Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2006 Jan;43(1):e2.
doi: 10.1136/jmg.2005.034108.

A novel GJA8 mutation is associated with autosomal dominant lamellar pulverulent cataract: further evidence for gap junction dysfunction in human cataract

A Arora, P J Minogue, X Liu, M A Reddy, J R Ainsworth, S S Bhattacharya, A R Webster, D M Hunt, L Ebihara, A T Moore, E C Beyer, V M Berthoud

A novel GJA8 mutation is associated with autosomal dominant lamellar pulverulent cataract: further evidence for gap junction dysfunction in human cataract

A Arora et al. J Med Genet. 2006 Jan.

Abstract

Purpose: To identify the gene responsible for autosomal dominant lamellar pulverulent cataract in a four-generation British family and characterise the functional and cellular consequences of the mutation.

Methods: Linkage analysis was used to identify the disease locus. The GJA8 gene was sequenced directly. Functional behaviour and cellular trafficking of connexins were examined by expression in Xenopus oocytes and HeLa cells.

Results: A 262C>A transition that resulted in the replacement of proline by glutamine (P88Q) in the coding region of connexin50 (Cx50) was identified. hCx50P88Q did not induce intercellular conductance and significantly inhibited gap junctional activity of co-expressed wild type hCx50 RNA in paired Xenopus oocytes. In transfected cells, immunoreactive hCx50P88Q was confined to the cytoplasm but showed a temperature sensitive localisation at gap junctional plaques.

Conclusions: The pulverulent cataract described in this family is associated with a novel GJA8 mutation and has a different clinical phenotype from previously described GJA8 mutants. The cataract likely results from lack of gap junction function. The lack of function was associated with improper targeting to the plasma membrane, most probably due to protein misfolding.

PubMed Disclaimer

Conflict of interest statement

Competing interests: none declared

References

    1. Resnikoff S, Pascolini D, Etya'ale D, Kocur I, Pararajasegaram R, Pokharel G P, Mariotti S P. Global data on visual impairment in the year 2002. Bull World Health Organ 200482844–851. - PMC - PubMed
    1. Gilbert C E, Canovas R, Hagan M, Rao S, Foster A. Causes of childhood blindness: results from West Africa, South India and Chile. Eye 19937184–188. - PubMed
    1. Reddy M A, Francis P J, Berry V, Bhattacharya S S, Moore A T. Molecular genetic basis of inherited cataract and associated phenotypes. Surv Ophthalmol 200449300–315. - PubMed
    1. Mackay D, Ionides A, Kibar Z, Rouleau G, Berry V, Moore A, Shiels A, Bhattacharya S. Connexin46 mutations in autosomal dominant congenital cataract. Am J Hum Genet 1999641357–1364. - PMC - PubMed
    1. Rees M I, Watts P, Fenton I, Clarke A, Snell R G, Owen M J, Gray J. Further evidence of autosomal dominant congenital zonular pulverulent cataracts linked to 13q11 (CZP3) and a novel mutation in connexin 46 (GJA3). Hum Genet 2000106206–209. - PubMed

Publication types