Upstream SLC2A1 translation initiation causes GLUT1 deficiency syndrome

Glucose transporter type 1 deficiency syndrome (GLUT1DS) is a neurometabolic disorder with a complex phenotypic spectrum but simple biomarkers in cerebrospinal fluid. The disorder is caused by impaired glucose transport into the brain resulting from variants in SCL2A1. In 10% of GLUT1DS patients, a...

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Bibliographic Details
Published in:European journal of human genetics : EJHG 2017-06, Vol.25 (6), p.771-774
Main Authors: Willemsen, Michèl A, Vissers, Lisenka Elm, Verbeek, Marcel M, van Bon, Bregje W, Geuer, Sinje, Gilissen, Christian, Klepper, Joerg, Kwint, Michael P, Leen, Wilhelmina G, Pennings, Maartje, Wevers, Ron A, Veltman, Joris A, Kamsteeg, Erik-Jan
Format: Article
Language:English
Subjects:
5' Untranslated Regions
Adolescent
Carbohydrate Metabolism, Inborn Errors - diagnosis
Carbohydrate Metabolism, Inborn Errors - genetics
Cells, Cultured
Cerebrospinal fluid
Codon, Initiator - genetics
Female
Genetic screening
Genomes
Glucose transport
Glucose transporter
Glucose Transporter Type 1 - genetics
Glucose Transporter Type 1 - metabolism
Humans
Metabolic disorders
Monosaccharide Transport Proteins - deficiency
Monosaccharide Transport Proteins - genetics
Mutation
Non-coding RNA
Peptide Chain Initiation, Translational
Short Report
Translation initiation
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Summary:Glucose transporter type 1 deficiency syndrome (GLUT1DS) is a neurometabolic disorder with a complex phenotypic spectrum but simple biomarkers in cerebrospinal fluid. The disorder is caused by impaired glucose transport into the brain resulting from variants in SCL2A1. In 10% of GLUT1DS patients, a genetic diagnosis can not be made. Using whole-genome sequencing, we identified a de novo 5'-UTR variant in SLC2A1, generating a novel translation initiation codon, severely compromising SLC2A1 function. This finding expands our understanding of the disease mechanisms underlying GLUT1DS and encourages further in-depth analysis of SLC2A1 non-coding regions in patients without variants in the coding region.
ISSN:1018-4813
1476-5438
DOI:10.1038/ejhg.2017.45