{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T15:27:14Z","timestamp":1785252434078,"version":"3.55.0"},"reference-count":18,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T00:00:00Z","timestamp":1743638400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Disease-causing variants in the IDH3A gene are associated with autosomal recessive retinitis pigmentosa 90 (RP90) and Leber congenital amaurosis, with or without macular pseudocoloboma. Here, we report two patients: one compound heterozygous for IDH3A c.364G&gt;A, p.(Ala122Thr), which has conflicting classifications, and for IDH3A c.293C&gt;T, p.(Pro98Leu), which is likely pathogenic, and the other homozygous for IDH3A c.364G&gt;A, p.(Ala122Thr). This study is aimed at providing evidence to link the latter variants to a clinical phenotype. The first patient was a 6-year-old girl, and the second patient was a 29-year-old female. In both patients, the diagnostic assessments were consistent with the phenotype of RP, characterized by macular pseudocoloboma but of varying severity. Patients\u2019 phenotypes suggest that the c.293C&gt;T, p.(Pro98Leu) variant is linked to a more severe and extensive clinical phenotype, while the c.364G&gt;A, p.(Ala122Thr) variant results in a milder condition, primarily limited to retinal involvement. In Patient 2, the presence of both global and local stereopsis, indicating advanced visual development, suggests that the p.(Ala122Thr) missense variant may act as a hypomorphic allele which likely allows for some residual enzymatic activity of the IDH3A protein. This report highlights that macular pseudocoloboma can manifest even in the absence of a null variant. In contrast, more severe symptoms, such as mitochondrial encephalopathy, seem to be associated with the presence of a null allele. Furthermore, to the best of our knowledge, this is the first report of the IDH3A c.293C&gt;T, p.(Pro98Leu) variant.<\/jats:p>","DOI":"10.3390\/ijms26073364","type":"journal-article","created":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T06:52:56Z","timestamp":1743749576000},"page":"3364","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Unraveling the IDH3A: Expanding the Genotypic Spectrum of Macular Pseudocoloboma"],"prefix":"10.3390","volume":"26","author":[{"given":"Mirjana","family":"Bjelo\u0161","sequence":"first","affiliation":[{"name":"University Eye Department, Reference Center of the Ministry of Health of the Republic of Croatia for Pediatric Ophthalmology and Strabismus, Reference Center of the Ministry of Health of the Republic of Croatia for Inherited Retinal Dystrophies, Reference Center of the Ministry of Health of the Republic of Croatia for Standardized Echography in Ophthalmology, University Hospital \u201cSveti Duh\u201d, Sveti Duh 64, 10000 Zagreb, Croatia"},{"name":"Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Josipa Huttlera 4, 31000 Osijek, Croatia"},{"name":"Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, Crkvena 21, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3041-4186","authenticated-orcid":false,"given":"Ana","family":"\u0106uri\u0107","sequence":"additional","affiliation":[{"name":"University Eye Department, Reference Center of the Ministry of Health of the Republic of Croatia for Pediatric Ophthalmology and Strabismus, Reference Center of the Ministry of Health of the Republic of Croatia for Inherited Retinal Dystrophies, Reference Center of the Ministry of Health of the Republic of Croatia for Standardized Echography in Ophthalmology, University Hospital \u201cSveti Duh\u201d, Sveti Duh 64, 10000 Zagreb, Croatia"},{"name":"Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, Crkvena 21, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedict","family":"Rak","sequence":"additional","affiliation":[{"name":"University Eye Department, Reference Center of the Ministry of Health of the Republic of Croatia for Pediatric Ophthalmology and Strabismus, Reference Center of the Ministry of Health of the Republic of Croatia for Inherited Retinal Dystrophies, Reference Center of the Ministry of Health of the Republic of Croatia for Standardized Echography in Ophthalmology, University Hospital \u201cSveti Duh\u201d, Sveti Duh 64, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biljana","family":"Kuzmanovi\u0107 Elabjer","sequence":"additional","affiliation":[{"name":"University Eye Department, Reference Center of the Ministry of Health of the Republic of Croatia for Pediatric Ophthalmology and Strabismus, Reference Center of the Ministry of Health of the Republic of Croatia for Inherited Retinal Dystrophies, Reference Center of the Ministry of Health of the Republic of Croatia for Standardized Echography in Ophthalmology, University Hospital \u201cSveti Duh\u201d, Sveti Duh 64, 10000 Zagreb, Croatia"},{"name":"Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Josipa Huttlera 4, 31000 Osijek, Croatia"},{"name":"Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, Crkvena 21, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mladen","family":"Bu\u0161i\u0107","sequence":"additional","affiliation":[{"name":"University Eye Department, Reference Center of the Ministry of Health of the Republic of Croatia for Pediatric Ophthalmology and Strabismus, Reference Center of the Ministry of Health of the Republic of Croatia for Inherited Retinal Dystrophies, Reference Center of the Ministry of Health of the Republic of Croatia for Standardized Echography in Ophthalmology, University Hospital \u201cSveti Duh\u201d, Sveti Duh 64, 10000 Zagreb, Croatia"},{"name":"Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Josipa Huttlera 4, 31000 Osijek, Croatia"},{"name":"Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, Crkvena 21, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Ron\u010devi\u0107","sequence":"additional","affiliation":[{"name":"School of Medicine of the Catholic University of Croatia, Ilica 244, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/s10048-016-0507-z","article-title":"Homozygous mutation, p.Pro304His, in IDH3A, encoding isocitrate dehydrogenase 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