A new intronic mutation in the DPM1 gene is associated with a milder form of CDG Ie in two French siblings

Pediatric Research
Julia DancourtStuart E H Moore

Abstract

Congenital disorders of glycosylation (CDG) type I (CDG I) are rare autosomal recessive diseases caused by deficiencies in the assembly of the dolichol-linked oligosaccharide (DLO) that is required for N-glycoprotein biosynthesis. CDG Ie is due to a defect in the synthesis of dolichyl-phosphoryl-mannose (Dol-P-Man), which is needed for DLO biosynthesis as well as for other glycosylation pathways. Human Dol-P-Man synthase is a heterotrimeric complex composed of DPM1p, DPM2p, and DPM3p, with DPM1p being the catalytic subunit. Here, we report two new CDG Ie patients who present milder symptoms than the five other CDG Ie patients described to date. The clinical pictures of the patients MS and his sister MT are dominated by major ataxia, with no notable hepatic involvement. MS cells accumulate the immature DLO species Dol-PP-GlcNAc2Man5 and possess only residual Dol-P-Man synthase activity. One homozygous intronic mutation, g.IVS4-5T>A, was found in the DPM1 gene, leading to exon skipping and transcription of a shortened transcript. Moreover, DPM1 expression was reduced by more than 90% in MS cells, in a nonsense-mediated mRNA decay (NMD)-independent manner. Full analysis of the DPM2 and DPM3 genes revealed a decrease in DPM2 expres...Continue Reading

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Citations

Jun 22, 2012·Glycoconjugate Journal·Michael Welti
Jan 26, 2008·Glycobiology·Isabelle Chantret, Stuart E H Moore
Feb 14, 2012·Biochimica Et Biophysica Acta·Dipak K Banerjee
Apr 15, 2016·American Journal of Medical Genetics. Part a·Hülya KayseriliRasim Özgür Rosti
Oct 2, 2014·Journal of Inherited Metabolic Disease·Anna BuczkowskaDirk J Lefeber
Apr 2, 2019·Journal of Inherited Metabolic Disease·Walinka van TolDirk J Lefeber
Nov 2, 2020·Molecular Genetics and Metabolism·Silvia RadenkovicEva Morava

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