Background The dysfunction of OPA1, a dynamin GTPase involved in mitochondrial fusion, is responsible for a large spectrum of neurological disorders, each of which includes optic neuropathy. The database dedicated to OPA1 ( https://www.lovd.nl/OPA1 ), created in 2005, has now evolved towards a centralized and more reliable database using the Global Variome shared Leiden Open-source Variation Database (LOVD) installation. Results The updated OPA1 database, which registers all the patients from our center as well as those reported in the literature, now covers a total of 831 patients: 697 with isolated dominant optic atrophy (DOA), 47 with DOA “plus”, and 83 with asymptomatic or unclassified DOA. It comprises 516 unique OPA1 variants, of which more than 80% (414) are considered pathogenic. Full clinical data for 118 patients are documented using the Human Phenotype Ontology, a standard vocabulary for referencing phenotypic abnormalities. Contributors may now make online submissions of phenotypes related to OPA1 mutations, giving clinical and molecular descriptions together with detailed ophthalmological and neurological data, according to an international thesaurus. Conclusions The evolution of the OPA1 database towards the LOVD, using unified nomenclature, should ensure its interoperability with other databases and prove useful for molecular diagnoses based on gene-panel sequencing, large-scale mutation statistics, and genotype-phenotype correlations.

Autosomal-dominant optic atrophy (ADOA) is the most common inherited optic neuropathy, due to mutations in the optic atrophy 1 gene (OPA1) in about 60%-80% of cases. At present, the clinical heterogeneity of patients carrying OPA1 variants renders genotype-phenotype correlations difficulty. Since 2005, when we published the first locus-specific database (LSDB) dedicated to OPA1, a large amount of new clinical and genetic knowledge has emerged, prompting us to update this database. We have used the Leiden Open-Source Variation Database to develop a clinico-biological database, aiming to add clinical phenotypes related to OPA1 variants. As a first step, we validated this new database by registering several patients previously reported in the literature, as well as new patients from our own institution. Contributors may now make online submissions of clinical and molecular descriptions of phenotypes due to OPA1 variants, including detailed ophthalmological and neurological data, with due respect to patient anonymity. The updated OPA1 LSDB (http://opa1.mitodyn.org/) should prove useful for molecular diagnoses, large-scale variant statistics, and genotype-phenotype correlations in ADOA studies.

ObjectiveWhat is the proportion of antibodies to myelin oligodendrocyte glycoprotein (MOG-Ab) in optic neuritis (ON) in adults and what would be the ON presentation for which MOG-Ab should be tested?MethodsMulticentric prospective study conducted during 1 year on all patients diagnosed with acute ON in all ophthalmological units in hospitals in a region in western France.ResultsSixty-five patients were included. MOG-Ab prevalence was 14% (9/65) during an acute ON and 13% (7/55) after exclusion of patients already diagnosed with multiple sclerosis (MS) (8) or MOG+ON (2). Compared with MS and clinically isolated syndrome, MOG+ON had no female preponderance (67% of men in case of MOG+ON and 22% of men in case of MS and clinically isolated syndrome, p<0.05) were more often bilateral (44% vs 3%, p<0.005) and associated with optic disc swelling (ODS) (78% vs 14%, p<0.001). To predict MOG+ON, the positive predictive values (PPVs) of male sex, ODS and bilateral involvement were 29% (95% CI 9% to 48%), 41% (95% CI 18% to 65%) and 40% (95% CI 10% to 70%), respectively, while the negative predictive values (NPV) were 93% (95% CI 86% to 100%), 96% (95% CI 90% to 100%) and 91% (95% CI 83% to 99%), respectively. The combined factor ‘ODS or bilateral or recurrent ON’ was the best compromise between PPV (31% (95% CI 14% to 48%)) and NPV (100% (95% CI 100% to 100%)).ConclusionAmong ON episodes, MOG-Ab were found in 14% of cases. MOG+ON occurred without female preponderance and was significantly associated with ODS and/or bilateral ON. Testing MOG-Ab only in patients presenting with ODS or bilateral or recurrent ON would limit MOG-Ab tests to fewer than half of all patients without the risk of missing any MOG+ON cases.