Defective GFPT1 causes CMSTA1

Stable Identifier
Homo sapiens
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Glucosamine-fructose 6-phosphate aminotransferases 1 and 2 (GFPT1,2) are the first and rate-limiting enzymes in the hexosamine synthesis pathway, and thus formation of hexosamines like N-acetylglucosamine (GlcNAc). These enzymes probably play a role in limiting the availability of substrates for the N- and O-linked glycosylation of proteins. GFPT1 and 2 are required for normal functioning of neuromuscular synaptic transmission. Defects in GFPT1 lead to myasthenia, congenital, with tubular aggregates 1 (CMSTA1; MIM:610542), characterised by altered muscle fibre morphology and impaired neuromuscular junction development. Sufferers of CMSTA1 show a good response to acetylcholinesterase inhibitors (Senderek et al. 2011). The missense mutations observed do not always result in significant reduction in enzyme activity, but biopsies show reduced amounts of GFPT1 protein suggesting increased turnover or defective translation (Senderek et al. 2011).

Literature References
PubMed ID Title Journal Year
21310273 Hexosamine biosynthetic pathway mutations cause neuromuscular transmission defect

Senderek, J, Müller, JS, Dusl, M, Strom, TM, Guergueltcheva, V, Diepolder, I, Laval, SH, Maxwell, S, Cossins, J, Krause, S, Muelas, N, Vilchez, JJ, Colomer, J, Mallebrera, CJ, Nascimento, A, Nafissi, S, Kariminejad, A, Nilipour, Y, Bozorgmehr, B, Najmabadi, H, Rodolico, C, Sieb, JP, Steinlein, OK, Schlotter, B, Schoser, B, Kirschner, J, Herrmann, R, Voit, T, Oldfors, A, Lindbergh, C, Urtizberea, A, von der Hagen, M, Hübner, A, Palace, J, Bushby, K, Straub, V, Beeson, D, Abicht, A, Lochmüller, H

Am J Hum Genet 2011
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