Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022716 (Menkes)
 1,057 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently, mutations in the gene encoding for the bi-functional enzyme UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE/MNK), symbol GNE or GLCNE (MIM: 603824) [EC 5.1.3.14], were associated with IBM2 (MIM: 600737). IBM2 is a recessively inherited vacuolar myopathy with a prevalence rate of 1-2/1000 amongst people of Iranian-Jewish descent. Seven missense mutations were previously described by Eisenberg et al. All families tested from Iranian and Middle Eastern Jewish ancestry have the same homozygous mutation (bp2186t>c). Here we review the mutations in GNE associated with IBM2, and we describe additional four mutations found in individuals suffering from clinically similar disorder who are not of Iranian or Jewish descent. These findings further confirm that homozygous or compound heterozygous mutations of GNE/MNK gene associated with IBM2 are not confined to any single specific region of the enzyme outside its negative feedback regulatory domain located at codons 249-275.
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PMID:Four novel mutations associated with autosomal recessive inclusion body myopathy (MIM: 600737). 1240 74

Recently, bi-allelic mutations in the gene coding for the bi-functional enzyme UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE/MNK), symbol GNE or GLCNE (MIM: 603824), were associated with the recessively inherited phenotype of IBM2 (MIM: 600737). All patients tested so far have bi-allelic missense mutation(s) of epimerase and/or kinase domains of GNE gene, which clearly explains the recessive inheritance pattern of this phenotype. Single allelic mutations of codons 263-266 of GNE have been implicated as the cause of French type sialuria (MIM: 269921). The dominantly inherited French type sialuria seems to result from defective allosteric feedback inhibitory regulation of GNE/MNK by cytidine monophosphate-N-acetylneuraminic acid (CMP-NANA), resulting in overproduction of cytosolic N-acetylneuraminic acid, and massive urinary excretion of free sialic acid. Because GNE is relatively weakly expressed in skeletal muscle cells, and involvement of other organs are not clinically evident in patients affected with IBM2, it is likely that the missense mutation(s) found in these patients cause a partial reduction of the efficiency of either the epimerase or the kinase activity of this enzyme. Therapeutic dietary modifications are recommended including reduction of ethanol consumption, avoidance of excess selenium, copper, and zinc, and dietary promotion of magnesium (Mg(2+)), which is an essential co-factor for this enzyme.
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PMID:Magnesium may help patients with recessive hereditary inclusion body myopathy, a pathological review. 1245 Jul 72

Hereditary Inclusion Body Myopathy (HIBM, IBM2, MIM:600737) is an autosomal recessive adult onset progressive muscle wasting disorder. It is associated with the degeneration of distal and proximal muscles, while often sparing the quadriceps. The bifunctional enzyme UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE/MNK), encoded by the GNE gene, catalyzes the first two committed, rate-limiting steps in the biosynthesis of N-acetylneunaminic acid (sialic acid). Affected individuals have been identified with mutations in the GNE gene. In the present study, the GNE coding region of 136 symptomatic patients were sequenced. A total of 41 patients were found to have GNE mutations. Eight novel mutations were discovered among seven patients. Of the eight novel mutations, seven were missense (p.I150V, p.Y186C, p.M265T, p.V315T, p.N317D, p.G669R, and p.S699L) and one was nonsense (p.W495X), all of which span the epimerase, kinase, and allosteric domains of GNE. In one patient, one novel mutation was found in the allosteric region and kinase domain of the GNE gene. Mutations in the allosteric region lead to a different disease, sialuria; however, this particular mutation has not been described in patients with sialuria. The pathological significance of this variation with GNE function remains unknown and further studies are needed to identify its connection with HIBM. These findings further expand the clinical and genetic spectrum of HIBM.
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PMID:Novel GNE mutations in autosomal recessive hereditary inclusion body myopathy patients. 2343 77