Defective LARGE causes MDDGA6 and MDDGB6

Stable Identifier
R-HSA-5083627
Type
Pathway
Species
Homo sapiens
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Glycosyltransferase-like protein LARGE (MIM:603590) is a bifunctional glycosyltransferase with both xylosyltransferase and beta-1,3-glucuronyltransferase activities involved in the biosynthesis of a phosphorylated O-mannosyl trisaccharide, a structure present in alpha-dystroglycan (DAG1; MIM:128239) which plays a key role in skeletal muscle function and regeneration. LARGE contains two substrate-specific GT-domains and belongs to the CAZy glycosyltransferase families GT8 and GT49. Defects in LARGE result in hypoglycosylation of DAG1 and cause several congenital muscular dystrophies (CMDs). Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A6 (MDDGA6; MIM:613154) is associated with brain anomalies, eye malformations, profound mental retardation, and death usually in the first years of life (Clement et al. 2008, Mercuri et al. 2009). Muscular dystrophy-dystroglycanopathy congenital with mental retardation B6 (MDDGB6; MIM:608840) is associated with profound mental retardation, white matter changes and structural brain abnormalities (Longman et al. 2003).

Literature References
PubMed ID Title Journal Year
19067344 Brain involvement in muscular dystrophies with defective dystroglycan glycosylation

Clement, E, Mercuri, E, Godfrey, C, Smith, J, Robb, S, Kinali, M, Straub, V, Bushby, K, Manzur, A, Talim, B, Cowan, F, Quinlivan, R, Klein, A, Longman, C, McWilliam, R, Topaloglu, H, Mein, R, Abbs, S, North, K, Barkovich, AJ, Rutherford, M, Muntoni, F

Ann. Neurol. 2008
19299310 Congenital muscular dystrophies with defective glycosylation of dystroglycan: a population study

Mercuri, E, Messina, S, Bruno, C, Mora, M, Pegoraro, E, Comi, GP, D'Amico, A, Aiello, C, Biancheri, R, Berardinelli, A, Boffi, P, Cassandrini, D, Laverda, A, Moggio, M, Morandi, L, Moroni, I, Pane, M, Pezzani, R, Pichiecchio, A, Pini, A, Minetti, C, Mongini, T, Mottarelli, E, Ricci, E, Ruggieri, A, Saredi, S, Scuderi, C, Tessa, A, Toscano, A, Tortorella, G, Trevisan, CP, Uggetti, C, Vasco, G, Santorelli, FM, Bertini, E

Neurology 2009
12966029 Mutations in the human LARGE gene cause MDC1D, a novel form of congenital muscular dystrophy with severe mental retardation and abnormal glycosylation of alpha-dystroglycan

Longman, C, Brockington, M, Torelli, S, Jimenez-Mallebrera, C, Kennedy, C, Khalil, N, Feng, L, Saran, RK, Voit, T, Merlini, L, Sewry, CA, Brown, SC, Muntoni, F

Hum. Mol. Genet. 2003
Participants
Participant Of
Disease
Name Identifier Synonyms
congenital muscular dystrophy 0050557
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