{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T09:54:25Z","timestamp":1768902865426,"version":"3.49.0"},"reference-count":20,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T00:00:00Z","timestamp":1632960000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["R01DC016295"],"award-info":[{"award-number":["R01DC016295"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hereditary congenital cataract (HCC) is clinically and genetically heterogeneous. We investigated HCC that segregates in three inbred families (LUCC03, LUCC16, and LUCC24). Ophthalmological examinations revealed cataracts with variability related to the age of onset segregating in a recessive manner in these families. Exome sequencing of probands identified a novel homozygous c.2710delG;p.(Val904Cysfs*36) EPHA2 variant in LUCC03 and a known homozygous c.2353G&gt;A;p.(Ala785Thr) EPHA2 variant in the other two recessive families. EPHA2 encodes a transmembrane tyrosine kinase receptor, which is primarily involved in membrane-transport, cell-cell adhesion, and repulsion signaling processes. Computational structural modeling predicts that substitution of a threonine for an alanine p.(Ala785Thr) results in the formation of three new hydrogen bonds with the neighboring residues, which causes misfolding of EPHA2 in both scenarios. Insights from our study will facilitate counseling regarding the molecular and phenotypic landscape of EPHA2-related HCC.<\/jats:p>","DOI":"10.3390\/ijms221910655","type":"journal-article","created":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T10:55:40Z","timestamp":1633085740000},"page":"10655","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Biallelic Variants in EPHA2 Identified in Three Large Inbred Families with Early-Onset Cataract"],"prefix":"10.3390","volume":"22","author":[{"given":"Priya","family":"Jarwar","sequence":"first","affiliation":[{"name":"Institute of Biotechnology and Genetic Engineering, The University of Sindh, Jamshoro 76090, Pakistan"},{"name":"Department of Molecular Biology & Genetics, Liaquat University of Medical and Health Sciences, Jamshoro 76090, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shakeel Ahmed","family":"Sheikh","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology & Genetics, Liaquat University of Medical and Health Sciences, Jamshoro 76090, Pakistan"},{"name":"Department of Otorhinolaryngology Head and Neck Surgery, School of Medicine, University of Maryland, Baltimore, MD 21201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yar Muhammad","family":"Waryah","sequence":"additional","affiliation":[{"name":"Scientific Ophthalmic and Research Laboratory, Sindh Institute of Ophthalmology and Visual Sciences, Hyderabad 71500, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ikram Uddin","family":"Ujjan","sequence":"additional","affiliation":[{"name":"Department of Pathology, Liaquat University of Medical and Health Sciences, Jamshoro 76090, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saima","family":"Riazuddin","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology & Genetics, Liaquat University of Medical and Health Sciences, Jamshoro 76090, Pakistan"},{"name":"Department of Molecular Biology and Biochemistry, School of Medicine, University of Maryland, Baltimore, MD 21201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2596-9032","authenticated-orcid":false,"given":"Ali Muhammad","family":"Waryah","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology & Genetics, Liaquat University of Medical and Health Sciences, Jamshoro 76090, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2914-4502","authenticated-orcid":false,"given":"Zubair M.","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery, School of Medicine, University of Maryland, Baltimore, MD 21201, USA"},{"name":"Department of Molecular Biology and Biochemistry, School of Medicine, University of Maryland, Baltimore, MD 21201, USA"},{"name":"Department of Ophthalmology and Visual Sciences, School of Medicine, University of Maryland, Baltimore, MD 21201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1038\/eye.2016.156","article-title":"Global prevalence of childhood cataract: A systematic review","volume":"30","author":"Sheeladevi","year":"2016","journal-title":"Eye"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Irum, B., Khan, S.Y., Ali, M., Kaul, H., Kabir, F., Rauf, B., Fatima, F., Nadeem, R., Khan, A.O., and Obaisi, S.A. 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