Institute of Biotechnology and Genetic Engineering, The University of Sindh, Jamshoro 76090, Pakistan.
Department of Molecular Biology & Genetics, Liaquat University of Medical and Health Sciences, Jamshoro 76090, Pakistan.
Int J Mol Sci. 2021 Sep 30;22(19):10655. doi: 10.3390/ijms221910655.
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) variant in LUCC03 and a known homozygous c.2353G>A;p.(Ala785Thr) variant in the other two recessive families. 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 -related HCC.
遗传性先天性白内障（HCC）在临床上和遗传上具有异质性。我们研究了在三个近交系家族（LUCC03、LUCC16 和 LUCC24）中分离的 HCC。眼科检查显示白内障具有与发病年龄相关的可变性，这些家族以隐性方式分离。先证者的外显子组测序在 LUCC03 中发现了一个新的纯合 c.2710delG;p.（Val904Cysfs*36）变异，在另外两个隐性家族中发现了已知的纯合 c.2353G>A;p.（Ala785Thr）变异。 编码一个跨膜酪氨酸激酶受体，主要参与膜转运、细胞-细胞黏附和排斥信号转导过程。计算结构建模预测，丙氨酸 p.（Ala785Thr）被苏氨酸取代会导致与邻近残基形成三个新的氢键，这两种情况下都会导致 EPHA2 的错误折叠。我们的研究结果将有助于咨询 - 相关 HCC 的分子和表型景观。
