Hereditary spastic paraplegia

Gene: SLC2A1

Green List (high evidence)

SLC2A1 (solute carrier family 2 member 1)
EnsemblGeneIds (GRCh38): ENSG00000117394
EnsemblGeneIds (GRCh37): ENSG00000117394
OMIM: 138140, Gene2Phenotype
SLC2A1 is in 23 panels

3 reviews

Rebecca Foulger (Genomics England curator)

Comment on mode of inheritance: Although Biallelic MOI is suggested by the Reviewer Chris Buxton, PMIDs:27725288, 11136715 and 21832227 show autosomal dominant inheritance for the GLUT1 deficiency (including HSP phenotype). Therefore changed MOI to 'Monoallelic' as agreed with Arianna.
Created: 28 Jan 2019, 12:24 p.m.
Comment on list classification: Updated rating from Red to Green after review and advice from Arianna Tucci. Gene added to panel and rated Red by Chris Buxton, but sufficient cases of SLC2A1 variants and HSP phenotype from the literature to support causation.
Created: 28 Jan 2019, 12:23 p.m.
PMID:21832227 (Weber et al 2011) identified causative variants in SLC2A1 in a German/Dutch family and an Australian monozygotic twin pair with Dystonia. In their cohort of HSP patients, one missense variant (c.138G>C/p.Q46H) was detected in one case of German origin but functional studies indicated the variant was likely benign. The authors conclude that slowly progressive spastic paraparesis complicated by PED can therefore be regarded as a novel phenotype associated with SLC2A1 mutations. However, GLUT1 defects do not seem to play a major role in other forms of autosomal dominant HSP, as suggested by the absence of pathogenic mutations in 139 HSP index patients.
Created: 8 Jan 2019, 4:34 p.m.
PMID:27725288 (Diomedi et al., 2016) describe an Italian family where affected individuals presented with spastic paraplegia as a predominant symptom. Exome-sequencing study identified a p.Arg126Cys mutation in the SLC2A1 gene, encoding GLUT1, which segregated with the affected members of the family.
Created: 8 Jan 2019, 4:25 p.m.

Sarah Leigh (Genomics England Curator)

Comment on list classification: This gene is awaiting curator evaluation and rating.
Created: 19 Dec 2018, 2:12 p.m.

Chris Buxton (North Bristol NHS Trust)

Red List (low evidence)

Spastic diplegia described as a component phenotype with a more complex presentation
Klepper (2001, 11136715) described diplegic spasticity associated with other dev delay and seizure phenotype in sibs with a het GLUT1 variant. Weber (2011, 21832227) desribed childhood onset paroxysmal choreoathetosis and progressive spastic paraplegia and het varaints in SLC2A1.
Zorzi (2008, 18606970) described a 22yo Italian woman with het denovo missense in SLC2A1 with delayed psychomotor development, mild mental retardation, microcephaly, dysarthria, and spasticity.
Diagnostic on Sheffield HSP panel.
Sources: Literature
Created: 28 Nov 2018, 9:39 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Developmental delay; seizure; paroxysmal choreoathetosis; spastic paraplegia

Publications

History Filter Activity

28 Jan 2019, Gel status: 3

Set mode of inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for gene: SLC2A1 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

28 Jan 2019, Gel status: 3

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

Gene: slc2a1 has been classified as Green List (High Evidence).

28 Jan 2019, Gel status: 1

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for gene: SLC2A1 were changed from Developmental delay; seizure; paroxysmal choreoathetosis; spastic paraplegia to Developmental delay; seizure; paroxysmal choreoathetosis; spastic paraplegia; autosomal dominant, complicated hereditary spastic paraplegia (HSP)

8 Jan 2019, Gel status: 1

Set publications

Rebecca Foulger (Genomics England curator)

Publications for gene: SLC2A1 were set to 11136715; 21832227; 18606970

19 Dec 2018, Gel status: 1

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: slc2a1 has been classified as Red List (Low Evidence).

28 Nov 2018, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set penetrance

Chris Buxton (North Bristol NHS Trust)

gene: SLC2A1 was added gene: SLC2A1 was added to Hereditary spastic paraplegia. Sources: Literature Mode of inheritance for gene: SLC2A1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC2A1 were set to 11136715; 21832227; 18606970 Phenotypes for gene: SLC2A1 were set to Developmental delay; seizure; paroxysmal choreoathetosis; spastic paraplegia Penetrance for gene: SLC2A1 were set to unknown Review for gene: SLC2A1 was set to RED