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Missense variant c.1460 T > C (p.L487P) enhances protein degradation of ER mannosyltransferase ALG9 in two new ALG9-CDG patients presenting with West syndrome and review of the literature

ALG9-CDG is a CDG-I defect within the group of Congenital Disorders of Glycosylation (CDG). We here describe the clinical symptoms of two new and unrelated ALG9-CDG patients, both carrying the novel homozygous missense variant c.1460 T > C (p.L487P) in the ALG9 gene which led to global developmen...

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Autori principali: Himmelreich, Nastassja (Autore) , Dimitrov, Bianca (Autore) , Zielonka, Matthias (Autore) , Hüllen, Andreas (Autore) , Hoffmann, Georg F. (Autore) , Juenger, Hendrik (Autore) , Müller, Herbert (Autore) , Lorenz, Imke (Autore) , Busse, Birgit (Autore) , Marschall, Christoph (Autore) , Schlüter, Gregor (Autore) , Thiel, Christian (Autore)
Natura: Article (Journal)
Lingua:inglese
Pubblicazione: 26 June 2022
In: Molecular genetics and metabolism
Year: 2022, Volume: 136, Fascicolo: 4, Pages: 274-281
ISSN:1096-7206
DOI:10.1016/j.ymgme.2022.06.005
Accesso online:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.ymgme.2022.06.005
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S1096719222003547
Testo
Note sull'autore:Nastassja Himmelreich, Bianca Dimitrov, Matthias Zielonka, Andreas Hüllen, Georg Friedrich Hoffmann, Hendrik Juenger, Herbert Müller, Imke Lorenz, Birgit Busse, Christoph Marschall, Gregor Schlüter, Christian Thiel
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Riassunto:ALG9-CDG is a CDG-I defect within the group of Congenital Disorders of Glycosylation (CDG). We here describe the clinical symptoms of two new and unrelated ALG9-CDG patients, both carrying the novel homozygous missense variant c.1460 T > C (p.L487P) in the ALG9 gene which led to global developmental delay, psychomotor disability, facial dysmorphisms, brain and heart defects, hearing loss, hypotonia, as well as feeding problems. New clinical symptoms comprised West syndrome with hypsarrhythmia. Quantitative RT-PCR analysis revealed a significantly enhanced ALG9 mRNA transcript level, whereas the protein amount in fibroblasts was significantly reduced. This could be ascribed to a stronger degradation of the mutated ALG9 protein in patient fibroblasts. Lipid-linked oligosaccharide analysis showed an ALG9-CDG characteristic accumulation of Man6GlcNAc2-PP-dolichol and Man8GlcNAc2-PP-dolichol in patient cells. The clinical findings of our patients and of all previously published ALG9-CDG patients are brought together to further expand the knowledge about this rare N-glycosylation disorder. SYNOPSIS: Homozygosity for p.L487P in ALG9 causes protein degradation and leads to West syndrome.
Descrizione del documento:Gesehen am 28.08.2022
Descrizione fisica:Online Resource
ISSN:1096-7206
DOI:10.1016/j.ymgme.2022.06.005

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