RGD Reference Report - Novel POMGNT1 point mutations and intragenic rearrangements associated with muscle-eye-brain disease. - Rat Genome Database
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Novel POMGNT1 point mutations and intragenic rearrangements associated with muscle-eye-brain disease.

Authors: Saredi, S  Ardissone, A  Ruggieri, A  Mottarelli, E  Farina, L  Rinaldi, R  Silvestri, E  Gandioli, C  D'Arrigo, S  Salerno, F  Morandi, L  Grammatico, P  Pantaleoni, C  Moroni, I  Mora, M 
Citation: Saredi S, etal., J Neurol Sci. 2012 Jul 15;318(1-2):45-50. doi: 10.1016/j.jns.2012.04.008. Epub 2012 May 2.
RGD ID: 11065512
Pubmed: (View Article at PubMed) PMID:22554691
DOI: Full-text: DOI:10.1016/j.jns.2012.04.008

Congenital muscular dystrophies due to defects in genes encoding proteins involved in alpha-dystroglycan (alpha-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 alpha-dystroglycan, have been associated with altered alpha-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 alpha-dystroglycanopathy phenotypes in children and foetuses, and hence for directing the genetic analysis.


Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Pomgnt1  (protein O-linked mannose N-acetylglucosaminyltransferase 1 (beta 1,2-))

Genes (Mus musculus)
Pomgnt1  (protein O-linked mannose beta 1,2-N-acetylglucosaminyltransferase)

Genes (Homo sapiens)
POMGNT1  (protein O-linked mannose N-acetylglucosaminyltransferase 1 (beta 1,2-))

Additional Information