{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T04:51:53Z","timestamp":1762059113508,"version":"build-2065373602"},"reference-count":24,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2022,7,17]],"date-time":"2022-07-17T00:00:00Z","timestamp":1658016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Foundation for Medical Research","award":["SPF20170938825"],"award-info":[{"award-number":["SPF20170938825"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This article describes the ocular phenotype associated with the identified Casitas B-lineage lymphoma (CBL) gene mutation and reviews the current literature. This work also includes the longitudinal follow-up of five unrelated cases of unexplained fundus lesions with visual loss associated with a history of hepatosplenomegaly. Wide repeated workup was made to rule out infections, inflammatory diseases, and lysosomal diseases. No variants in genes associated with retinitis pigmentosa, cone\u2013rod dystrophy, and inherited optic neuropathy were found. Molecular analysis was made using next-generation sequencing (NGS) and whole-exome sequencing (WES). The results included two cases sharing ophthalmological signs including chronic macular edema, vascular leakage, visual field narrowing, and electroretinography alteration. Two other cases showed damage to the optic nerve head and a fifth young patient exhibited bilateral complicated vitreoretinal traction and carried a heterozygous mutation in the CBL gene associated with a mutation in the IKAROS gene. Ruxolitinib as a treatment for RASopathy did not improve eye conditions, whereas systemic lesions were resolved in one patient. Mutations in the CBL gene were found in all five cases. In conclusion, a detailed description may pave the way for the CBL mutation ocular phenotype. Genetic analysis using whole-exome sequencing could be useful in the diagnosis of unusual clinical features.<\/jats:p>","DOI":"10.3390\/ijms23147868","type":"journal-article","created":{"date-parts":[[2022,7,17]],"date-time":"2022-07-17T22:57:06Z","timestamp":1658098626000},"page":"7868","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Casitas B-lineage lymphoma Gene Mutation Ocular Phenotype"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1935-2711","authenticated-orcid":false,"given":"Christine","family":"Fardeau","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Reference Center for Rare Diseases, La Piti\u00e9-Salp\u00eatri\u00e8re Hospital, Paris-Sorbonne University, 47-83 Boulevard de l\u2019H\u00f4pital, 75013 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6780-5714","authenticated-orcid":false,"given":"Munirah","family":"Alafaleq","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Reference Center for Rare Diseases, La Piti\u00e9-Salp\u00eatri\u00e8re Hospital, Paris-Sorbonne University, 47-83 Boulevard de l\u2019H\u00f4pital, 75013 Paris, France"},{"name":"Department of Ophthalmology, Imam Abdulrahman Bin Faisal University, Dammam 34212, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie-Ad\u00e9la\u00efde","family":"Ferchaud","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Reference Center for Rare Diseases, La Piti\u00e9-Salp\u00eatri\u00e8re Hospital, Paris-Sorbonne University, 47-83 Boulevard de l\u2019H\u00f4pital, 75013 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel","family":"Hi\u00e9","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, La Piti\u00e9-Salp\u00eatri\u00e8re Hospital, Paris-Sorbonne University, 47-83 Boulevard de l\u2019H\u00f4pital, 75013 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"Besnard","sequence":"additional","affiliation":[{"name":"Laboratory of Immunogenetics of Autoimmune Diseases in Children, INSERM UMR 1163, Imagine Institute, 24 Boulevard du Montparnasse, 75015 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5675-4624","authenticated-orcid":false,"given":"Sonia","family":"Meynier","sequence":"additional","affiliation":[{"name":"Laboratory of Immunogenetics of Autoimmune Diseases in Children, INSERM UMR 1163, Imagine Institute, 24 Boulevard du Montparnasse, 75015 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Rieux-Laucat","sequence":"additional","affiliation":[{"name":"Laboratory of Immunogenetics of Autoimmune Diseases in Children, INSERM UMR 1163, Imagine Institute, 24 Boulevard du Montparnasse, 75015 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Damien","family":"Roos-Weil","sequence":"additional","affiliation":[{"name":"Hematology Department, La Piti\u00e9-Salp\u00eatri\u00e8re Hospital, Paris-Sorbonne University, 47-83 Boulevard de l\u2019H\u00f4pital, 75013 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fleur","family":"Cohen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, La Piti\u00e9-Salp\u00eatri\u00e8re Hospital, Paris-Sorbonne University, 47-83 Boulevard de l\u2019H\u00f4pital, 75013 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabelle","family":"Meunier","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Reference Centre for Genetic Sensory Diseases, H\u00f4pital Gui de Chauliac, Montpellier University, 34295 Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1016\/S0140-6736(06)69740-7","article-title":"Retinitis pigmentosa","volume":"368","author":"Hartong","year":"2006","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1136\/bjo.2008.138560","article-title":"The prevalence of cystoid macular oedema in retinitis pigmentosa patients determined by optical coherence tomography","volume":"92","author":"Hajali","year":"2008","journal-title":"Br. J. Ophthalmol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1038\/eye.2016.115","article-title":"Uveitic macular oedema","volume":"30","author":"Fardeau","year":"2016","journal-title":"Eye"},{"key":"ref_4","first-page":"877","article-title":"The combination of whole-exome sequencing and clinical analysis allows better diagnosis of rare syndromic retinal dystrophies","volume":"97","author":"AlTalbishi","year":"2019","journal-title":"Acta Ophthalmol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1111\/ceo.13935","article-title":"Casitas B-lineage lymphoma mutation retinopathy mimicking uveitis","volume":"49","author":"Fardeau","year":"2021","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1136\/bjophthalmol-2016-309376","article-title":"Retinitis pigmentosa-associated cystoid macular oedema: Pathogenesis and avenues of intervention","volume":"101","author":"Strong","year":"2016","journal-title":"Br. J. Ophthalmol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1007\/s00417-017-3689-7","article-title":"Retinal pigmentary changes in chronic uveitis mimicking retinitis pigmentosa","volume":"255","author":"Sevgi","year":"2017","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1159\/000445063","article-title":"Optical Coherence Tomographic Analysis of Retina in Retinitis Pigmentosa Patients","volume":"56","author":"Liu","year":"2016","journal-title":"Ophthalmic Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/BF02133687","article-title":"Vitreous fluorophotometry studies in retinitis pigmentosa","volume":"222","author":"Travassos","year":"1985","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1080\/09273948.2017.1348527","article-title":"Uveitis in Patients with Retinitis Pigmentosa: 30 Years\u2019 Consecutive Data","volume":"26","author":"Majumder","year":"2018","journal-title":"Ocul. Immunol. Inflamm."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e5","DOI":"10.1016\/j.ophtha.2012.07.008","article-title":"Laboratory Evidence of Sustained Chronic Inflammatory Reaction in Retinitis Pigmentosa","volume":"120","author":"Yoshida","year":"2013","journal-title":"Ophthalmology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1111\/aos.13899","article-title":"Intraocular cytokine profile and autoimmune reactions in retinitis pigmentosa, age-related macular degeneration, glaucoma and cataract","volume":"97","author":"Fazil","year":"2019","journal-title":"Acta Ophthalmol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1038\/nature08240","article-title":"Gain of function of mutated C-CBL tumor suppressor in myeloid neoplasms","volume":"460","author":"Sanada","year":"2009","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"6182","DOI":"10.1182\/blood-2008-12-194548","article-title":"Frequent CBL mutations associated with 11q acquired uniparental disomy in myeloproliferative neoplasms","volume":"113","author":"Grand","year":"2009","journal-title":"Blood"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6109","DOI":"10.1200\/JCO.2009.23.7503","article-title":"Mutations of E3 Ubiquitin Ligase Cbl Family Members Constitute a Novel Common Pathogenic Lesion in Myeloid Malignancies","volume":"27","author":"Makishima","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1038\/ng.641","article-title":"Germline CBL mutations cause developmental abnormalities and predispose to juvenile myelomonocytic leukemia","volume":"42","author":"Niemeyer","year":"2010","journal-title":"Nat. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.ajhg.2010.06.015","article-title":"Heterozygous Germline Mutations in the CBL Tumor-Suppressor Gene Cause a Noonan Syndrome-like Phenotype","volume":"87","author":"Martinelli","year":"2010","journal-title":"Am. J. Hum. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1136\/jmg.2010.076836","article-title":"Germline mutations of the CBL gene define a new genetic syndrome with predisposition to juvenile myelomonocytic leukaemia","volume":"47","author":"Mechinaud","year":"2010","journal-title":"J. Med. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1002\/humu.22809","article-title":"Molecular diversity and associated phenotypic spectrum of germline CBL mutations","volume":"36","author":"Martinelli","year":"2015","journal-title":"Hum Mutat."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2404","DOI":"10.1038\/leu.2013.203","article-title":"In hematopoietic cells with a germline mutation of CBL, loss of heterozygosity is not a signature of juvenile myelo-monocytic leukemia","volume":"27","author":"Strullu","year":"2013","journal-title":"Leukemia"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1002\/ajmg.a.36838","article-title":"Hydrops, fetal pleural effusions and chylothorax in three patients with CBL mutations","volume":"167","author":"Lissewski","year":"2015","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1002\/pbc.25271","article-title":"Germline mutation of CBL is associated with moyamoya disease in a child with juvenile myelomonocytic leukemia and Noonan syndrome-like disorder","volume":"62","author":"Hyakuna","year":"2015","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1182\/blood-2013-10-533844","article-title":"Tracing the development of acute myeloid leukemia in CBL syndrome","volume":"123","author":"Becker","year":"2014","journal-title":"Blood"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Yang, X., Chung, J.-Y., Rai, U., and Esumi, N. (2018). Cadherins in the retinal pigment epithelium (RPE) revisited: P-cadherin is the highly dominant cadherin expressed in human and mouse RPE in vivo. 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