SLC2A1

• Haploinsufficiency score: 3
• Strength of Evidence (disclaimer): Sufficient evidence for dosage pathogenicity
• Haploinsufficiency Phenotype: GLUT1 DEFICIENCY SYNDROME 2; GLUT1DS2

Evidence for haploinsufficiency phenotype

PubMed ID	Description
10980529	Children presenting with infantile seizures, acquired microcephaly, and developmental delay were found to have novel heterozygous mutations in the GLUT1 (SLC2A1). Mutations included complete gene deletion, nonsense, splicing, frameshift and missense.
25532859	SLC2A1 mutations were found in 2 of 93 children with generalized epilepsy. One had a de novo deletion in exon 4 resulting in a premature stop with myoclonic atonic seizures, and the other (Patient 2), an inherited paternal missense mutation with idiopathic generalized epilepsy . The father of Patient 2 presented with paroxysmal excercise induced dyskinesia (PED) and no history of seizures. The monozygotic father's twin brother had epileptic seizures and PED. Causal mutations are most likely to be found in early onset absence epilepsy.
25564316	An Italian study found that sporadic GLUT1 deficiency tended to be more severe than familial mutations. The familial cases were all missense and the sporadic cases were both missense and frameshift/splicing or nonsense.

Haploinsufficiency phenotype comments:

PMID: 20129935 This paper describes the mutation spectrum of patients with GLUT1 deficiency. Multiple exon deletions were found in 11% of patients and these patients had the more severe, classical phenotype as compared to patients with missense mutations. Inactivating mutations were more likely to be associated with severe MR, movement disorder and early onset epilepsy. The authors recommend MLPA analysis for all suspected cases of GLUT1 deficiency.

• Triplosensitivity score: 0
• Strength of Evidence (disclaimer): No evidence for dosage pathogenicity