Variant Synonymizer: Platform to identify mutations defined in different ways is available now!
Over 2,000 gene–disease validation summaries are now available—no login required!
OCEL1 has been proposed as a candidate gene for Aicardi syndrome (MONDO:0010568) following the identification of a de novo heterozygous c.499G>A (p.Ala167Thr) variant in a single female presenting with infantile spasms (HP:0012469) and agenesis of the corpus callosum (HP:0001274) (PMID:28361097). However, targeted sequencing of OCEL1 in 38 additional clinically well-characterized females with Aicardi syndrome failed to detect this or any other deleterious OCEL1 variants, suggesting the original finding may be an incidental observation (PMID:28361097). Segregation data are unavailable, and no additional probands with OCEL1 variants have been reported to date. No functional assays have been conducted to evaluate the impact of the p.Ala167Thr substitution on OCEL1 function. Overall, the genetic evidence is limited to a solitary case without replication, and the absence of supporting experimental data yields conflicting evidence for this gene-disease association. Key Take-home: OCEL1 is not recommended for routine diagnostic testing in Aicardi syndrome due to insufficient and conflicting evidence.
Gene–Disease AssociationDisputedInitial report of a single de novo OCEL1 variant (c.499G>A (p.Ala167Thr)) in Aicardi syndrome with no replication in 38 follow-up cases. Genetic EvidenceLimitedSingle case with de novo variant; absence of additional probands and no segregation data; variant not found in a 38-patient cohort ([PMID:28361097]). Functional EvidenceNo evidenceNo functional studies have been reported for OCEL1 variants in Aicardi syndrome. |