{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T19:14:44Z","timestamp":1789067684877,"version":"build-2803163510"},"reference-count":111,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2023,7,13]],"date-time":"2023-07-13T00:00:00Z","timestamp":1689206400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ONCE","award":["2020\/0197782"],"award-info":[{"award-number":["2020\/0197782"]}]},{"name":"ONCE","award":["18\/1234"],"award-info":[{"award-number":["18\/1234"]}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III (ISCIII)","doi-asserted-by":"publisher","award":["2020\/0197782"],"award-info":[{"award-number":["2020\/0197782"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III (ISCIII)","doi-asserted-by":"publisher","award":["18\/1234"],"award-info":[{"award-number":["18\/1234"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Non-syndromic pediatric cataracts are defined as opacification of the crystalline lens that occurs during the first years of life without affecting other organs. Given that this disease is one of the most frequent causes of reversible blindness in childhood, the main objective of this study was to propose new responsible gene candidates that would allow a more targeted genetic approach and expand our genetic knowledge about the disease. We present a whole exome sequencing (WES) study of 20 Spanish families with non-syndromic pediatric cataracts and a previous negative result on an ophthalmology next-generation sequencing panel. After ophthalmological evaluation and collection of peripheral blood samples from these families, WES was performed. We were able to reach a genetic diagnosis in 10% of the families analyzed and found genes that could cause pediatric cataracts in 35% of the cohort. Of the variants found, 18.2% were classified as pathogenic, 9% as likely pathogenic, and 72.8% as variants of uncertain significance. However, we did not find conclusive results in 55% of the families studied, which suggests further studies are needed. The results of this WES study allow us to propose LONP1, ACACA, TRPM1, CLIC5, HSPE1, ODF1, PIKFYVE, and CHMP4A as potential candidates to further investigate for their role in pediatric cataracts, and AQP5 and locus 2q37 as causal genes.<\/jats:p>","DOI":"10.3390\/ijms241411429","type":"journal-article","created":{"date-parts":[[2023,7,14]],"date-time":"2023-07-14T00:28:06Z","timestamp":1689294486000},"page":"11429","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Whole Exome Sequencing of 20 Spanish Families: Candidate Genes for Non-Syndromic Pediatric Cataracts"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0118-5003","authenticated-orcid":false,"given":"Patricia","family":"Rodr\u00edguez-Solana","sequence":"first","affiliation":[{"name":"Molecular Ophthalmology Section, Institute of Medical and Molecular Genetics (INGEMM), IdiPaz, La Paz University Hospital, 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, La Paz University Hospital, 28046 Madrid, Spain"},{"name":"European Reference Network on Eye Diseases (ERN-EYE), La Paz University Hospital, 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, La Paz University Hospital, 28046 Madrid, Spain"},{"name":"European Reference Network on Eye Diseases (ERN-EYE), La Paz University Hospital, 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, Institute of Medical and Molecular Genetics (INGEMM), IdiPaz, La Paz University Hospital, 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, Institute of Medical and Molecular Genetics (INGEMM), IdiPaz, La Paz University Hospital, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Guerrero-Carretero","sequence":"additional","affiliation":[{"name":"Department of Pediatric Ophthalmology, IdiPaz, La Paz University Hospital, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Carlos","family":"Acal","sequence":"additional","affiliation":[{"name":"Department of Pediatric Ophthalmology, IdiPaz, La Paz University Hospital, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joana","family":"Blasco","sequence":"additional","affiliation":[{"name":"Department of Pediatric Ophthalmology, IdiPaz, La Paz University Hospital, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas M.","family":"Peralta","sequence":"additional","affiliation":[{"name":"Department of Pediatric Ophthalmology, IdiPaz, La Paz University Hospital, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1ngela","family":"Del Pozo","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, Institute of Medical and Molecular Genetics (INGEMM), IdiPaz, CIBERER, La Paz University Hospital, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria E. F.","family":"Monta\u00f1o","sequence":"additional","affiliation":[{"name":"Molecular Ophthalmology Section, Institute of Medical and Molecular Genetics (INGEMM), IdiPaz, La Paz University Hospital, 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":"Luc\u00eda De","family":"Dios-Bl\u00e1zquez","sequence":"additional","affiliation":[{"name":"Clinical Bioinformatics Section, Institute of Medical and Molecular Genetics (INGEMM), IdiPaz, CIBERER, La Paz University Hospital, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3855-8021","authenticated-orcid":false,"given":"Celia","family":"Fern\u00e1ndez-Alcalde","sequence":"additional","affiliation":[{"name":"Department of Pediatric Ophthalmology, IdiPaz, La Paz University Hospital, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Gonz\u00e1lez-Atienza","sequence":"additional","affiliation":[{"name":"Molecular Ophthalmology Section, Institute of Medical and Molecular Genetics (INGEMM), IdiPaz, La Paz University Hospital, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elo\u00edsa","family":"S\u00e1nchez-Cazorla","sequence":"additional","affiliation":[{"name":"Molecular Ophthalmology Section, Institute of Medical and Molecular Genetics (INGEMM), IdiPaz, La Paz University Hospital, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda de Los \u00c1ngeles","family":"G\u00f3mez-Cano","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, Institute of Medical and Molecular Genetics (INGEMM), IdiPaz, CIBERER, La Paz University Hospital, 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, Institute of Medical and Molecular Genetics (INGEMM), IdiPaz, CIBERER, La Paz University Hospital, 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, La Paz University Hospital, 28046 Madrid, Spain"},{"name":"European Reference Network on Eye Diseases (ERN-EYE), La Paz University Hospital, 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, Institute of Medical and Molecular Genetics (INGEMM), IdiPaz, La Paz University Hospital, 28046 Madrid, Spain"},{"name":"European Reference Network on Eye Diseases (ERN-EYE), La Paz University Hospital, 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":[[2023,7,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/S0140-6736(17)30544-5","article-title":"Cataracts","volume":"390","author":"Liu","year":"2017","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.ejmg.2010.07.001","article-title":"Molecular characteristics of inherited congenital cataracts","volume":"53","author":"Huang","year":"2010","journal-title":"Eur. J. Med. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/bs.ctdb.2018.12.008","article-title":"Eye organogenesis: A hierarchical view of ocular development","volume":"132","author":"Miesfeld","year":"2019","journal-title":"Curr. Top. Dev. Biol."},{"key":"ref_4","first-page":"252","article-title":"Genetics of congenital cataract, its diagnosis and therapeutics","volume":"5","author":"Khan","year":"2018","journal-title":"Egypt. J. Basic Appl. Sci."},{"key":"ref_5","unstructured":"(2023, January 02). BioRender. Available online: https:\/\/biorender.com\/."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.semcdb.2007.10.003","article-title":"Congenital cataracts and their molecular genetics","volume":"19","author":"Hejtmancik","year":"2008","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.4103\/ijo.IJO_1023_17","article-title":"Paediatric cataract","volume":"65","author":"Khokhar","year":"2017","journal-title":"Indian J. Ophthalmol."},{"key":"ref_8","first-page":"178","article-title":"The etiology of congenital cataracts. A survey of 386 cases","volume":"6","author":"Merin","year":"1971","journal-title":"Can. J. Ophthalmol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1016\/j.survophthal.2022.03.005","article-title":"Current management of infantile cataracts","volume":"67","author":"Lenhart","year":"2022","journal-title":"Surv. Ophthalmol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"107872","DOI":"10.1016\/j.exer.2019.107872","article-title":"Molecular genetics of congenital cataracts","volume":"191","author":"Li","year":"2020","journal-title":"Exp. Eye Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"16425","DOI":"10.1074\/jbc.M313402200","article-title":"Binding of destabilized \u03b2B2-crystallin mutants to \u03b1-crystallin: The role of a folding intermediate","volume":"279","author":"Sathish","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Moreau, K.L., and King, J.A. (2012). Cataract-Causing Defect of a Mutant \u03b3-Crystallin Proceeds through an Aggregation Pathway which Bypasses Recognition by the \u03b1-Crystallin Chaperone. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0037256"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5369","DOI":"10.1167\/iovs.11-7168","article-title":"Overexpression of human \u03b3C-crystallin 5 bp duplication disrupts lens morphology in transgenic mice","volume":"52","author":"Ma","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.bbagen.2015.06.001","article-title":"Autophagy and UPR in alpha-crystallin mutant knock-in mouse models of hereditary cataracts","volume":"1860","author":"Andley","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.exer.2012.06.004","article-title":"The unfolded protein response is activated in connexin 50 mutant mouse lenses","volume":"102","author":"Alapure","year":"2012","journal-title":"Exp. Eye Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"17848","DOI":"10.1038\/s41598-017-18222-z","article-title":"Two novel mutations identified in ADCC families impair crystallin protein distribution and induce apoptosis in human lens epithelial cells","volume":"7","author":"Li","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1111\/j.1469-1809.1963.tb00782.x","article-title":"Probable linkage between a congenital cataract locus and the Duffy blood group locus","volume":"27","author":"Renwick","year":"1963","journal-title":"Ann. Hum. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Kandaswamy, D.K., Prakash, M.V.S., Graw, J., Koller, S., Magyar, I., Tiwari, A., Berger, W., and Santhiya, S.T. (2020). Application of WES towards molecular investigation of congenital cataracts: Identification of novel alleles and genes in a hospital-based cohort of south India. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21249569"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Sun, W., Xiao, X., Li, S., Guo, X., and Zhang, Q. (2014). Exome Sequencing of 18 Chinese Families with Congenital Cataracts: A New Sight of the NHS Gene. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0100455"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"108662","DOI":"10.1016\/j.exer.2021.108662","article-title":"Inherited cataracts: Genetic mechanisms and pathways new and old","volume":"209","author":"Shiels","year":"2021","journal-title":"Exp. Eye Res."},{"key":"ref_21","first-page":"2007","article-title":"Cat-Map: Putting cataract on the map","volume":"16","author":"Shiels","year":"2010","journal-title":"Mol. Vis."},{"key":"ref_22","first-page":"174","article-title":"Identification of a novel CRYBB2 missense mutation causing congenital autosomal dominant cataract","volume":"18","author":"Weisschuh","year":"2012","journal-title":"Mol. Vis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.exer.2008.10.011","article-title":"Genetics of crystallins: Cataract and beyond","volume":"88","author":"Graw","year":"2009","journal-title":"Exp. Eye Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/1479-7364-6-26","article-title":"The human crystallin gene families","volume":"6","author":"Wistow","year":"2012","journal-title":"Hum. Genom."},{"key":"ref_25","first-page":"1687","article-title":"sHSP in the eye lens: Crystallin mutations, cataract and proteostasis","volume":"44","author":"Clark","year":"2012","journal-title":"Am. J. Ophthalmol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/j.ajo.2007.08.005","article-title":"Recessive Congenital Total Cataract with Microcornea and Heterozygote Carrier Signs Caused by a Novel Missense CRYAA Mutation (R54C)","volume":"144","author":"Khan","year":"2007","journal-title":"Am. J. Ophthalmol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1016\/j.bbadis.2016.02.003","article-title":"Human \u03b2A3\/A1-crystallin splicing mutation causes cataracts by activating the unfolded protein response and inducing apoptosis in differentiating lens fiber cells","volume":"1862","author":"Ma","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"107371","DOI":"10.1016\/j.carpath.2021.107371","article-title":"Sengers syndrome: A rare case of cardiomyopathy combined with congenital cataracts in an infant: Post-mortem case report","volume":"54","author":"Fnon","year":"2021","journal-title":"Cardiovasc. Pathol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1038\/nature14650","article-title":"Lanosterol reverses protein aggregation in cataracts","volume":"523","author":"Zhao","year":"2015","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6774","DOI":"10.1167\/iovs.10-6579","article-title":"Juvenile Cataract-Associated Mutation of Solute Carrier SLC16A12 Impairs Trafficking of the Protein to the Plasma Membrane","volume":"52","author":"Castorino","year":"2011","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/j.ajhg.2018.09.004","article-title":"Bi-allelic Loss-of-Function Variants in DNMBP Cause Infantile Cataracts","volume":"103","author":"Ansar","year":"2018","journal-title":"Am. J. Hum. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Quan, Y., Du, Y., Tong, Y., Gu, S., and Jiang, J.X. (2021). Connexin Gap Junctions and Hemichannels in Modulating Lens Redox Homeostasis and Oxidative Stress in Cataractogenesis. Antioxidants, 10.","DOI":"10.3390\/antiox10091374"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Berthoud, V.M., Gao, J., Minogue, P.J., Jara, O., Mathias, R.T., and Beyer, E.C. (2020). Connexin Mutants Compromise the Lens Circulation and Cause Cataracts through Biomineralization. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21165822"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1007\/s00439-006-0319-6","article-title":"Autosomal recessive juvenile onset cataract associated with mutation in BFSP1","volume":"121","author":"Ramachandran","year":"2007","journal-title":"Hum. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5252","DOI":"10.1167\/iovs.03-0224","article-title":"Targeted deletion of the lens fiber cell-specific intermediate filament protein filensin","volume":"44","author":"Alizadeh","year":"2003","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Li, S., Zhang, J., Cao, Y., You, Y., and Zhao, X. (2019). Novel mutations identified in Chinese families with autosomal dominant congenital cataracts by targeted next-generation sequencing. BMC Med. Genet., 20.","DOI":"10.1186\/s12881-019-0933-5"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e001064","DOI":"10.1136\/bmjophth-2022-001064","article-title":"Pathogenic genetic variants identified in Australian families with paediatric cataract","volume":"7","author":"Jones","year":"2022","journal-title":"BMJ Open Ophthalmol."},{"key":"ref_38","unstructured":"(2023, March 08). Entry\u2014#611391\u2014Cataract 33, Multiple Types; Ctrct33\u2014Omim. Available online: https:\/\/www.omim.org\/entry\/611391."},{"key":"ref_39","unstructured":"(2023, March 08). Entry\u2014#611597\u2014Cataract 12, Multiple Types; Ctrct12\u2014Omim. Available online: https:\/\/www.omim.org\/entry\/611597."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Nieves-Moreno, M., Noval, S., Peralta, J., Palomares-Bralo, M., del Pozo, A., Garcia-Mi\u00f1aur, S., Santos-Simarro, F., and Vallespin, E. (2021). Expanding the Phenotypic Spectrum of PAX6 Mutations: From Congenital Cataracts to Nystagmus. Genes, 12.","DOI":"10.3390\/genes12050707"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Jarwar, P., Sheikh, S.A., Waryah, Y.M., Ujjan, I.U., Riazuddin, S., Waryah, A.M., and Ahmed, Z.M. (2021). Biallelic Variants in EPHA2 Identified in Three Large Inbred Families with Early-Onset Cataract. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221910655"},{"key":"ref_42","first-page":"1553","article-title":"Association of EPHA2 polymorphisms and age-related cortical cataract in a Han Chinese population","volume":"17","author":"Tan","year":"2011","journal-title":"Mol. Vis."},{"key":"ref_43","first-page":"334","article-title":"Mutations in FYCO1 identified in families with congenital cataracts","volume":"26","author":"Iqbal","year":"2020","journal-title":"Mol. Vis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e22801","DOI":"10.1096\/fj.202201368RR","article-title":"Charged multivesicular body protein 4b forms complexes with gap junction proteins during lens fiber cell differentiation","volume":"37","author":"Zhou","year":"2023","journal-title":"FASEB J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"974393","DOI":"10.1155\/2014\/974393","article-title":"Association of CHMP4B and Autophagy with Micronuclei: Implications for Cataract Formation","volume":"2014","author":"Sagona","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"713284","DOI":"10.3389\/fmed.2021.713284","article-title":"Broadening the Mutation Spectrum in GJA8 and CHMP4B: Novel Missense Variants and the Associated Phenotypes in Six Chinese Han Congenital Cataracts Families","volume":"8","author":"Wang","year":"2021","journal-title":"Front. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/j.arcmed.2011.11.004","article-title":"Early Cataract Formation Due to Galactokinase Deficiency: Impact of Newborn Screening","volume":"42","author":"Janzen","year":"2011","journal-title":"Arch. Med. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"25668","DOI":"10.1074\/jbc.M702076200","article-title":"Multiple and Additive Functions of ALDH3A1 and ALDH1A1: Cataract phenotype and ocular oxidative damage in Aldh3a1(-\/-)\/Aldh1a1(-\/-) knock-out mice","volume":"282","author":"Lassen","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"169","DOI":"10.20344\/amp.8223","article-title":"Paediatric Cataracts: A Retrospective Study of 12 Years (2004\u20132016)","volume":"30","author":"Moreira","year":"2017","journal-title":"Acta Med. Port."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e5","DOI":"10.1016\/j.pediatrneurol.2016.11.001","article-title":"Congenital Cataracts, Facial Dysmorphism, and Neuropathy Syndrome: Additional Clinical Features","volume":"67","author":"Makrygianni","year":"2017","journal-title":"Pediatr. Neurol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1038\/s41433-018-0277-y","article-title":"Unique presentation of congenital cataract concurrent with microcornea, microphthalmia plus posterior capsule defect in monozygotic twins caused by a novel GJA8 mutation","volume":"33","author":"Zhang","year":"2019","journal-title":"Eye"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.jaapos.2005.10.002","article-title":"Is there a latent period for the treatment of children with dense bilateral congenital cataracts?","volume":"10","author":"Lambert","year":"2006","journal-title":"J. AAPOS"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1007\/s00431-012-1700-1","article-title":"Congenital and infantile cataract: Aetiology and management","volume":"171","author":"Chan","year":"2012","journal-title":"Eur. J. Paediatr."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.jaapos.2005.07.008","article-title":"Visual acuity development after the implantation of unilateral in-traocular lenses in infants and young children","volume":"9","author":"Birch","year":"2005","journal-title":"J. AAPOS"},{"key":"ref_55","first-page":"72","article-title":"Visual Results after Primary Intraocular Lens Implantation or Contact Lens Correction for Aphakia in the First Year of Age","volume":"219","author":"Autrata","year":"2005","journal-title":"Int. J. Ophthalmol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1136\/bjophthalmol-2014-306394","article-title":"Risks and outcomes associated with primary intraocular lens implantation in children under 2 years of age: The IoLunder2 cohort study","volume":"99","author":"Solebo","year":"2015","journal-title":"Br. J. Ophthalmol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Infant Aphakia Treatment Study Group, Lambert, S.R., Buckley, E.G., Drews-Botsch, C., DuBois, L., Hartmann, E., Lynn, M.J., Plager, D.A., and Wilson, M.E. (2010). The Infant Aphakia Treatment Study: Design and clinical measures at enrollment: Design and clinical measures at enrollment. Arch. Ophthalmol., 128, 21\u201327.","DOI":"10.1001\/archophthalmol.2009.350"},{"key":"ref_58","unstructured":"Gillespie, R.L., and Black, G.C.M. (2016). Congenital Cataract, Springer International Publishing."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1002\/humu.24240","article-title":"Genome sequencing in congenital cataracts improves diagnostic yield","volume":"42","author":"Ma","year":"2021","journal-title":"Hum. Mutat."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1007\/s00417-011-1781-y","article-title":"A new locus in chromosome 2q37-qter is associated with posterior polar cataract","volume":"250","author":"Ouyang","year":"2012","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_61","unstructured":"(2023, March 25). VCV001174689.6\u2014ClinVar\u2014NCBI, Available online: https:\/\/www.ncbi.nlm.nih.gov\/clinvar\/variation\/1174689\/?new_evidence=true."},{"key":"ref_62","unstructured":"gnomAD (2023, March 25). SNV: 14-24679928-G-A(GRCh37). Available online: https:\/\/gnomad.broadinstitute.org\/variant\/14-24679928-G-A?dataset=gnomad_r2_1."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"108485","DOI":"10.1016\/j.exer.2021.108485","article-title":"AQP5 regulates vimentin expression via miR-124\u20133p.1 to protect lens transparency","volume":"205","author":"Tang","year":"2021","journal-title":"Exp. Eye Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1016\/j.gim.2022.03.005","article-title":"Cost-effectiveness of exome and genome sequencing for children with rare and undiagnosed conditions","volume":"24","author":"Lavelle","year":"2022","journal-title":"Genet. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.freeradbiomed.2016.06.031","article-title":"Mitochondrial Lon protease in human disease and aging: Including an etiologic classification of Lon-related diseases and disorders","volume":"100","author":"Bota","year":"2016","journal-title":"Free Radic. Biol. Med."},{"key":"ref_66","unstructured":"(2023, March 28). GeneCards Human Gene Database. LONP1 Gene\u2014GeneCards. Available online: https:\/\/www.genecards.org\/cgi-bin\/carddisp.pl?gene=LONP1&keywords=LONP1."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s00439-016-1747-6","article-title":"Novel phenotypes and loci identified through clinical genomics approaches to pediatric cataract","volume":"136","author":"Patel","year":"2017","journal-title":"Hum. Genet."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.jaapos.2017.10.012","article-title":"Clinical features of LONP1 -related infantile cataract","volume":"22","author":"Khan","year":"2018","journal-title":"J. AAPOS"},{"key":"ref_69","unstructured":"(2023, March 28). Available online: http:\/\/www.pantherdb.org\/tools\/csnpScore.do."},{"key":"ref_70","unstructured":"(2023, March 28). Grid Gateway Error. Available online: http:\/\/genetics.bwh.harvard.edu\/ggi\/cgi-bin\/ggi2.cgi."},{"key":"ref_71","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_72","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1038\/ejhg.2014.21","article-title":"The myosin chaperone UNC45B is involved in lens development and autosomal dominant juvenile cataract","volume":"22","author":"Hansen","year":"2014","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1038\/bjc.2017.374","article-title":"Targeting de novo lipogenesis as a novel approach in anti-cancer therapy","volume":"118","author":"Stoiber","year":"2018","journal-title":"Br. J. Cancer"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"836058","DOI":"10.3389\/fonc.2022.836058","article-title":"Acetyl-CoA Carboxylases and Diseases","volume":"12","author":"Wang","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"5828","DOI":"10.1167\/iovs.09-4015","article-title":"Human and Monkey Lenses Cultured with Calcium Ionophore Form \u03b1B-Crystallin Lacking the C-Terminal Lysine, a Prominent Feature of Some Human Cataracts","volume":"50","author":"Nakajima","year":"2009","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.jaapos.2022.03.013","article-title":"Unilateral cataract and congenital stationary night blindness in a child with novel variants in TRPM1","volume":"26","author":"Saleh","year":"2022","journal-title":"J. AAPOS"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1136\/bjo.86.7.782","article-title":"Aetiology of congenital and paediatric cataract in an Australian population","volume":"86","author":"Wirth","year":"2002","journal-title":"Br. J. Ophthalmol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1111\/j.1463-5224.2011.00903.x","article-title":"Congenital stationary night blindness is associated with the leopard complex in the miniature horse: Miniature horse congenital stationary night blindness is associated with the leopard complex","volume":"15","author":"Sandmeyer","year":"2012","journal-title":"Vet. Ophthalmol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e21288","DOI":"10.1096\/fj.202002037R","article-title":"Mutation of the TRPM3 cation channel underlies progressive cataract development and lens calcification associated with pro-fibrotic and immune cell responses","volume":"35","author":"Zhou","year":"2021","journal-title":"FASEB J."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/s41436-019-0686-8","article-title":"Technical standards for the interpretation and reporting of constitutional copy-number variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen)","volume":"22","author":"Riggs","year":"2020","journal-title":"Genet. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"818649","DOI":"10.3389\/fphys.2021.818649","article-title":"Physiological Mechanisms Regulating Lens Transport","volume":"12","author":"Giannone","year":"2021","journal-title":"Front. Physiol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.bbrc.2015.04.138","article-title":"Role of Aquaporin 0 in lens biomechanics","volume":"462","author":"Kumari","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"3960","DOI":"10.1167\/iovs.06-0229","article-title":"Accelerated Cataract Formation and Reduced Lens Epithelial Water Permeability in Aquaporin-1-Deficient Mice","volume":"47","author":"Verkman","year":"2006","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.exer.2018.02.001","article-title":"The klotho-related protein KLPH (lctl) has preferred expression in lens and is essential for expression of clic5 and normal lens suture formation","volume":"169","author":"Fan","year":"2018","journal-title":"Exp. Eye Res."},{"key":"ref_85","unstructured":"(2023, April 09). SIFT\u2014Predict Effects of Nonsynonmous\/Missense Variants. Available online: https:\/\/sift.bii.a-star.edu.sg\/."},{"key":"ref_86","unstructured":"(2023, April 09). Use\u2014Align GVGD. Available online: http:\/\/agvgd.hci.utah.edu\/agvgd_input.php."},{"key":"ref_87","unstructured":"(2023, April 09). GeneCards Human Gene Database. HSPE1 Gene\u2014GeneCards. Available online: https:\/\/www.genecards.org\/cgi-bin\/carddisp.pl?gene=HSPE1&keywords=hspe1."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1379\/1466-1268(2003)8<53:THGECS>2.0.CO;2","article-title":"The human genome encodes 10 \u03b1-crystallin\u2013related small heat shock proteins: HspB1\u201310","volume":"8","author":"Franck","year":"2003","journal-title":"Cell Stress Chaperones"},{"key":"ref_89","first-page":"19","article-title":"Small heat shock proteins\u2014Role in apoptosis, cancerogenesis and diseases associated with protein aggregation","volume":"53","author":"Laskowska","year":"2007","journal-title":"Postep. Biochem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"5107","DOI":"10.1007\/s11033-022-07222-6","article-title":"The protective role of HSP27 in ocular diseases","volume":"49","author":"Sooraj","year":"2022","journal-title":"Mol. Biol. Rep."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Fern\u00e1ndez-Alcalde, C., Nieves-Moreno, M., Noval, S., Peralta, J.M., Monta\u00f1o, V.E.F., del Pozo, \u00c1., Santos-Simarro, F., and Vallesp\u00edn, E. (2021). Molecular and Genetic Mechanism of Non-Syndromic Congenital Cataracts. Mutation Screening in Spanish Families. Genes, 12.","DOI":"10.3390\/genes12040580"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"102086","DOI":"10.1016\/j.ceb.2022.102086","article-title":"Roles of PIKfyve in multiple cellular pathways","volume":"76","author":"Weisman","year":"2022","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"26141","DOI":"10.1074\/jbc.M101722200","article-title":"Mammalian Cell Morphology and Endocytic Membrane Homeostasis Require Enzymatically Active Phosphoinositide 5-Kinase PIKfyve","volume":"276","author":"Ikonomov","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1126\/science.aaw9544","article-title":"Lipid-gated monovalent ion fluxes regulate endocytic traffic and support immune surveillance","volume":"367","author":"Freeman","year":"2020","journal-title":"Science"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"e71256","DOI":"10.7554\/eLife.71256","article-title":"Disruption of PIKFYVE causes congenital cataract in human and zebrafish","volume":"11","author":"Mei","year":"2022","journal-title":"eLife"},{"key":"ref_96","unstructured":"(2023, April 12). GeneCards Human Gene Database. CHMP4A Gene\u2014GeneCards. Available online: https:\/\/www.genecards.org\/cgi-bin\/carddisp.pl?gene=CHMP4A&keywords=chmp4a."},{"key":"ref_97","unstructured":"(2023, February 02). GeneCards Human Gene Database. GeneCards\u2014Human Genes. Available online: https:\/\/www.genecards.org\/."},{"key":"ref_98","unstructured":"(2023, April 12). Cataract 32, Multiple Types Disease: Malacards\u2014Research Articles, Drugs, Genes, Clinical Trials. Available online: https:\/\/www.malacards.org\/card\/cataract_32_multiple_types."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.diff.2019.07.003","article-title":"A charged multivesicular body protein (CHMP4B) is required for lens growth and differentiation","volume":"109","author":"Zhou","year":"2019","journal-title":"Differentiation"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1086\/519980","article-title":"CHMP4B, a Novel Gene for Autosomal Dominant Cataracts Linked to Chromosome 20q","volume":"81","author":"Shiels","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Kem\u00e9ny, K.K., and Ducza, E. (2022). Physiological Cooperation between Aquaporin 5 and TRPV4. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231911634"},{"key":"ref_102","first-page":"2448","article-title":"The membrane proteome of the mouse lens fiber cell","volume":"15","author":"Bassnett","year":"2009","journal-title":"Mol. Vis."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.exer.2012.12.004","article-title":"Verification and spatial localization of aquaporin-5 in the ocular lens","volume":"108","author":"Grey","year":"2013","journal-title":"Exp. Eye Res."},{"key":"ref_104","unstructured":"NCBI (2022, May 24). Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/."},{"key":"ref_105","unstructured":"(2023, February 02). DECIPHER v11.12: Mapping the Clinical Genome. Available online: https:\/\/www.deciphergenomics.org\/."},{"key":"ref_106","unstructured":"gnomAD (2023, February 03). Available online: https:\/\/gnomad.broadinstitute.org\/."},{"key":"ref_107","unstructured":"(2023, February 03). UCSC Genome Browser Home. Available online: https:\/\/genome.ucsc.edu\/."},{"key":"ref_108","unstructured":"(2023, February 03). Cat-Map. Available online: https:\/\/cat-map.wustl.edu\/."},{"key":"ref_109","unstructured":"(2023, March 24). VarSome the Human Genomics Community. Available online: https:\/\/varsome.com\/."},{"key":"ref_110","unstructured":"(2023, February 03). Franklin. Available online: https:\/\/franklin.genoox.com\/clinical-db\/hom."},{"key":"ref_111","unstructured":"(2023, March 24). GeneMatcher. Available online: https:\/\/genematcher.org\/."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/14\/11429\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:11:36Z","timestamp":1760127096000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/14\/11429"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,13]]},"references-count":111,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["ijms241411429"],"URL":"https:\/\/doi.org\/10.3390\/ijms241411429","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,13]]}}}