Novel POMGNT1 point mutations and intragenic rearrangements associated with muscle-eye-brain disease

J Neurol Sci. 2012 Jul 15;318(1-2):45-50. doi: 10.1016/j.jns.2012.04.008. Epub 2012 May 2.


Congenital muscular dystrophies due to defects in genes encoding proteins involved in α-dystroglycan (α-DG) glycosylation are a heterogeneous group of muscle disorders variably associated with central nervous system and eye abnormalities. One of the more severe is muscle-eye-brain disease (MEB). Mutations in genes coding for proven or putative glycosyltransferases (POMT1, POMT2, POMGnT1, fukutin, FKRP, and LARGE), the DPM3 gene encoding a DOL-P-Man synthase subunit, and the DAG1 gene encoding α-dystroglycan, have been associated with altered α-DG glycosylation. We report new POMGnT1 mutations and evaluate protein expression in 3 patients and 2 foetuses with variably severe MEB features. We identify two new point mutations (c.643C>T, c.1863delC), one new intragenic rearrangement (deletion of exons 2-8), and a new intron retention (between exons 21 and 22) resulting from a known point mutation c.1895+1G>T. Our study provides further evidence that rearrangements of the POMGnT1 gene are relatively common. Importantly, if heterozygous, they can be missed on standard genomic DNA sequencing. POMGNT1 protein analysis in 3 patients showed that the severity of the phenotype does not correlate with protein expression. Cerebral MRI is important for identifying MEB and α-dystroglycanopathy phenotypes in children and foetuses, and hence for directing the genetic analysis.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Fatal Outcome
  • Female
  • Fetal Diseases / diagnosis
  • Fetal Diseases / enzymology
  • Fetal Diseases / genetics
  • Gene Rearrangement / genetics
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Male
  • N-Acetylglucosaminyltransferases / genetics*
  • N-Acetylglucosaminyltransferases / metabolism*
  • Phenotype
  • Point Mutation / genetics
  • Pregnancy
  • Severity of Illness Index
  • Walker-Warburg Syndrome / diagnosis
  • Walker-Warburg Syndrome / enzymology*
  • Walker-Warburg Syndrome / genetics*


  • N-Acetylglucosaminyltransferases
  • protein O-mannose beta-1,2-N-acetylglucosaminyltransferase