eCite Digital Repository

Mutations of the EPHA2 receptor tyrosine kinase gene cause autosomal dominant congenital cataract


Zhang, T and Hua, R and Xiao, W and Burdon, KP and Bhattacharya, SS and Craig, JE and Shang, D and Zhao, X and Mackey, DA and Moore, AT and Luo, Y and Zhang, J and Zhang, X, Mutations of the EPHA2 receptor tyrosine kinase gene cause autosomal dominant congenital cataract, Human Mutation, 30, (5) pp. E603-E611. ISSN 1059-7794 (2009) [Refereed Article]

Copyright Statement

Copyright 2009 WILEY-LISS, INC.

DOI: doi:10.1002/humu.20995


Congenital cataracts (CCs) are clinically and genetically heterogeneous. Mutations in the same gene may lead to CCs differing in inheritance, morphology and severity. Loci for autosomal dominant posterior polar CC and total CC have both been mapped to the chromosomal 1p36 region harboring the EPHA2 receptor tyrosine kinase gene. Here, we report mutations of EPHA2 in three CC families from different ancestral groups. In a Chinese family with posterior polar CC, we identified a missense mutation, c.2819C>T (p.T940I), replacing a critical amino acid that functions at the receptor oligomerization interface. In a British family with posterior polar CC and an Australian family with total CC, we found a frameshift mutation (c.2915-2916delTG) and a splicing mutation (c.2826-9G>A), respectively. These two mutations are predicted to produce novel C-terminal polypeptides with 39 identical amino acids. Yeast two-hybrid analysis showed stronger interaction between the total CC-associated mutant EPHA2 and low molecular weight protein-tyrosine phosphatase, a negative regulator of EPHA2 signaling. Our results implicate the Eph-ephrin signaling system in development of human cataract and provide a novel insight into the molecular mechanism underlying the pathogenesis of human CCs.

Item Details

Item Type:Refereed Article
Keywords:Congenital cataract; Eph receptor tyrosine kinase; EPHA2; Frameshift; Missense; Splicing
Research Division:Biomedical and Clinical Sciences
Research Group:Ophthalmology and optometry
Research Field:Ophthalmology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Burdon, KP (Professor Kathryn Burdon)
ID Code:91087
Year Published:2009
Web of Science® Times Cited:82
Deposited By:Menzies Institute for Medical Research
Deposited On:2014-05-07
Last Modified:2014-12-15

Repository Staff Only: item control page