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)

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

GNE myopathy is an autosomal recessive muscular disorder caused by mutations in the gene encoding the key enzyme in sialic acid biosynthesis, UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE/MNK). Here, we report two siblings with myopathy with rimmed vacuoles and congenital thrombocytopenia who harbored two compound heterozygous GNE mutations, p.V603L and p.G739S. Thrombocytopenia, which is characterized by shortened platelet lifetime rather than ineffective thrombopoiesis, has been observed since infancy. We performed exome sequencing and array CGH to identify the underlying genetic etiology of thrombocytopenia. No pathogenic variants were detected among the known causative genes of recessively inherited thrombocytopenia; yet, candidate variants in two genes that followed an autosomal recessive mode of inheritance, including previously identified GNE mutations, were detected. Alternatively, it is possible that the decreased activity of GNE/MNK itself, which would lead to decreased sialic content in platelets, is associated with thrombocytopenia in these patients. Further investigations are required to clarify the association between GNE myopathy and the pathogenesis of thrombocytopenia.
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PMID:GNE myopathy associated with congenital thrombocytopenia: a report of two siblings. 2525 49


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