POMT1 gene

Overview

Gene (OMIM No.)
Function of gene/protein
  • Protein: protein O-mannosyltransferase 1 (POMT1)
  • POMT1 is part of the POMT enzyme complex which is involved in the glycosylation of alpha-dystroglycan (DAG1)
  • DAG1 helps maintain tissue structure in skeletal muscles and the brain
Clinical phenotype
(OMIM phenotype no.)
  • Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1 (#236670)
  • Also known as Walker-Warburg syndrome (WWS)/Muscle Eye Brain Disease (MEB)
  • Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 1 (#613155)
  • Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 1 (#609308)
  • 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
  • Measurement of intraocular pressure
  • 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.  Manya H, Chiba A, Yoshida A, et al. Demonstration of mammalian protein O-mannosyltransferase activity: Coexpression of POMT1 and POMT2 required for enzymatic activity. Proc Natl Acad Sci U S A 2004; 101: 500–505
  2.  Akasaka-Manya K, Manya H, Endo T. Mutations of the POMT1 gene found in patients with Walker-Warburg syndrome lead to a defect of protein O-mannosylation. Biochem Biophys Res Commun 2004; 325: 75–79
  3.  Akasaka-Manya K, Manya H, Nakajima A, et al. Physical and functional association of human protein O-mannosyltransferases 1 and 2. J Biol Chem 2006; 281: 19339–19345
  4.  Beltrán-Valero De Bernabé D, Currier S, Steinbrecher A, et al. Mutations in the O-Mannosyltransferase Gene POMT1 Give Rise to the Severe Neuronal Migration Disorder Walker-Warburg Syndrome. Am J Hum Genet 2002; 71: 1033–1043
  5.  Kim DS, Hayashi YK, Matsumoto H, et al. POMT1 mutation results in defective glycosylation and loss of laminin-binding activity in alpha-DG. Neurology 2004; 62: 1009–1011
  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

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Updated on November 30, 2020
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