How to cite this article: Richter L, Flodman P, Barria von-Bischhoffshausen F, Burch D, Brown S, Nguyen L, Turner J, Spence MA, Bateman JB. 2008. Clinical variability of autosomal dominant cataract, microcornea and corneal opacity and novel mutation in the alpha A crystallin gene (CRYAA). Am J Med Genet Part A 146A:833–842.
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Research Article
Clinical variability of autosomal dominant cataract, microcornea and corneal opacity and novel mutation in the alpha A crystallin gene (CRYAA)†
Article first published online: 26 FEB 2008
DOI: 10.1002/ajmg.a.32236
Copyright © 2008 Wiley-Liss, Inc.
Additional Information
How to Cite
Richter, L., Flodman, P., Barria von-Bischhoffshausen, F., Burch, D., Brown, S., Nguyen, L., Turner, J., Spence, M. A. and Bateman, J. B. (2008), Clinical variability of autosomal dominant cataract, microcornea and corneal opacity and novel mutation in the alpha A crystallin gene (CRYAA). American Journal of Medical Genetics Part A, 146A: 833–842. doi: 10.1002/ajmg.a.32236
- †
Publication History
- Issue published online: 24 MAR 2008
- Article first published online: 26 FEB 2008
- Manuscript Accepted: 8 OCT 2007
- Manuscript Received: 21 DEC 2006
Funded by
- National Eye Institute. Grant Number: EY08282
Keywords:
- cataract;
- intrafamilial variability;
- CRYAA mutation;
- autosomal dominant;
- alpha crystalline A;
- corneal opacity;
- microcornea
Abstract
We studied 28 individuals from a four-generation Chilean family (ADC54) including 13 affected individuals with cataracts, microcornea and/or corneal opacity. All individuals underwent a complete ophthalmologic exam. We screened with a panel of polymorphic DNA markers for known loci that cause autosomal dominant cataracts, if mutated, and refined the locus using the ABI Prism Linkage Mapping Set Version 2.5, and calculated two-point lod scores. Novel PCR primers were designed for the three coding exons, including intron–exon borders, of the candidate gene alpha A crystallin (CRYAA). Clinically, affected individuals had diverse and novel cataracts with variable morphology (anterior polar, cortical, embryonal, fan-shaped, anterior subcapsular). Microcornea and corneal opacity was evident in some. Marker D21S171 gave a lod score of 4.89 (θm = θf = 0). CRYAA had a G414A transition that segregated with the disease and resulted in an amino acid alteration (R116H). The phenotypic variability within this family was significant with novel features of the cataracts and a corneal opacity. With the exception of iris coloboma, the clinical features in all six previously reported families with mutations in the CRYAA gene were found in this family. We identified a novel G414A transition in exon 3 of CRYAA that co-segregated with an autosomal dominant phenotype. The resulting amino acid change R116H is in a highly conserved region and represents a change in charge. The genotype–phenotype correlation of this previously unreported mutation provides evidence that other factors, genetic and/or environmental, may influence the development of cataract as a result of this alteration. © 2008 Wiley-Liss, Inc.