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.
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We thank the patients and their parents, as well as the referring physicians for their contributions to this study.
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JK has received speakers honoraria and travel costs from Nutricia GmbH, Eerlangen, Germany and Vitaflo Pharma GmbH, Bad Homburg, Germany. The remaining authors declare no conflict of interest.
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Willemsen, M., Vissers, L., Verbeek, M. et al. Upstream SLC2A1 translation initiation causes GLUT1 deficiency syndrome. Eur J Hum Genet 25, 771–774 (2017). https://doi.org/10.1038/ejhg.2017.45
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DOI: https://doi.org/10.1038/ejhg.2017.45
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