RGD Reference Report - Paroxysmal choreoathetosis/spasticity (DYT9) is caused by a GLUT1 defect. - Rat Genome Database

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Paroxysmal choreoathetosis/spasticity (DYT9) is caused by a GLUT1 defect.

Authors: Weber, Y G  Kamm, C  Suls, A  Kempfle, J  Kotschet, K  Schüle, R  Wuttke, T V  Maljevic, S  Liebrich, J  Gasser, T  Ludolph, A C  Van Paesschen, W  Schöls, L  De Jonghe, P  Auburger, G  Lerche, H 
Citation: Weber YG, etal., Neurology. 2011 Sep 6;77(10):959-64. doi: 10.1212/WNL.0b013e31822e0479. Epub 2011 Aug 10.
RGD ID: 12879478
Pubmed: PMID:21832227   (View Abstract at PubMed)
DOI: DOI:10.1212/WNL.0b013e31822e0479   (Journal Full-text)


OBJECTIVE: Mutations in SLC2A1, encoding the glucose transporter type 1 (GLUT1), cause a broad spectrum of neurologic disorders including classic GLUT1 deficiency syndrome, paroxysmal exercise-induced dyskinesia (PED, DYT18), and absence epilepsy. A large German/Dutch pedigree has formerly been described as paroxysmal choreoathetosis/spasticity (DYT9) and linked close to but not including the SLC2A1 locus on chromosome 1p. We tested whether 1) progressive spastic paraparesis, in addition to PED, as described in DYT9, and 2) autosomal dominant forms of hereditary spastic paraparesis (HSP) without PED are caused by SLC2A1 defects.
METHODS: The German/Dutch family and an Australian monozygotic twin pair were clinically (re-)investigated, and 139 index cases with dominant or sporadic HSP in which relevant dominant genes were partially excluded were identified from databanks. SLC2A1 was sequenced in all cases in this observational study and the functional effects of identified sequence variations were tested in glucose uptake and protein expression assays.
RESULTS: We identified causative mutations in SLC2A1 in both families, which were absent in 400 control chromosomes, cosegregated with the affection status, and decreased glucose uptake in functional assays. In the 139 index patients with HSP without paroxysmal dyskinesias, we only identified one sequence variation, which, however, neither decreased glucose uptake nor altered protein expression.
CONCLUSIONS: This study shows that DYT9 and DYT18 are allelic disorders and enlarges the spectrum of GLUT1 phenotypes, now also including slowly progressive spastic paraparesis combined with PED. SLC2A1 mutations were excluded as a cause of HSP without PED in our cohort.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
dystonia 9  IAGP 12879478DNA:missense mutation:exon: p.R212C (c.634C>T) (human)RGD 
dystonia 9  ISOSLC2A1 (Homo sapiens)12879478; 12879478DNA:missense mutation:exon: p.R212C (c.634C>T) (human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Dyskinesia  IAGP 12879478DNA:missense mutation:exon: p.R212C (c.634C>T) RGD 
Objects Annotated

Genes (Rattus norvegicus)
Slc2a1  (solute carrier family 2 member 1)

Genes (Mus musculus)
Slc2a1  (solute carrier family 2 (facilitated glucose transporter), member 1)

Genes (Homo sapiens)
SLC2A1  (solute carrier family 2 member 1)


Additional Information