Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Med Genet
2008 Mar 01;453:155-60. doi: 10.1136/jmg.2007.051029.
Show Gene links
Show Anatomy links
A novel connexin50 mutation associated with congenital nuclear pulverulent cataracts.
Arora A
,
Minogue PJ
,
Liu X
,
Addison PK
,
Russel-Eggitt I
,
Webster AR
,
Hunt DM
,
Ebihara L
,
Beyer EC
,
Berthoud VM
,
Moore AT
.
???displayArticle.abstract???
To screen for mutations of connexin50 (Cx50)/GJA8 in a panel of patients with inherited cataract and to determine the cellular and functional consequences of the identified mutation. All patients in the study underwent a full clinical examination and leucocyte DNA was extracted from venous blood. The GJA8 gene was sequenced directly. Connexin function and cellular trafficking were examined by expression in Xenopus oocytes and HeLa cells. Screening of the GJA8 gene identified a 139 G to A transition that resulted in the replacement of aspartic acid by asparagine (D47N) in the coding region of Cx50. This change co-segregated with cataract among affected members of a family with autosomal dominant nuclear pulverulent cataracts. While pairs of Xenopus oocytes injected with wild type Cx50 RNA formed functional gap junction channels, pairs of oocytes injected with Cx50D47N showed no detectable intercellular conductance. Co-expression of Cx50D47N did not inhibit gap junctional conductance of wild type Cx50. In transiently transfected HeLa cells, wild type Cx50 localised to appositional membranes and within the perinuclear region, but Cx50D47N showed no immunostaining at appositional membranes with immunoreactivity confined to the cytoplasm. Incubation of HeLa cells transfected with Cx50D47N at 27 degrees C resulted in formation of gap junctional plaques. The pulverulent cataracts present in members of this family are associated with a novel GJA8 mutation, Cx50D47N, that acts as a loss-of-function mutation. The consequent decrease in lens intercellular communication and changes associated with intracellular retention of the mutant connexin may contribute to cataract formation.
???displayArticle.pubmedLink???
18006672
???displayArticle.pmcLink???PMC2756454 ???displayArticle.link???J Med Genet ???displayArticle.grants???[+]
Addison,
A novel mutation in the connexin 46 gene (GJA3) causes autosomal dominant zonular pulverulent cataract in a Hispanic family.
2006, Pubmed
Addison,
A novel mutation in the connexin 46 gene (GJA3) causes autosomal dominant zonular pulverulent cataract in a Hispanic family.
2006,
Pubmed
Arora,
A novel GJA8 mutation is associated with autosomal dominant lamellar pulverulent cataract: further evidence for gap junction dysfunction in human cataract.
2006,
Pubmed
,
Xenbase
Baldo,
Gap junctional coupling in lenses from alpha(8) connexin knockout mice.
2001,
Pubmed
Bennett,
A novel missense mutation in the gene for gap-junction protein alpha3 (GJA3) associated with autosomal dominant "nuclear punctate" cataracts linked to chromosome 13q.
2004,
Pubmed
Berry,
Connexin 50 mutation in a family with congenital "zonular nuclear" pulverulent cataract of Pakistani origin.
1999,
Pubmed
Berthoud,
Loss of function and impaired degradation of a cataract-associated mutant connexin50.
2003,
Pubmed
Beyer,
Antisera directed against connexin43 peptides react with a 43-kD protein localized to gap junctions in myocardium and other tissues.
1989,
Pubmed
Burdon,
A novel mutation in the Connexin 46 gene causes autosomal dominant congenital cataract with incomplete penetrance.
2004,
Pubmed
Denning,
Processing of mutant cystic fibrosis transmembrane conductance regulator is temperature-sensitive.
1992,
Pubmed
,
Xenbase
Devi,
Novel mutations in GJA8 associated with autosomal dominant congenital cataract and microcornea.
2006,
Pubmed
Devi,
Novel mutations in GJA3 associated with autosomal dominant congenital cataract in the Indian population.
2005,
Pubmed
Ebihara,
Distinct behavior of connexin56 and connexin46 gap junctional channels can be predicted from the behavior of their hemi-gap-junctional channels.
1995,
Pubmed
,
Xenbase
Ebihara,
Expression of gap junctional proteins in Xenopus oocyte pairs.
1992,
Pubmed
,
Xenbase
Favor,
A comparison of the dominant cataract and recessive specific-locus mutation rates induced by treatment of male mice with ethylnitrosourea.
1983,
Pubmed
Gerido,
Genetic background influences cataractogenesis, but not lens growth deficiency, in Cx50-knockout mice.
2003,
Pubmed
Gong,
Genetic factors influence cataract formation in alpha 3 connexin knockout mice.
1999,
Pubmed
Goodenough,
The crystalline lens. A system networked by gap junctional intercellular communication.
1992,
Pubmed
Hansen,
The congenital "ant-egg" cataract phenotype is caused by a missense mutation in connexin46.
2006,
Pubmed
Jiang,
A novel mutation in GJA3 (connexin46) for autosomal dominant congenital nuclear pulverulent cataract.
2003,
Pubmed
Li,
A novel connexin46 (GJA3) mutation in autosomal dominant congenital nuclear pulverulent cataract.
2004,
Pubmed
Mackay,
Connexin46 mutations in autosomal dominant congenital cataract.
1999,
Pubmed
Martin,
Properties of connexin26 gap junctional proteins derived from mutations associated with non-syndromal heriditary deafness.
1999,
Pubmed
Marziano,
Mutations in the gene for connexin 26 (GJB2) that cause hearing loss have a dominant negative effect on connexin 30.
2003,
Pubmed
Mathias,
Physiological properties of the normal lens.
1997,
Pubmed
Musil,
Expression of the gap junction protein connexin43 in embryonic chick lens: molecular cloning, ultrastructural localization, and post-translational phosphorylation.
1990,
Pubmed
Oguchi,
Clinical features of patients with GJB2 (connexin 26) mutations: severity of hearing loss is correlated with genotypes and protein expression patterns.
2005,
Pubmed
Pal,
Molecular mechanism underlying a Cx50-linked congenital cataract.
1999,
Pubmed
,
Xenbase
Paul,
Connexin46, a novel lens gap junction protein, induces voltage-gated currents in nonjunctional plasma membrane of Xenopus oocytes.
1991,
Pubmed
,
Xenbase
Polyakov,
Mutation in the connexin 50 gene (GJA8) in a Russian family with zonular pulverulent cataract.
2001,
Pubmed
Reddy,
Molecular genetic basis of inherited cataract and associated phenotypes.
2004,
Pubmed
Rees,
Further evidence of autosomal dominant congenital zonular pulverulent cataracts linked to 13q11 (CZP3) and a novel mutation in connexin 46 (GJA3).
2000,
Pubmed
Richard,
Missense mutations in GJB2 encoding connexin-26 cause the ectodermal dysplasia keratitis-ichthyosis-deafness syndrome.
2002,
Pubmed
Rong,
Disruption of Gja8 (alpha8 connexin) in mice leads to microphthalmia associated with retardation of lens growth and lens fiber maturation.
2002,
Pubmed
Saez,
Plasma membrane channels formed by connexins: their regulation and functions.
2003,
Pubmed
Sellitto,
Connexin50 is essential for normal postnatal lens cell proliferation.
2004,
Pubmed
Shiels,
A missense mutation in the human connexin50 gene (GJA8) underlies autosomal dominant "zonular pulverulent" cataract, on chromosome 1q.
1998,
Pubmed
Steele,
A mutation in the connexin 50 (Cx50) gene is a candidate for the No2 mouse cataract.
1998,
Pubmed
Tong,
Exchange of gating properties between rat cx46 and chicken cx45.6.
2004,
Pubmed
,
Xenbase
Vanita,
A novel mutation in GJA8 associated with autosomal dominant congenital cataract in a family of Indian origin.
2006,
Pubmed
van Steensel,
A novel connexin 26 mutation in a patient diagnosed with keratitis-ichthyosis-deafness syndrome.
2002,
Pubmed
White,
Mouse Cx50, a functional member of the connexin family of gap junction proteins, is the lens fiber protein MP70.
1992,
Pubmed
,
Xenbase
White,
Targeted ablation of connexin50 in mice results in microphthalmia and zonular pulverulent cataracts.
1998,
Pubmed
Willoughby,
A novel GJA8 mutation in an Iranian family with progressive autosomal dominant congenital nuclear cataract.
2003,
Pubmed
Xu,
Characterization of a mouse Cx50 mutation associated with the No2 mouse cataract.
1999,
Pubmed
,
Xenbase
Yoshimura,
Mutations of connexin32 in Charcot-Marie-Tooth disease type X interfere with cell-to-cell communication but not cell proliferation and myelin-specific gene expression.
1998,
Pubmed
Zheng,
[A heterozygous transversion of connexin 50 in a family with congenital nuclear cataract in the northeast of China].
2005,
Pubmed