Communicated by Andreas Gal
Identification of a Novel Oligomerization Disrupting Mutation in CRYΑA Associated with Congenital Cataract in a South Australian Family
Article first published online: 17 JAN 2013
© 2012 Wiley Periodicals, Inc.
Volume 34, Issue 3, pages 435–438, March 2013
How to Cite
Laurie, K. J., Dave, A., Straga, T., Souzeau, E., Chataway, T., Sykes, M. J., Casey, T., Teo, T., Pater, J., Craig, J. E., Sharma, S. and Burdon, K. P. (2013), Identification of a Novel Oligomerization Disrupting Mutation in CRYΑA Associated with Congenital Cataract in a South Australian Family. Hum. Mutat., 34: 435–438. doi: 10.1002/humu.22260
These authors contributed equally to this work.
Contract grant sponsors: National Health and Medical Research Council (NHMRC) of Australia (426753); Channel 7 Children's Research Foundation, South Australia.
- Issue published online: 18 FEB 2013
- Article first published online: 17 JAN 2013
- Accepted manuscript online: 15 DEC 2012 10:15PM EST
- Manuscript Accepted: 5 DEC 2012
- Manuscript Received: 17 JUN 2012
- National Health and Medical Research Council (NHMRC) of Australia. Grant Number: 426753
- Channel 7 Children's Research Foundation, South Australia
- ocular lens;
- protein analysis;
Congenital cataract is a heterogeneous disorder causing severe visual impairment in affected children. We screened four South Australian families with autosomal dominant congenital cataract for mutations in 10 crystallin genes known to cause congenital cataract. We identified a novel segregating heterozygous mutation, c.62G>A (p.R21Q), in the CRYΑA gene in one family. Western blotting of proteins freshly extracted from cataractous lens material of the proband demonstrated a marked reduction in the amount of the high-molecular-weight oligomers seen in the lens material of an unaffected individual. We conclude that the p.R21Q mutation, which is located in the highly conserved and structurally significant N-terminal region of the protein, is responsible for the cataract phenotype observed in the family as this mutation likely reduces the formation of the functional oligomeric alpha-crystallin.