Upstream SLC2A1 translation initiation causes GLUT1 deficiency syndrome.

Abstract

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.

• Authors: Michèl A Willemsen, Lisenka Elm Vissers, Marcel M Verbeek, Bregje W van Bon, Sinje Geuer, Christian Gilissen, Joerg Klepper, Michael P Kwint, Wilhelmina G Leen, Maartje Pennings, Ron A Wevers, Joris A Veltman, Erik-Jan Kamsteeg
• Journal: European journal of human genetics : EJHG (Eur J Hum Genet) Vol. 25 Issue 6 Pg. 771-774 (06 2017) ISSN: 1476-5438 [Electronic] England
• PMID: 28378819 (Publication Type: Journal Article)

Chemical References

• 5' Untranslated Regions
• Codon, Initiator
• Glucose Transporter Type 1
• Monosaccharide Transport Proteins
• SLC2A1 protein, human

Topics

• 5' Untranslated Regions
• Adolescent
• Carbohydrate Metabolism, Inborn Errors (diagnosis, genetics)
• Cells, Cultured
• Codon, Initiator (genetics)
• Female
• Glucose Transporter Type 1 (genetics, metabolism)
• Humans
• Monosaccharide Transport Proteins (deficiency, genetics)
• Mutation
• Peptide Chain Initiation, Translational