Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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 expression and normal expression of DPM3. This description emphasizes the large spectrum of symptoms characterizing CDG I patients.
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PMID:A new intronic mutation in the DPM1 gene is associated with a milder form of CDG Ie in two French siblings. 1664 Dec 2