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

S. Saredi, A. Ardissone, A. Ruggieri, E. Mottarelli, L. Farina, R. Rinaldi, E. Silvestri, C. Gandioli, S. D'Arrigo, F. Salerno, L. Morandi, P. Grammatico, C. Pantaleoni, I. Moroni, M. Mora

Research output: Contribution to journalArticlepeer-review


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.643 C > 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 + 1 G > 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.

Original languageEnglish
Pages (from-to)45-50
Number of pages6
JournalJournal of the Neurological Sciences
Issue number1-2
Publication statusPublished - Jul 15 2012


  • Alpha dystroglycan
  • Alpha-dystroglycanopathy
  • Congenital muscular dystrophy
  • Glycosylation
  • Glycosyltransferase
  • Muscle-eye-brain (MEB) disease
  • POMGnT1

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology


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