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Identification of two novel variants in ALG11 causing congenital disorder of glycosylation.
- Source :
-
Seizure [Seizure] 2024 Oct; Vol. 121, pp. 235-242. Date of Electronic Publication: 2024 Jul 26. - Publication Year :
- 2024
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Abstract
- Background: Congenital disorders of glycosylation (CDG) represent a heterogeneous group of rare inherited metabolic disorders due to abnormalities in protein or lipid glycosylation pathways, affecting multiple systems, and frequently being accompanied by neurological symptoms. ALG11-CDG, also known as CDG-1p, arises from a deficiency in a specific mannosyltransferase encoded by the ALG11 gene. To date, only 17 cases have been documented, and these patients have prominent clinical phenotypes, including seizures, developmental delay, and microcephaly.<br />Methods: We describe a novel case of a four-month-old boy from a Chinese family exhibiting developmental delay, seizures, and microcephaly. Trio whole-exome sequencing (WES) and subsequent Sanger sequencing were employed to identify the potential genetic cause, and functional study was performed to evaluate the pathogenicity of genetic variant identified.<br />Results: Trio WES unveiled novel compound heterozygous variants: c.1307G>T (p.G436V) and c.1403G>A (p.R468H) within exon 4 of the ALG11 gene, inherited from the father and mother, respectively. Subsequent in vitro functional analysis revealed decreased stability of the mutant protein and concurrent hypoglycosylation of GP130, a hyperglycosylated protein.<br />Conclusions: Our findings not only expand the clinical and variant spectrum of ALG11-CDG, but also emphasize the importance of WES as a first-tier genetic test in determining the molecular diagnosis.<br />Competing Interests: Declaration of competing interest The authors declare that they have no competing interests.<br /> (Copyright © 2024. Published by Elsevier Ltd.)
Details
- Language :
- English
- ISSN :
- 1532-2688
- Volume :
- 121
- Database :
- MEDLINE
- Journal :
- Seizure
- Publication Type :
- Academic Journal
- Accession number :
- 39260222
- Full Text :
- https://doi.org/10.1016/j.seizure.2024.07.020