Upstream SLC2A1 translation initiation causes GLUT1 deficiency syndrome

被引：20

作者：

Willemsen, Michel A. ^{[1
]}

Vissers, Lisenka E. L. M. ^{[2
]}

Verbeek, Marcel M. ^{[3
,4
]}

van Bon, Bregje W. ^{[2
]}

Geuer, Sinje ^{[2
]}

Gilissen, Christian ^{[2
]}

Klepper, Joerg ^{[5
]}

Kwint, Michael P. ^{[2
]}

Leen, Wilhelmina G. ^{[6
]}

Pennings, Maartje ^{[2
]}

Wevers, Ron A. ^{[4
]}

Veltman, Joris A. ^{[2
]}

Kamsteeg, Erik-Jan ^{[2
]}

机构：

[1] Radboud Univ Nijmegen, Med Ctr, Donders Ctr Brain Cognit & Behav, Dept Neurol Paediat Neurol, POB 9101, NL-6500 HB Nijmegen, Netherlands

[2] Radboud Univ Nijmegen, Med Ctr, Donders Ctr Brain Cognit & Behav, Dept Human Genet, Nijmegen, Netherlands

[3] Radboud Univ Nijmegen, Med Ctr, Dept Neurol, Nijmegen, Netherlands

[4] Radboud Univ Nijmegen, Med Ctr, Translat Metab Lab, Dept Lab Med, Nijmegen, Netherlands

[5] Childrens Hosp Aschaffenburg Alzenau, Aschaffenburg, Germany

[6] Canisius Wilhelmina Hosp, Dept Neurol, Nijmegen, Netherlands

来源：

EUROPEAN JOURNAL OF HUMAN GENETICS | 2017年 / 25卷 / 06期

关键词：

SEVERE INTELLECTUAL DISABILITY; BLOOD-BRAIN-BARRIER;

D O I：

10.1038/ejhg.2017.45

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：771 / 774

页数：4

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