Ehlers Danlos syndrome with a likely monogenic cause

Gene: OLA1

Green List (high evidence)

Comment on list classification: There are 13 individuals reported from 9 unrelated families with biallelic variants in OLA1 and joint hypermobility, with additional features of skin laxity (5 cases) and scoliosis (6 cases), suggestive of EDS diagnosis. Hence, this gene should be promoted to Green at the next update.

Created: 1 Apr 2026, 10:17 a.m. | Last Modified: 1 Apr 2026, 10:17 a.m.

Panel Version: 4.8

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 unrelated 6 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: 1 Apr 2026, 10:12 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