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Senderek, J.* ; Müller, J.S.* ; Dusl, M. ; Strom, T.M. ; Guergueltcheva, V.* ; Diepolder, I.* ; Laval, S.H.* ; Maxwell, S.* ; Cossins, J.* ; Krause, S.* ; Muelas, N.* ; Vilchez, J.J.* ; Colomer, J.* ; Mallebrera, C.J.* ; Nascimento, A.* ; Nafissi, S.* ; Kariminejad, A.* ; Nilipour, Y.* ; Bozorgmehr, B.* ; Najmabadi, H.* ; Rodolico, C.* ; Sieb, J.P.* ; Steinlein, O.K.* ; 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.*

Hexosamine biosynthetic pathway mutations cause neuromuscular transmission defect.

Am. J. Hum. Genet. 88, 162-172 (2011)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Neuromuscular junctions (NMJs) are synapses that transmit impulses from motor neurons to skeletal muscle fibers leading to muscle contraction. Study of hereditary disorders of neuromuscular transmission, termed congenital myasthenic syndromes (CMS), has helped elucidate fundamental processes influencing development and function of the nerve-muscle synapse. Using genetic linkage, we find 18 different biallelic mutations in the gene encoding glutamine-fructose-6-phosphate transaminase 1 (GFPT1) in 13 unrelated families with an autosomal recessive CMS. Consistent with these data, downregulation of the GFPT1 ortholog gfpt1 in zebrafish embryos altered muscle fiber morphology and impaired neuromuscular junction development. GFPT1 is the key enzyme of the hexosamine pathway yielding the amino sugar UDP-N-acetylglucosamine, an essential substrate for protein glycosylation. Our findings provide further impetus to study the glycobiology of NMJ and synapses in general.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Congenital myasthenicc syndromes; Limb-girdle myastenia; Nucleocytoplasmic proteins; Acetylcholine-receptor; N-acetyglucosamine; Linkage analysis; Messenger-RNA; O-glcnac; Muscle; Glycosylation
ISSN (print) / ISBN 0002-9297
e-ISSN 1537-6605
Journal American Journal of Human Genetics, The
Quellenangaben Volume: 88, Issue: 2, Pages: 162-172 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place New York, NY
Reviewing status Peer reviewed
Institute(s) Institute of Human Genetics (IHG)