B3GALNT2 gene

Overview

Gene (OMIM No.)
Function of gene/protein
  • Protein: beta-1,3-N-acetylgalactosaminyltransferase 2
  • An enzyme involved in the glycosylation (converting carbohydrates to glycoproteins) of alpha-dystroglycan DAG1
Clinical phenotype
(OMIM phenotype no.)
  • Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 11 (#615181)
  • Also known as Walker-Warburg syndrome (WWS)/Muscle Eye Brain Disease (MEB)
  • Defects in the glycosylation of alpha-dystroglycans cause 3 overlapping syndromes/dystroglycanopathies: WWS, MEB and Fukuyama type Congenital Muscular Dystrophy (FCMD; #253800)
  • WWS—most severe phenotype; MEB—intermediate phenotype; FCMD—mildest phenotype
  • Phenotype severity is determined by the extent which the mutation affects DAG1 glycosylation
Inheritance
  • Autosomal recessive
Ocular features
Systemic features
  • Congenital muscular dystrophy
  • Brain anomalies (cobblestone lissencephaly, hydrocephalus, hypoplastic cerebellar vermis, macrocephaly, microcephaly or anencephaly)
  • Severe hypotonia
  • Occasional seizures
  • Intellectual disability
  • Developmental delays
  • Patients with WWS have a severely limited lifespan with significant CNS and ocular anomalies
Key investigations
  • B-scan USS to measure axial length to document microphthalmia
  • Electrophysiology to determine visual potential
  • Gonioscopy (if tolerated/EUA) or anterior segment OCT to identify angle abnormalities and any associated anterior segment dysgenesis
  • MRI brain and orbit
  • Systemic assessment with a paediatrician and other relevant specialists
  • Bloods (elevated creatinine kinase)
  • Skeletal muscle biopsy
Molecular diagnosisNext generation sequencing
  • Targeted gene panels
  • Whole genome sequencing
ManagementOcularSystemic
  • Multidisciplinary approach
Therapies under research
  • None at present
Further information

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References

  1.  Stevens E, Carss KJ, Cirak S, et al. Mutations in B3GALNT2 Cause Congenital Muscular Dystrophy and Hypoglycosylation of a-Dystroglycan. Am J Hum Genet 2013; 92: 354–365
  2.  Yoshida-Moriguchi T, Willer T, Anderson ME, et al. SGK196 is a glycosylation-specific O-mannose kinase required for dystroglycan function. Science (80- ) 2013; 341: 896–899
  3.  Hiruma T, Togayachi A, Okamura K, et al. A Novel Human β1,3-N-Acetylgalactosaminyltransferase That Synthesizes A Unique Carbohydrate Structure, GalNAcβ1-3GlcNAc. J Biol Chem 2004; 279: 14087–14095
  4.  Francisco R, Pascoal C, Marques-da-Silva D, et al. Keeping an eye on congenital disorders of O-glycosylation: A systematic literature review. J Inherit Metab Dis. 2019;42(1):29-48

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Updated on November 30, 2020
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