM-6 and MTM-9, myotubularins belonging to two subgroups, disorganize phosphoinositide 3-phosphate localization and block endocytosis in the coelomocytes of Caenorhabditis elegans. We demonstrate that MTM-6 and MTM-9 function as part of a complex to regulate an endocytic pathway that involves the Arf6 GTPase, and we define protein domains required for MTM-6 activity.
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PMID:Disease-related myotubularins function in endocytic traffic in Caenorhabditis elegans. 1456 69