New GLUT-1 mutation in a child with treatment-resistant epilepsy

Slaughter, Laurel A.; Vartzelis, George; Arthur, Todd M.

doi:10.1016/j.eplepsyres.2009.01.004

Cited by 16 publications

(14 citation statements)

References 14 publications

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“…Of note, the patient-derived iPSCs also showed GLUT1 signal at the plasma membrane. This is consistent with the fact that only one GLUT1 allele in the patient is affected (Leen et al, 2010;Pascual et al, 2008;Slaughter et al, 2009). In summary, these data show that the mislocalization observed in HEK cells can be reproduced in patient cells.…”

Section: Figure 3 Recruitment Of Clathrin By Recurrent Gains Of Dilesupporting

confidence: 88%

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Mutations in Disordered Regions Can Cause Disease by Creating Dileucine Motifs

Meyer

Kirchner

Uyar

et al. 2018

Cell

105

110

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Many disease-causing missense mutations affect intrinsically disordered regions (IDRs) of proteins, but the molecular mechanism of their pathogenicity is enigmatic. Here, we employ a peptide-based proteomic screen to investigate the impact of mutations in IDRs on protein-protein interactions. We find that mutations in disordered cytosolic regions of three transmembrane proteins (GLUT1, ITPR1, and CACNA1H) lead to an increased clathrin binding. All three mutations create dileucine motifs known to mediate clathrin-dependent trafficking. Follow-up experiments on GLUT1 (SLC2A1), the glucose transporter causative of GLUT1 deficiency syndrome, revealed that the mutated protein mislocalizes to intracellular compartments. Mutant GLUT1 interacts with adaptor proteins (APs) in vitro, and knocking down AP-2 reverts the cellular mislocalization and restores glucose transport. A systematic analysis of other known disease-causing variants revealed a significant and specific overrepresentation of gained dileucine motifs in structurally disordered cytosolic domains of transmembrane proteins. Thus, several mutations in disordered regions appear to cause "dileucineopathies."

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Section: Figure 3 Recruitment Of Clathrin By Recurrent Gains Of Dilesupporting

confidence: 88%

“…P485L Mutation has been introduced by changing c.1454 C > T (Slaughter et al, 2009) with Q5â Site-Directed Mutagenesis Kit (NEB) Fw:CTGTTCCATCtCCTGGGGGCT, Rev:CTCCTCGGGTGTCTTGTCAC.…”

Section: Flp-in T-rex Glut1mentioning

confidence: 99%

Mutations in Disordered Regions Can Cause Disease by Creating Dileucine Motifs

Meyer

Kirchner

Uyar

et al. 2018

Cell

105

110

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“…Mutations in SLC2A1 are a well-know cause of glucose transporter-1 (GLUT1) deficiency (OMIM 606777), a severe disorder that results in acquired microcephaly, intractable epilepsy, developmental delay, and additional neurologi-cal manifestations (e.g., ataxia or movement disorders) (Klepper, 2011). However, in the last few years several observations have significantly expanded this phenotype to include variable age at onset and a wide spectrum of clinical manifestations, including refractory and early-onset absence seizures (Roulet-Perez et al, 2008;Suls et al, 2009;Slaughter et al, 2009;Mullen et al, 2010;Byrne et al, 2011;Klepper, 2011) and the same authors have demonstrated a permanent frontal hypometabolism in such patients (Suls et al, 2008). We failed to identify SLC2A1 mutations in the 20 screened patients, probably due to the fact that we did not identify children with additional neurological findings other than epilepsy.…”

Section: Discussionmentioning

confidence: 99%

A clinical and genetic study of 33 new cases with early-onset absence epilepsy

Giordano¹,

Accorsi²,

Galli³

et al. 2011

Epilepsy Research

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“…To date, 20 patients with GLUT1‐DS patients treated with MAD have been reported, including six patients treated only for movement disorders . Of eight patients for whom the outcome on epilepsy was published, four were reported to be seizure‐free after the start of the diet, three showed a reduction of seizure frequency of less than 90%, and one a reduction of seizure frequency of 70% . MAD has also been shown to be effective in paroxysmal movement disorders as well as continuous movement disorders such as ataxia, with an improvement in more than 50% of patients .…”

Section: Discussionmentioning

confidence: 99%

“…The modified Atkins diet (MAD) is now an established treatment for refractory childhood epilepsy, in addition to the ketogenic diet . However, few reports of the use of MAD in GLUT1‐DS cases are available ( n =20 patients) …”

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confidence: 99%