Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 3 (MDDGA3)
- POMGNT1 - protein O-linked mannose N-acetylglucosaminyltransferase 1 (beta 1,2-) (POMGNT1)
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A,3 (MDDGA3) currently include Muscle-eye-brain disease (MEB), and a more severe form, Walker-Warburg congenital muscular dystrophy. MDDGA is genetically heterogeneous and can be caused by mutation in seven genes involved in DAG1 glycosylation: MDDGA2 (613150), caused by mutation in the POMT2 gene (607439) MDDGA3 (253280), caused by mutation in the POMGNT1 gene (606822) MDDGA4 (253800), caused by mutation in the FKTN gene (607440) MDDGA5 (613153), caused by mutation in the FKRP gene (606596) MDDGA6 (613154), caused by mutation in the LARGE gene (603590) MDDGA7 (614643), caused by mutation in the ISPD gene (614631) MDDGA8 (614830), caused by mutation in the GTDC2 gene (614828) MDDGA4 disease also includes Fukuyama congenital muscular dystrophy (FCMD). MDDGA3 is an autosomal recessive disease characterized by mental retardation, muscular dystrophy, retinal hypoplasia, brain abnormalities and early death. MDDGA3 disease belongs to the group of inherited congenital muscular dystrophies (CMDs).The MDDGA3 gene, POMGNT1, is a glycosylation enzyme that participates in the synthesis of O-mannosyl glycan, a modification that is rare in mammals but is known to be a laminin-binding ligand of -dystroglycan. Mutation in the POMGNT1 gene can also cause a less severe congenital muscular dystrophy-dystroglycanopathy with mental retardation (type B3; MDDGB3; 613151) and a limb-girdle muscular dystrophy-dystroglycanopathy (type C3; MDDGC3; 613157) A selective deficiency of -dystroglycan in MDDGA3 patients has been reported. Furthermore, brain-selective deletion of dystroglycan in mice is sufficient to cause CMD-like brain malformations. Dystroglycan-null brain loses its high-affinity binding to the extracellular matrix protein laminin, and shows discontinuities in the pial surface basal lamina (glia limitans) that probably underlie the neuronal migration errors. These findings suggest that -dystroglycan is a potential target of POMGNT1 and that altered glycosylation of -dystroglycan may play a critical role in the pathomechanism of MDDGA3. Diagnosis is based on the typical clinical picture and on the mutation detection in the POMGnT1 gene. A gene test also allows fetal diagnosis and carrier identification.
UMLS Concepts by OMIM 253280
C3151519 / MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE ANOMALIES), TYPE A, 3 / MDDGA3 / WALKER-WARBURG SYNDROME OR MUSCLE-EYE-BRAIN DISEASE, POMGNT1-RELATED
Other concept sources:
- Yoshida A, Kobayashi K, Manya H, Taniguchi K, Kano H, Mizuno M, Inazu T, Mitsuhashi H, Takahashi S, Takeuchi M, Herrmann R, Straub V, Talim B, Voit T, Topaloglu H, Toda T, Endo T. Muscular dystrophy and neuronal migration disorder caused by mutations in a glycosyltransferase, POMGnT1. Dev Cell. 2001 Nov;1(5):717-24. (Pubmed)
- Diesen C, Saarinen A, Pihko H, Rosenlew C, Cormand B, Dobyns WB, Dieguez J, Valanne L, Joensuu T, Lehesjoki AE. POMGnT1 mutation and phenotypic spectrum in muscle-eye-brain disease. J Med Genet. 2004 Oct;41(10):e115. No abstract available. (Pubmed)