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POMGNT1 gene

Overview

Gene (OMIM No.)
Function of gene/protein
  • Protein: protein O-linked mannose N-acetylglucosaminyltransferase 1 (beta 1,2-)
  • POMGNT1 is important for glycosylation of alpha-dystroglycan (DAG1), which is important for maintaining tissue structure in skeletal muscles and the brain
  • POMGNT1 is found in a specialised structure called the Golgi apparatus, where proteins are modified
Clinical phenotype
(OMIM phenotype no.)
  • Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 3 (#253280)
  • Also known as Walker-Warburg syndrome (WWS)/Muscle Eye Brain Disease (MEB)
  • Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 3 (#613151)
  • Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 3 (#613157)
  • 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
  • Retinitis pigmentosa 76 (#617213)
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
  • Measurement of intraocular pressure
  • Gonioscopy (if tolerated/EUA) or anterior segment OCT to identify angle abnormalities and any associated anterior segment dysgenesis
  • Multimodal imaging using fundus autofluorescence (FAF) and OCT
  • 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.  Yoshida A, Kobayashi K, Manya H, et al. Muscular Dystrophy and Neuronal Migration Disorder Caused by Mutations in a Glycosyltransferase, POMGnT1. Dev Cell 2001; 1: 717–724
  2.  Kano H, Kobayashi K, Tachikawa M, et al. Deficiency of α-dystroglycan in muscle-eye-brain disease. Biochem Biophys Res Commun 2002; 291: 1283–1286
  3.  Teber S, Sezer T, Kafalı M, et al. Severe muscle–eye–brain disease is associated with a homozygous mutation in the POMGnT1 gene. Eur J Paediatr Neurol 2008; 12: 133–136
  4.  Raducu M, Baets J, Fano O, et al. Promoter alteration causes transcriptional repression of the POMGNT1 gene in limb-girdle muscular dystrophy type 2O. Eur J Hum Genet 2012; 20: 945–952
  5.  Godfrey C, Clement E, Mein R, et al. Refining genotype phenotype correlations in muscular dystrophies with defective glycosylation of dystroglycan. Brain 2007; 130: 2725–2735
  6.  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
  7.  Xu M, Yamada T, Sun Z, et al. Mutations in POMGNT1 cause non-syndromic retinitis pigmentosa. Hum Mol Genet. 2016;25(8):1479-1488
  8.  Wang NH, Chen SJ, Yang CF, et al. Homozygosity Mapping and Whole-Genome Sequencing Links a Missense Mutation in POMGNT1 to Autosomal Recessive Retinitis Pigmentosa. Invest Ophthalmol Vis Sci. 2016;57(8):3601-3609

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Updated on November 30, 2020
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