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

Journal of the Neurological Sciences
S SarediM Mora

Abstract

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 impo...Continue Reading

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Citations

Feb 26, 2016·Human Molecular Genetics·Mingchu XuRui Chen
Jan 20, 2016·Genetic Epidemiology·Li-Chu ChienYen-Feng Chiu
Nov 28, 2015·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Justin J-L WongJohn E J Rasko
Dec 3, 2014·Neuromuscular Disorders : NMD·Giovanni BaranelloMarina Mora
May 21, 2016·Clinical Genetics·D MassalskaT Roszkowski
Jul 16, 2013·The Journal of Craniofacial Surgery·Jin LanYongming Qiu
Feb 3, 2018·Journal of Inherited Metabolic Disease·R FranciscoVanessa Dos Reis Ferreira
Feb 12, 2019·Journal of Inherited Metabolic Disease·Rita FranciscoVanessa Dos Reis Ferreira
Sep 28, 2018·Frontiers in Psychiatry·Reem M A ShafiMagdalena Romanowicz

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Methods Mentioned

BETA
glycosylation
biopsy
PCR
cDNA

Software Mentioned

Rescue – ESE
Seqscape

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