{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T07:14:26Z","timestamp":1768893266927,"version":"3.49.0"},"reference-count":50,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T00:00:00Z","timestamp":1747699200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust","award":["BRC-D-CON 546795"],"award-info":[{"award-number":["BRC-D-CON 546795"]}]},{"name":"UCL Institute of Ophthalmology","award":["BRC-D-CON 546795"],"award-info":[{"award-number":["BRC-D-CON 546795"]}]},{"name":"Moorfields Eye Charity","award":["BRC-D-CON 546795"],"award-info":[{"award-number":["BRC-D-CON 546795"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: This paper will identify the potential genetic causes of multimorbidity associated with autosomal dominant congenital cataract (ADCC). Methods: Whole exome sequencing (WES) was performed on 13 individuals affected with ADCC. Subsequent bioinformatic analyses identified variants with deleterious pathogenicity scores. Results: Disease-causing variants were identified in 8 genes already linked to cataract (CHMP4B, CRYAA, CRYBA1, CRYGD, CYP21A2, GJA8, OPA1, and POMGNT1), but variants previously associated with systemic disorders were also found in a further 11 genes (ACTL9, ALDH18A1, CBS, COL4A3, GALT, LRP5, NOD2, PCK2, POMT2, RSPH4A, and SMO). All variants were identified via pipeline data analysis, prioritising rare coding variants using Kaviar and the Genome Aggregation Database. The following ADCC-associated non-ocular phenotypes were identified in four patients in the cohort: (i) Horner\u2019s pupils, vaso-vagal syncope, and paroxysmal orthostatic tachycardia syndrome; (ii) reduced kidney function and high cholesterol; (iii) hypertension, high cholesterol, and kidney stones; and (iv) grade 1 spondylolysis. Conclusions: We report 11 novel genes identified in an ADCC patient cohort associated with systemic disorders found, along with 8 known cataract-causing genes. Our findings broaden the spectrum of potentially cataract-associated genes and their related lens phenotypes, as well as evidence multimorbidities in four patients, highlighting the importance of careful multisystem phenotyping following genetic analysis.<\/jats:p>","DOI":"10.3390\/genes16050604","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T11:50:31Z","timestamp":1747741831000},"page":"604","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Multimorbidity Through the Lens of the Eye: Pathogenic Variants for Multiple Systemic Disorders Found in an Autosomal Dominant Congenital Cataract Cohort"],"prefix":"10.3390","volume":"16","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":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex","family":"Ionides","sequence":"additional","affiliation":[{"name":"Moorfields Eye Hospital NHS Foundation Trust, London EC1V 2PD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chrysanthi","family":"Tsika","sequence":"additional","affiliation":[{"name":"Moorfields Eye Hospital NHS Foundation Trust, London EC1V 2PD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0644-4123","authenticated-orcid":false,"given":"Roy A.","family":"Quinlan","sequence":"additional","affiliation":[{"name":"Department of Biosciences, University of Durham, Durham DH1 3LE, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1136\/bjo.83.7.802","article-title":"Clinical and genetic heterogeneity in autosomal dominant cataract","volume":"83","author":"Ionides","year":"1999","journal-title":"Br. 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