{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T06:00:24Z","timestamp":1785218424127,"version":"3.55.0"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      <jats:italic>LRP5-<\/jats:italic>\n                      related retinal disease is classically associated with familial exudative vitreoretinopathy (FEVR), whereas biallelic inactivating variants cause osteoporosis-pseudoglioma syndrome. We report a severe congenital FEVR-like retinal dysplasia in a child carrying the novel heterozygous\n                      <jats:italic>LRP5<\/jats:italic>\n                      c.4462A\u2009&amp;gt;\u2009G (p.Ser1488Gly) variant of uncertain significance (VUS), adding carefully documented phenotypic layer to a ClinVar entry that has lacked disease-specific clinical context.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>\n                      A full-term female infant presented with nystagmus, absent visually directed behavior, and visual responsiveness limited to bright light. Examination under general anesthesia at 15 months revealed bilateral macular pseudocoloboma, mid-peripheral termination of retinal vascularization with avascular far peripheral retina, scattered pigment clumping, and microphthalmia. Optical coherence tomography showed marked outer retinal atrophy with an irregular V-shaped foveal contour, and electroretinography demonstrated non-detectable rod and cone responses. A targeted inherited retinal dystrophy panel identified the heterozygous\n                      <jats:italic>LRP5<\/jats:italic>\n                      c.4462A\u2009&amp;gt;\u2009G variant, absent from population databases and classified as a VUS. No pathogenic or likely pathogenic variants were found in other tested genes relevant to FEVR, Norrie disease spectrum, vitreoretinal dysplasia, microphthalmia-associated retinopathy, or early-onset retinal dystrophy. The variant was inherited from an asymptomatic father. No retinal intervention was indicated. Follow-up to 3 years showed no progression and no systemic features of\n                      <jats:italic>LRP5<\/jats:italic>\n                      -related bone disease.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The phenotype is best interpreted as an isolated, atypical FEVR-like congenital retinal dysplasia within\n                      <jats:italic>LRP5-<\/jats:italic>\n                      associated FEVR spectrum. However, paternal inheritance from an unaffected carrier, atypical severity, and lack of functional validation preclude definite causal assignment. This report supports cautious VUS interpretation and adds clinically relevant phenotypic evidence for future reinterpretation of LRP5 p.Ser1488Gly.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fped.2026.1912905","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T05:37:50Z","timestamp":1785217070000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Expanding the LRP5-phenotypic spectrum of the novel c.4462A\u2009&gt;\u2009G (p.Ser1488Gly) variant with isolated retinal involvement"],"prefix":"10.3389","volume":"14","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","place":["Zagreb, Croatia"]},{"name":"Faculty of Medicine, Josip Juraj Strossmayer University of Osijek","place":["Osijek, Croatia"]},{"name":"Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek","place":["Osijek, Croatia"]},{"name":"University Department of Nursing of the Catholic University of Croatia","place":["Zagreb, Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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 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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","place":["Zagreb, Croatia"]},{"name":"Faculty of Medicine, Josip Juraj Strossmayer University of Osijek","place":["Osijek, Croatia"]},{"name":"Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek","place":["Osijek, Croatia"]},{"name":"University Department of Nursing of the Catholic University of Croatia","place":["Zagreb, 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","place":["Zagreb, 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