ArticleMolecular genetics & genomic medicine2018
Protein modeling and clinical description of a novel in-frame GLB1 deletion causing GM1 gangliosidosis type II.
Article in Molecular genetics & genomic medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.
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Who cites it
5 citing papers in PubMed, 1 synthesis or guideline pooled it, 5 citations in OpenAlex.
- The natural history of Type 1 infantile GM1 gangliosidosis: A literature-based meta-analysis.Molecular genetics and metabolism · 2020Pooled it
- Article
- Molecular Modeling and Phenotypic Description of a Patient with a Novel Exonic Deletion ofMolecular syndromology · 2022Article
- Genomic Observations of a Rare/PathogenicMedicina (Kaunas, Lithuania) · 2019Article
- Protein modeling and clinical description of a novel in-frame GLB1 deletion causing GM1 gangliosidosis type II.Molecular genetics & genomic medicine · 2018Article
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBeta-galactosidase-1 (GLB1) is a lysosomal hydrolase that is responsible for breaking down specific glycoconjugates, particularly GM1 (monosialotetrahexosylganglioside). Pathogenic variants in GLB1 cause two different lysosomal storage disorders: GM1 gangliosidosis and mucopolysaccharidosis type IVB. In GM1 gangliosidosis, decreased β-galactosidase-1 enzymatic activity leads to the accumulation of GM1 gangliosides, predominantly within the CNS. We present a 22-month-old proband with GM1 gangliosidosis type II (late-infantile form) in whom a novel homozygous in-frame deletion (c.1468_1470delAAC, p.Asn490del) in GLB1 was detected.
methodsWe used an experimental protein structure of β-galactosidase-1 to generate a model of the p.Asn490del mutant and performed molecular dynamic simulations to determine whether this mutation leads to altered ligand positioning compared to the wild-type protein. In addition, residual mutant enzyme activity in patient leukocytes was evaluated using a fluorometric assay.
resultsMolecular dynamics simulations showed the deletion to alter the catalytic site leading to misalignment of the catalytic residues and loss of collective motion within the model. We predict this misalignment will lead to impaired catalysis of β-galactosidase-1 substrates. Enzyme assays confirmed diminished GLB1 enzymatic activity (~3% of normal activity) in the proband.
conclusionsWe have described a novel, pathogenic in-frame deletion of GLB1 in a patient with GM1 gangliosidosis type II.
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