Novel variants and clinical symptoms in four new ALG3-CDG patients, review of the literature, and identification of AAGRP-ALG3 as a novel ALG3 variant with alanine and glycine-rich N-terminus
| Autor: | Lars Beedgen, Bianca Dimitrov, Gesche Düker, Matthias Zielonka, Michael J. Lentze, Catherine Barrey, Kai‐Christian Thiemann, Nathalie Seta, Rainer Ganschow, Stuart E.H. Moore, Verena Peters, Anna‐Marlen Hutter, Jonas Denecke, Irmgard Sinning, Georg F. Hoffmann, Christian Thiel, Sandrine Vuillaumier-Barrot, Thierry Dupré, Maximilian Breuer, Nastassja Himmelreich, Wolfgang Kölfen, Virginia Geiger, Andreas Hüllen, Andreas Ziegler |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Glycosylation Biology medicine.disease_cause Mannosyltransferases Polymorphism Single Nucleotide 03 medical and health sciences chemistry.chemical_compound Open Reading Frames Congenital Disorders of Glycosylation Polymorphism (computer science) Chlorocebus aethiops Genetics Macroglossia medicine Coding region Animals Humans Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase Genetics (clinical) Cells Cultured 030304 developmental biology 0303 health sciences Mutation 030305 genetics & heredity Intron Infant medicine.disease Molecular biology Open reading frame chemistry Child Preschool COS Cells Female medicine.symptom Congenital disorder of glycosylation |
| Zdroj: | Human mutation. 40(7) |
| ISSN: | 1098-1004 |
| Popis: | ALG3-CDG is one of the very rare types of congenital disorder of glycosylation (CDG) caused by variants in the ER-mannosyltransferase ALG3. Here, we summarize the clinical, biochemical, and genetic data of four new ALG3-CDG patients, who were identified by a type I pattern of serum transferrin and the accumulation of Man5 GlcNAc2 -PP-dolichol in LLO analysis. Additional clinical symptoms observed in our patients comprise sensorineural hearing loss, right-descending aorta, obstructive cardiomyopathy, macroglossia, and muscular hypertonia. We add four new biochemically confirmed variants to the list of ALG3-CDG inducing variants: c.350G>C (p.R117P), c.1263G>A (p.W421*), c.1037A>G (p.N346S), and the intron variant c.296+4A>G. Furthermore, in Patient 1 an additional open-reading frame of 141 bp (AAGRP) in the coding region of ALG3 was identified. Additionally, we show that control cells synthesize, to a minor degree, a hybrid protein composed of the polypeptide AAGRP and ALG3 (AAGRP-ALG3), while in Patient 1 expression of this hybrid protein is significantly increased due to the homozygous variant c.160_196del (g.165C>T). By reviewing the literature and combining our findings with previously published data, we further expand the knowledge of this rare glycosylation defect. |
| Databáze: | OpenAIRE |
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