Biallelic Variants in Identified in Three Large Inbred Families with Early-Onset Cataract
Sheikh, Shakeel Ahmed
Waryah, Yar Muhammad
Ujjan, Ikram Uddin
Waryah, Ali Muhammad
Ahmed, Zubair M
JournalInternational Journal of Molecular Sciences
MetadataShow full item record
AbstractHereditary 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>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.
hereditary congenital cataract
tyrosine kinase receptor
Identifier to cite or link to this itemhttp://hdl.handle.net/10713/16869
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