{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T02:55:03Z","timestamp":1780368903674,"version":"3.54.1"},"reference-count":65,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,9,22]],"date-time":"2023-09-22T00:00:00Z","timestamp":1695340800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto de Salud Carlos III (ISCIII)","award":["2020\/0197782"],"award-info":[{"award-number":["2020\/0197782"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Keratoconus is a corneal dystrophy that is one of the main causes of corneal transplantation and for which there is currently no effective treatment for all patients. The presentation of this disease in pediatric age is associated with rapid progression, a worse prognosis and, in 15\u201320% of cases, the need for corneal transplantation. It is a multifactorial disease with genetic variability, which makes its genetic study difficult. Discovering new therapeutic targets is necessary to improve the quality of life of patients. In this manuscript, we present the results of whole-exome sequencing (WES) of 24 pediatric families diagnosed at the University Hospital La Paz (HULP) in Madrid. The results show an oligogenic inheritance of the disease. Genes involved in the structure, function, cell adhesion, development and repair pathways of the cornea are proposed as candidate genes for the disease. Further studies are needed to confirm the involvement of the candidate genes described in this article in the development of pediatric keratoconus.<\/jats:p>","DOI":"10.3390\/genes14101838","type":"journal-article","created":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T10:40:22Z","timestamp":1695552022000},"page":"1838","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Whole-Exome Sequencing of 24 Spanish Families: Candidate Genes for Non-Syndromic Pediatric Keratoconus"],"prefix":"10.3390","volume":"14","author":[{"given":"Carmen","family":"Gonz\u00e1lez-Atienza","sequence":"first","affiliation":[{"name":"Molecular Ophthalmology Section, Medical and Molecular Genetics Institute (INGEMM) IdiPaz, Hospital Universitario La Paz, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elo\u00edsa","family":"S\u00e1nchez-Cazorla","sequence":"additional","affiliation":[{"name":"Molecular Ophthalmology Section, Medical and Molecular Genetics Institute (INGEMM) IdiPaz, Hospital Universitario La Paz, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Villoldo-Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Department of Pediatric Ophthalmology, IdiPaz, Hospital Universitario La Paz, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Almudena","family":"del Hierro","sequence":"additional","affiliation":[{"name":"Department of Pediatric Ophthalmology, IdiPaz, Hospital Universitario La Paz, 28046 Madrid, Spain"},{"name":"European Reference Network on Eye Diseases (ERN-EYE), Hospital Universitario La Paz, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9683-2025","authenticated-orcid":false,"given":"Ana","family":"Boto","sequence":"additional","affiliation":[{"name":"Department of Pediatric Ophthalmology, IdiPaz, Hospital Universitario La Paz, 28046 Madrid, Spain"},{"name":"European Reference Network on Eye Diseases (ERN-EYE), Hospital Universitario La Paz, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Guerrero-Carretero","sequence":"additional","affiliation":[{"name":"Department of Pediatric Ophthalmology, IdiPaz, Hospital Universitario La Paz, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6972-0880","authenticated-orcid":false,"given":"Mar\u00eda","family":"Nieves-Moreno","sequence":"additional","affiliation":[{"name":"Department of Pediatric Ophthalmology, IdiPaz, Hospital Universitario La Paz, 28046 Madrid, Spain"},{"name":"European Reference Network on Eye Diseases (ERN-EYE), Hospital Universitario La Paz, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8049-0238","authenticated-orcid":false,"given":"Natalia","family":"Arruti","sequence":"additional","affiliation":[{"name":"Department of Pediatric Ophthalmology, IdiPaz, Hospital Universitario La Paz, 28046 Madrid, Spain"},{"name":"European Reference Network on Eye Diseases (ERN-EYE), Hospital Universitario La Paz, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0118-5003","authenticated-orcid":false,"given":"Patricia","family":"Rodr\u00edguez-Solana","sequence":"additional","affiliation":[{"name":"Molecular Ophthalmology Section, Medical and Molecular Genetics Institute (INGEMM) IdiPaz, Hospital Universitario La Paz, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8887-7100","authenticated-orcid":false,"given":"Roc\u00edo","family":"Mena","sequence":"additional","affiliation":[{"name":"Molecular Ophthalmology Section, Medical and Molecular Genetics Institute (INGEMM) IdiPaz, Hospital Universitario La Paz, 28046 Madrid, Spain"},{"name":"Biomedical Research Center in the Rare Diseases Network (CIBERER), Carlos II Health Institute (ISCIII), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Rodr\u00edguez-Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Molecular Ophthalmology Section, Medical and Molecular Genetics Institute (INGEMM) IdiPaz, Hospital Universitario La Paz, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Rosa-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Department of Pediatric Ophthalmology, IdiPaz, Hospital Universitario La Paz, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Carlos","family":"Acal","sequence":"additional","affiliation":[{"name":"Department of Pediatric Ophthalmology, IdiPaz, Hospital Universitario La Paz, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joana","family":"Blasco","sequence":"additional","affiliation":[{"name":"Department of Pediatric Ophthalmology, IdiPaz, Hospital Universitario La Paz, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Naranjo-Castresana","sequence":"additional","affiliation":[{"name":"Department of Pediatric Ophthalmology, IdiPaz, Hospital Universitario La Paz, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Ruz-Caracuel","sequence":"additional","affiliation":[{"name":"Biomedical Research Center in the Rare Diseases Network (CIBERER), Carlos II Health Institute (ISCIII), 28029 Madrid, Spain"},{"name":"Clinical Bioinformatics Section, Medical and Molecular Genetics Institute (INGEMM) IdiPaz, CIBERER, Hospital Universitario La Paz, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria E. F.","family":"Monta\u00f1o","sequence":"additional","affiliation":[{"name":"Molecular Ophthalmology Section, Medical and Molecular Genetics Institute (INGEMM) IdiPaz, Hospital Universitario La Paz, 28046 Madrid, Spain"},{"name":"Biomedical Research Center in the Rare Diseases Network (CIBERER), Carlos II Health Institute (ISCIII), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Ortega Patr\u00f3n","sequence":"additional","affiliation":[{"name":"Molecular Ophthalmology Section, Medical and Molecular Genetics Institute (INGEMM) IdiPaz, Hospital Universitario La Paz, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Esther","family":"Rubio-Mart\u00edn","sequence":"additional","affiliation":[{"name":"Molecular Ophthalmology Section, Medical and Molecular Genetics Institute (INGEMM) IdiPaz, Hospital Universitario La Paz, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Garc\u00eda-Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Molecular Ophthalmology Section, Medical and Molecular Genetics Institute (INGEMM) IdiPaz, Hospital Universitario La Paz, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emi","family":"Rikeros-Orozco","sequence":"additional","affiliation":[{"name":"Biomedical Research Center in the Rare Diseases Network (CIBERER), Carlos II Health Institute (ISCIII), 28029 Madrid, Spain"},{"name":"Clinical Genetics Section, Medical and Molecular Genetics Institute (INGEMM) IdiPaz, CIBERER, Hospital Universitario La Paz, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda de Los \u00c1ngeles","family":"G\u00f3mez-Cano","sequence":"additional","affiliation":[{"name":"Clinical Genetics Section, Medical and Molecular Genetics Institute (INGEMM) IdiPaz, CIBERER, Hospital Universitario La Paz, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luna","family":"Delgado-Mora","sequence":"additional","affiliation":[{"name":"Biomedical Research Center in the Rare Diseases Network (CIBERER), Carlos II Health Institute (ISCIII), 28029 Madrid, Spain"},{"name":"Clinical Genetics Section, Medical and Molecular Genetics Institute (INGEMM) IdiPaz, CIBERER, Hospital Universitario La Paz, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4108-2383","authenticated-orcid":false,"given":"Susana","family":"Noval","sequence":"additional","affiliation":[{"name":"Department of Pediatric Ophthalmology, IdiPaz, Hospital Universitario La Paz, 28046 Madrid, Spain"},{"name":"European Reference Network on Eye Diseases (ERN-EYE), Hospital Universitario La Paz, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8080-8629","authenticated-orcid":false,"given":"Elena","family":"Vallesp\u00edn","sequence":"additional","affiliation":[{"name":"Molecular Ophthalmology Section, Medical and Molecular Genetics Institute (INGEMM) IdiPaz, Hospital Universitario La Paz, 28046 Madrid, Spain"},{"name":"European Reference Network on Eye Diseases (ERN-EYE), Hospital Universitario La Paz, 28046 Madrid, Spain"},{"name":"Biomedical Research Center in the Rare Diseases Network (CIBERER), Carlos II Health Institute (ISCIII), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1080\/13816810.2020.1868013","article-title":"Cascade of interactions between candidate genes reveals convergent mechanisms in keratoconus disease pathogenesis","volume":"42","author":"Veerappa","year":"2021","journal-title":"Ophthalmic Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"101559","DOI":"10.1016\/j.clae.2021.101559","article-title":"Keratoconus: An updated review","volume":"45","author":"Carracedo","year":"2022","journal-title":"Cont. 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