Hereditary spastic paraplegiaGene: SLC2A1
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.
Comment on list classification: This gene is awaiting curator evaluation and rating.
Created: 19 Dec 2018, 2:12 p.m.
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.
Created: 28 Nov 2018, 9:39 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Developmental delay; seizure; paroxysmal choreoathetosis; spastic paraplegia
Mode of inheritance for gene: SLC2A1 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Gene: slc2a1 has been classified as Green List (High Evidence).
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)
Publications for gene: SLC2A1 were set to 11136715; 21832227; 18606970
Gene: slc2a1 has been classified as Red List (Low Evidence).
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