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Intellectual disability v9.357 OLA1 Ida Ertmanska Tag Q1_26_promote_green was removed from gene: OLA1.
Tag Q2_26_promote_green tag was added to gene: OLA1.
Intellectual disability v9.357 OLA1 Ida Ertmanska Classified gene: OLA1 as Amber List (moderate evidence)
Intellectual disability v9.357 OLA1 Ida Ertmanska Added comment: Comment on list classification: There are 14 individuals reported from 9 unrelated families with biallelic variants in OLA1 and syndromic intellectual disability / psychomotor delay. Hence, this gene should be promoted to Green at the next update.
Intellectual disability v9.357 OLA1 Ida Ertmanska Gene: ola1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v9.356 OLA1 Ida Ertmanska gene: OLA1 was added
gene: OLA1 was added to Intellectual disability. Sources: Literature
Q1_26_promote_green tags were added to gene: OLA1.
Mode of inheritance for gene: OLA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OLA1 were set to 41887223
Phenotypes for gene: OLA1 were set to Ehlers-Danlos syndrome, hypermobility type, MONDO:0007523; neurodevelopmental disorder,MONDO:0700092; microcephaly, MONDO:0001149
Review for gene: OLA1 was set to GREEN
Added comment: 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
Intellectual disability v2.861 POLA1 Rebecca Foulger Classified gene: POLA1 as Green List (high evidence)
Intellectual disability v2.861 POLA1 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Red to Green based on additional 2019 paper provided by Konstantinos Varvagiannis. PMID:31006512 (Van Esch et al., 2019) report 9 additional males from 5 families hemizygous for POLA1. ID or DD was a feature in all patients (Table 1) and is seen alongside short stature, microcephaly and hypogonadism. The phenotype was distinct from the previously-reported XLPDR. Although the phenotype spectrum is broad for POLA1 variants, there are sufficient cases of ID/DD (>3 from PMID:31006512 and PMID:27019227, with ID/DD being a consistent phenotype in PMID:31006512 individuals), thereby warranting a Green rating.
Intellectual disability v2.861 POLA1 Rebecca Foulger Gene: pola1 has been classified as Green List (High Evidence).
Intellectual disability v2.860 POLA1 Rebecca Foulger Publications for gene: POLA1 were set to 15844784; 27019227; 19377476
Intellectual disability v2.859 POLA1 Rebecca Foulger Phenotypes for gene: POLA1 were changed from Pigmentary disorder, reticulate, with systemic manifestations, X-linked, 301220; XLPDR to Pigmentary disorder, reticulate, with systemic manifestations, X-linked, 301220; XLPDR; X-Linked Intellectual Disability associated with short stature, microcephaly, and hypogonadism
Intellectual disability v2.800 POLA1 Konstantinos Varvagiannis reviewed gene: POLA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31006512; Phenotypes: Global developmental delay, Intellectual disability, Microcephaly, Growth abnormality, Hypogonadism; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes