Evaluation of non-coding variation in GLUT1 deficiency

Yu-Chi Liu; Jia Wei Audrey Lee; Susannah T Bellows; John A Damiano; Saul A Mullen; Samuel F Berkovic; Melanie Bahlo; Ingrid E Scheffer; Michael S Hildebrand

Journal article

Evaluation of non-coding variation in GLUT1 deficiency

Yu-Chi Liu, Jia Wei Audrey Lee, Susannah T Bellows, John A Damiano, Saul A Mullen, Samuel F Berkovic, Melanie Bahlo, Ingrid E Scheffer, Michael S Hildebrand

DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY | WILEY-BLACKWELL | Published : 2016

DOI: 10.1111/dmcn.13163

Abstract

AIM: Loss-of-function mutations in SLC2A1, encoding glucose transporter-1 (GLUT-1), lead to dysfunction of glucose transport across the blood-brain barrier. Ten percent of cases with hypoglycorrhachia (fasting cerebrospinal fluid [CSF] glucose <2.2mmol/L) do not have mutations. We hypothesized that GLUT1 deficiency could be due to non-coding SLC2A1 variants. METHOD: We performed whole exome sequencing of one proband with a GLUT1 phenotype and hypoglycorrhachia negative for SLC2A1 sequencing and copy number variants. We studied a further 55 patients with different epilepsies and low CSF glucose who did not have exonic mutations or copy number variants. We sequenced non-coding promoter and int..

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University of Melbourne Researchers

Rick Leventer Author Paediatrics Royal Children's Hospital

Saul Mullen Author Medical Education

Ingrid Scheffer Author Medicine - Austin Health

Yu-Chi Liu Author Medical Biology (w.e.h.i.)

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Grants

Awarded by National Health and Medical Research Council (NHMRC)

Awarded by NHMRC

Funding Acknowledgements

We thank the patients and their families for participation in this study. Elena Aleksoska (Epilepsy Research Centre) is acknowledged for performing genomic DNA extractions. This study was supported by a National Health and Medical Research Council (NHMRC) Program Grant (628952) to SFB and IES, a Practitioner Fellowship (1006110) to IES and a Career Development Fellowship (1063799) to MSH. MB was supported by an NHMRC Senior Research Fellowship (1002098) and NHMRC Program Grant (1054618). This work was also supported by Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS funding to MB and YL. Authors report grant funds that contributed to this project as outlined above. IES discloses payments from UCB Pharma, Eisai, GSK, Athena Diagnostics, and Transgenomics for lectures and educational presentations, and a patent for SCN1A testing held by Bionomics Inc. licensed to various diagnostic companies. SFB discloses payments from UCB Pharma, Novartis Pharmaceuticals, Sanofi-Aventis, and Jansen Cilag for lectures and educational presentations, and a patent for SCN1A testing held by Bionomics Inc. licensed to various diagnostic companies.