A novel mutation in the Connexin 46 gene causes autosomal dominant congenital cataract with incomplete penetrance

Burdon, Kathryn P.; Wirth, Manuel; Mackey, David A.; Russell‐Eggitt, Isabelle; Craig, Jamie E; Elder, James E; Dickinson, Joanne L.; Sale, Michèle M.

doi:10.1136/jmg.2004.018333

Cited by 45 publications

(22 citation statements)

References 25 publications

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“…24 25 Furthermore, mutations in the genes encoding Cx46 and Cx50 have been reported in autosomal dominant congenital cataract in man. [4][5][6][7][8][9][10][11][12][13][14] Each of these mutations is associated with a nuclear pulverulent phenotype. In contrast, hCx50P88Q results in a lamellar pulverulent cataract; the opacity appears confined to the fetal nucleus with the embryonic nucleus remaining clear.…”

Section: Discussionmentioning

confidence: 99%

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

Arora

2005

Journal of Medical Genetics

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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.

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Section: Discussionmentioning

confidence: 99%

“…3 Several mutations in connexin46 and connexin50 (Cx50) have been identified in autosomal dominant isolated congenital cataract. [4][5][6][7][8][9][10][11][12][13][14] Here, we report a novel GJA8 mutation, hCx50P88Q, in a family with lamellar pulverulent cataract and describe the consequences of the mutation.…”

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confidence: 99%

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

Arora

2005

Journal of Medical Genetics

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“…Among these juvenile cataracts are cases associated with defined amino acid substitutions in g-crystallins [54], a-crystallin [55], b-crystallins [56], aquaporin-0 [57], and connexins [58]. Table 1 summarizes known human inherited cataracts caused by mutations in crystallin genes [9,[54][55][56][59][60][61][62][63][64][65][66][67][68][69][70][71][72][73].…”

Section: Juvenile Cataracts Associated With Autosomal Dominant Mutationsmentioning

confidence: 99%

Cataract as a Protein‐Aggregation Disease

Wang

King

2010

Protein Misfolding Diseases

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“…Initial mapping by Mackay et al [81] showed a locus linkage of CZP3 to chromosome 13 and led to the identification of missense mutations in Cx46 [18,109].…”

Section: Cx46 and Cx50 In Ocular Diseasementioning

confidence: 98%

Gap junctions in inherited human disease

Zoidl

Dermietzel

2010

Pflugers Arch - Eur J Physiol

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Gap junctions (GJ) provide direct intercellular communication. The structures underlying these cell junctions are membrane-associated channels composed of six integral membrane connexin (Cx) proteins, which can form communicating channels connecting the cytoplasms of adjacent cells. This provides coupled cells with a direct pathway for sharing ions, nutrients, or small metabolites to establish electrical coupling or balancing metabolites in various tissues. Genetic approaches have uncovered a still growing number of mutations in Cxs related to human diseases including deafness, skin disease, peripheral and central neuropathies, cataracts, or cardiovascular dysfunctions. The discovery of a growing number of inherited human disorders provides an unequivocal demonstration that gap junctional communication is crucial for diverse physiological processes.

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A novel mutation in the Connexin 46 gene causes autosomal dominant congenital cataract with incomplete penetrance

Cited by 45 publications

References 25 publications

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

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

Cataract as a Protein‐Aggregation Disease

Gap junctions in inherited human disease

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