Early onset or syndromic epilepsy

Gene: OLA1

Green List (high evidence)

Comment on list classification: There are 6 unrelated individuals reported with biallelic OLA1 variants and early onset seizures. Hence, this gene should be promoted to Green on Early onset or syndromic epilepsy.

Created: 7 Apr 2026, 9:09 a.m. | Last Modified: 7 Apr 2026, 9:09 a.m.

Panel Version: 8.175

PMID: 41887223 Alabdi et al., 2026
14 individuals from 9 families reported with homozygous loss of function variants in OLA1 with a phenotype characterised by a neurodevelopmental condition with connective tissue disorder.
All 14 individuals presented with intellectual disability / psychomotor delay. Seizures were reported in 6 unrelated individuals. Joint hypermobility was noted in 13/13 patients, 5 of them had skin laxity. 6 individuals had scoliosis or kyphoscoliosis. Several patients were diagnosed with Ehlers-Danos syndrome.
Microcephaly was noted in 4 individuals from unrelated families (severity details: -4.49 SD, -3SD, -4.6SD, and "HC 45cm at 9 years")

Functional evidence: C. elegans model with knock-in protein-truncating variants showed behavioural abnormalities (reduced bending, no response to touch), and reduced axon numbers in GABAergic neurons.
Variant in family 1 (p.Arg143Ter) was shown to cause complete loss of OLA1 protein on Western blot; RT-PCR was supportive of NMD taking place. Splice variant seen in Family 8 (c.728+5G>A) was demonstrated to cause exon 7 skipping.
Sources: Literature

Created: 7 Apr 2026, 9:07 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Ehlers-Danlos syndrome, hypermobility type, MONDO:0007523; neurodevelopmental disorder,MONDO:0700092; microcephaly, MONDO:0001149

Publications

• 41887223