Cargando…
Biallelic Variants in EPHA2 Identified in Three Large Inbred Families with Early-Onset Cataract
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...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8508826/ https://www.ncbi.nlm.nih.gov/pubmed/34638995 http://dx.doi.org/10.3390/ijms221910655 |
_version_ | 1784582189594181632 |
---|---|
author | Jarwar, Priya Sheikh, Shakeel Ahmed Waryah, Yar Muhammad Ujjan, Ikram Uddin Riazuddin, Saima Waryah, Ali Muhammad Ahmed, Zubair M. |
author_facet | Jarwar, Priya Sheikh, Shakeel Ahmed Waryah, Yar Muhammad Ujjan, Ikram Uddin Riazuddin, Saima Waryah, Ali Muhammad Ahmed, Zubair M. |
author_sort | Jarwar, Priya |
collection | PubMed |
description | 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>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. |
format | Online Article Text |
id | pubmed-8508826 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-85088262021-10-13 Biallelic Variants in EPHA2 Identified in Three Large Inbred Families with Early-Onset Cataract Jarwar, Priya Sheikh, Shakeel Ahmed Waryah, Yar Muhammad Ujjan, Ikram Uddin Riazuddin, Saima Waryah, Ali Muhammad Ahmed, Zubair M. Int J Mol Sci Brief Report 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>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. MDPI 2021-09-30 /pmc/articles/PMC8508826/ /pubmed/34638995 http://dx.doi.org/10.3390/ijms221910655 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Brief Report Jarwar, Priya Sheikh, Shakeel Ahmed Waryah, Yar Muhammad Ujjan, Ikram Uddin Riazuddin, Saima Waryah, Ali Muhammad Ahmed, Zubair M. Biallelic Variants in EPHA2 Identified in Three Large Inbred Families with Early-Onset Cataract |
title | Biallelic Variants in EPHA2 Identified in Three Large Inbred Families with Early-Onset Cataract |
title_full | Biallelic Variants in EPHA2 Identified in Three Large Inbred Families with Early-Onset Cataract |
title_fullStr | Biallelic Variants in EPHA2 Identified in Three Large Inbred Families with Early-Onset Cataract |
title_full_unstemmed | Biallelic Variants in EPHA2 Identified in Three Large Inbred Families with Early-Onset Cataract |
title_short | Biallelic Variants in EPHA2 Identified in Three Large Inbred Families with Early-Onset Cataract |
title_sort | biallelic variants in epha2 identified in three large inbred families with early-onset cataract |
topic | Brief Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8508826/ https://www.ncbi.nlm.nih.gov/pubmed/34638995 http://dx.doi.org/10.3390/ijms221910655 |
work_keys_str_mv | AT jarwarpriya biallelicvariantsinepha2identifiedinthreelargeinbredfamilieswithearlyonsetcataract AT sheikhshakeelahmed biallelicvariantsinepha2identifiedinthreelargeinbredfamilieswithearlyonsetcataract AT waryahyarmuhammad biallelicvariantsinepha2identifiedinthreelargeinbredfamilieswithearlyonsetcataract AT ujjanikramuddin biallelicvariantsinepha2identifiedinthreelargeinbredfamilieswithearlyonsetcataract AT riazuddinsaima biallelicvariantsinepha2identifiedinthreelargeinbredfamilieswithearlyonsetcataract AT waryahalimuhammad biallelicvariantsinepha2identifiedinthreelargeinbredfamilieswithearlyonsetcataract AT ahmedzubairm biallelicvariantsinepha2identifiedinthreelargeinbredfamilieswithearlyonsetcataract |