{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:02:02Z","timestamp":1792789322705,"version":"4.5.0"},"reference-count":29,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012617","name":"Moorfields Eye Hospital NHS Foundation Trust","doi-asserted-by":"publisher","award":["BRC-D-CON 546795"],"award-info":[{"award-number":["BRC-D-CON 546795"]}],"id":[{"id":"10.13039\/501100012617","id-type":"DOI","asserted-by":"publisher"}]},{"award":["BRC-D-CON 546795"],"award-info":[{"award-number":["BRC-D-CON 546795"]}],"id":[{"id":"https:\/\/ror.org\/03zaddr67","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Moorfields Eye Charity","id":[{"id":"https:\/\/ror.org\/017hm5p20","id-type":"ROR","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/017hm5p20","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Ocular coloboma is a congenital eye defect with high genetic heterogeneity. This study investigated a four-generation pedigree to identify candidate variants underlying autosomal dominant iris and chorioretinal coloboma. Methods: Whole-exome sequencing (WES) was performed on a single affected family member. Variants were prioritised using the Phenopolis pipeline, filtered for rarity across multiple population databases, and retained where CADD indicated predicted deleteriousness. Candidate variants were then validated by Sanger sequencing in the four family members from whom DNA was available. Variants were classified according to ACMG\/AMP criteria. Results: Five rare heterozygous variants were identified: STOML1 (NM_004809.5:c.1100T&gt;C; p.(Leu367Pro)), MTIF2 (NM_002453.3:c.1337G&gt;A; p.(Trp446Ter)), CDH23 (NM_022124.6:c.8906G&gt;A; p.(Arg2969His)), CDON (NM_001378964.1:c.3276+1G&gt;T; p.?), and ERCC6L2 (NM_020207.7:c.19C&gt;T; p.(Gln7Ter)). Four are classified as of uncertain significance; the ERCC6L2 variant is classified as pathogenic in ClinVar. Conclusions: STOML1 is proposed as an exploratory candidate gene for isolated ocular coloboma, requiring replication in independent families and functional validation. The recurrent ERCC6L2 nonsense variant is reported as an incidental finding of potential haematological relevance.<\/jats:p>","DOI":"10.3390\/genes17091152","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T08:03:47Z","timestamp":1789977827000},"page":"1152","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["STOML1 as an Exploratory Candidate Gene for Autosomal Dominant Iris and Chorioretinal Coloboma in a British Family"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6008-8970","authenticated-orcid":false,"given":"Vanita","family":"Berry","sequence":"first","affiliation":[{"name":"UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK"},{"name":"Moorfields Eye Hospital NHS Foundation Trust, London EC1V 2PD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9545-7489","authenticated-orcid":false,"given":"Manav B.","family":"Ponnekanti","sequence":"additional","affiliation":[{"name":"UCL Medical School, University College London, 74 Huntley St, London WC1E 6DE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9514-559X","authenticated-orcid":false,"given":"Nancy","family":"Aychoua","sequence":"additional","affiliation":[{"name":"UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK"},{"name":"Moorfields Eye Hospital NHS Foundation Trust, London EC1V 2PD, UK"},{"name":"Oxford Eye Hospital NHS Foundation Trust, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6624-1518","authenticated-orcid":false,"given":"Maddy Ashwin","family":"Reddy","sequence":"additional","affiliation":[{"name":"Moorfields Eye Hospital NHS Foundation Trust, London EC1V 2PD, UK"},{"name":"Department of Ophthalmology, Royal London Hospital, Barts Health NHS Trust, Whitechapel Road, London E1 1FR, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Michaelides","sequence":"additional","affiliation":[{"name":"UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK"},{"name":"Moorfields Eye Hospital NHS Foundation Trust, London EC1V 2PD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/S0161-6420(99)00140-2","article-title":"Visual Acuity in Children with Coloboma","volume":"107","author":"Hornby","year":"2000","journal-title":"Ophthalmology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.ophtha.2011.07.039","article-title":"Anophthalmos, Microphthalmos, and Coloboma in the United Kingdom: Clinical Features, Results of Investigations, and Early Management","volume":"119","author":"Shah","year":"2012","journal-title":"Ophthalmology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"107940","DOI":"10.1016\/j.exer.2020.107940","article-title":"Genetics of Syndromic Ocular Coloboma: CHARGE and COACH Syndromes","volume":"193","author":"George","year":"2020","journal-title":"Exp. Eye Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1136\/jmg.2004.025494","article-title":"Ocular Coloboma: A Reassessment in the Age of Molecular Neuroscience","volume":"41","author":"Williams","year":"2004","journal-title":"J. Med. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1001\/archophthalmol.2010.320","article-title":"Incidence, Ocular Findings, and Systemic Associations of Ocular Coloboma: A Population-Based Study","volume":"129","author":"Nakamura","year":"2011","journal-title":"Arch. Ophthalmol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1001\/jamaophthalmol.2013.5305","article-title":"Microphthalmia, Anophthalmia, and Coloboma and Associated Ocular and Systemic Features: Understanding the Spectrum","volume":"131","author":"Skalicky","year":"2013","journal-title":"JAMA Ophthalmol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1179\/027249302125000193","article-title":"Environmental Risk Factors in Congenital Malformations of the Eye","volume":"22","author":"Hornby","year":"2002","journal-title":"Ann. Trop. Paediatr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1007\/s00439-019-02019-3","article-title":"An Update on the Genetics of Ocular Coloboma","volume":"138","author":"ALSomiry","year":"2019","journal-title":"Hum. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1002\/ajmg.c.31831","article-title":"Ocular Coloboma: Genetic Variants Reveal a Dynamic Model of Eye Development","volume":"184","author":"Yoon","year":"2020","journal-title":"Am. J. Med. Genet. C Semin. Med. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1002\/bdrc.21097","article-title":"Conserved Genetic Pathways Associated with Microphthalmia, Anophthalmia, and Coloboma","volume":"105","author":"Reis","year":"2015","journal-title":"Birth Defects Res. C Embryo Today"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Trejo-Reveles, V., Owen, N., Ching Chan, B.H., Toms, M., Schoenebeck, J.J., Moosajee, M., Rainger, J., and Genomics England Research Consortium (2023). Identification of Novel Coloboma Candidate Genes through Conserved Gene Expression Analyses across Four Vertebrate Species. Biomolecules, 13.","DOI":"10.3390\/biom13020293"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.ejmg.2014.05.002","article-title":"The Genetic Architecture of Microphthalmia, Anophthalmia and Coloboma","volume":"57","author":"Williamson","year":"2014","journal-title":"Eur. J. Med. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2421","DOI":"10.1093\/bioinformatics\/btx147","article-title":"Phenopolis: An Open Platform for Harmonization and Analysis of Genetic and Phenotypic Data","volume":"33","author":"Pontikos","year":"2017","journal-title":"Bioinformatics"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1016\/S0171-9335(99)80031-4","article-title":"Association of Stomatin with Lipid-Protein Complexes in the Plasma Membrane and the Endocytic Compartment","volume":"78","author":"Snyers","year":"1999","journal-title":"Eur. J. Cell Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"29218","DOI":"10.1074\/jbc.M109.014993","article-title":"Stomatin-like Protein-1 Interacts with Stomatin and Is Targeted to Late Endosomes","volume":"284","author":"Mairhofer","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1113\/jphysiol.2013.258657","article-title":"Subunit-Specific Inhibition of Acid Sensing Ion Channels by Stomatin-like Protein 1","volume":"592","author":"Kozlenkov","year":"2014","journal-title":"J. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"53886","DOI":"10.1074\/jbc.M407708200","article-title":"Stomatin Modulates Gating of Acid-Sensing Ion Channels","volume":"279","author":"Price","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S0167-4781(03)00144-1","article-title":"The Human Mitochondrial Translation Initiation Factor 2 Gene (MTIF2): Transcriptional Analysis and Identification of a Pseudogene","volume":"1628","author":"Overman","year":"2003","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1097\/ICU.0b013e328349419d","article-title":"Mitochondrial Disorders and the Eye","volume":"22","author":"Schrier","year":"2011","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Eells, J.T. (2019). Mitochondrial Dysfunction in the Aging Retina. Biology, 8.","DOI":"10.3390\/biology8020031"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2416","DOI":"10.1038\/s41433-023-02523-x","article-title":"Mitochondria and the Eye-Manifestations of Mitochondrial Diseases and Their Management","volume":"37","author":"Chen","year":"2023","journal-title":"Eye"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1042\/BST0360149","article-title":"Regulation of Cell-Cell Adhesion by the Cadherin-Catenin Complex","volume":"36","author":"Nelson","year":"2008","journal-title":"Biochem. Soc. Trans."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1167\/iovs.65.8.27","article-title":"CDH23-Associated Usher Syndrome: Clinical Features, Retinal Imaging, and Natural History","volume":"65","author":"Robson","year":"2024","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.ajhg.2011.07.001","article-title":"Mutations in CDON, Encoding a Hedgehog Receptor, Result in Holoprosencephaly and Defective Interactions with Other Hedgehog Receptors","volume":"89","author":"Bae","year":"2011","journal-title":"Am. J. Hum. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1111\/cge.13824","article-title":"Compound Heterozygous Splicing CDON Variants Result in Isolated Ocular Coloboma","volume":"98","author":"Reis","year":"2020","journal-title":"Clin. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.ajhg.2014.01.007","article-title":"ERCC6L2 Mutations Link a Distinct Bone-Marrow-Failure Syndrome to DNA Repair and Mitochondrial Function","volume":"94","author":"Tummala","year":"2014","journal-title":"Am. J. Hum. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e102","DOI":"10.1111\/bjh.19050","article-title":"First Description of Bone Marrow Failure Syndrome in Spain Caused by Mutations in the ERCC6L2 Gene","volume":"203","author":"Bandini","year":"2023","journal-title":"Br. J. Haematol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2505","DOI":"10.3892\/mmr.2017.6887","article-title":"Two Heterozygous Mutations Identified in One Chinese Patient with Bilateral Macular Coloboma","volume":"16","author":"Li","year":"2017","journal-title":"Mol. Med. Rep."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/9\/1152\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T04:43:20Z","timestamp":1790052200000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/9\/1152"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,20]]},"references-count":29,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["genes17091152"],"URL":"https:\/\/doi.org\/10.3390\/genes17091152","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,20]]}}}