GJA8 gene

Overview

Gene (OMIM No.)	GJA8 (#600897)
Function of gene/protein	Protein: gap junction alpha 3 protein/ connexin 50 Structural component of lens fibre gap junctions Formation of channels through which neighboring cells can communicate and allow small molecules and ions to diffuse between cells Maintaining lens transparency and its optical properties by regulating ionic and water balance in lens cells
Clinical phenotype (OMIM phenotype no.)	Cataract 1, multiple types (#116200)
Inheritance	Autosomal dominant
Ocular features	Congenital cataract (zonular pulverulent, nuclear progressive) Anterior segment dysgenesis (ASD) (usually microcornea – cataract-microcornea syndrome) Microphthalmia, anophthalmia, coloboma (MAC) spectrum Glaucoma
Systemic features	No extraocular features have been reported
Key investigations	Measurement of corneal diameter B-scan USS to measure axial length to document microphthalmia and detect any posterior segment abnormalities Electrophysiology TORCH screen Assessment with a pediatrician if suspicious of systemic involvement
Molecular diagnosis	Next generation sequencing Targeted gene panels (cataract) Whole exome sequencing Whole genome sequencing
Management	Ocular Management of congenital cataract Management of anterior segment dysgenesis Management of MAC
Therapies under research	None at present
Further information	OMIM

Arora A, Minogue PJ, Liu X, et al. A novel connexin50 mutation associated with congenital nuclear pulverulent cataracts. J Med Genet. 2008;45(3):155‐160
Berry V, Mackay D, Khaliq S, et al. Connexin 50 mutation in a family with congenital “zonular nuclear” pulverulent cataract of Pakistani origin. Hum Genet. 1999;105(1-2):168‐170
Gong X, Baldo GJ, Kumar NM, Gilula NB, Mathias RT. Gap junctional coupling in lenses lacking alpha3 connexin. Proc Natl Acad Sci U S A. 1998;95(26):15303‐15308
Gong X, Li E, Klier G, et al. Disruption of alpha3 connexin gene leads to proteolysis and cataractogenesis in mice. Cell. 1997;91(6):833‐843
Polyakov AV, Shagina IA, Khlebnikova OV, Evgrafov OV. Mutation in the connexin 50 gene (GJA8) in a Russian family with zonular pulverulent cataract. Clin Genet. 2001;60(6):476‐478
Shiels A, Mackay D, Ionides A, Berry V, Moore A, Bhattacharya S. A missense mutation in the human connexin50 gene (GJA8) underlies autosomal dominant “zonular pulverulent” cataract, on chromosome 1q. Am J Hum Genet. 1998;62(3):526‐532
White TW, Goodenough DA, Paul DL. Targeted ablation of connexin50 in mice results in microphthalmia and zonular pulverulent cataracts. J Cell Biol. 1998;143(3):815‐825
Willoughby CE, Arab S, Gandhi R, et al. A novel GJA8 mutation in an Iranian family with progressive autosomal dominant congenital nuclear cataract. J Med Genet. 2003;40(11):e124

Updated on November 30, 2020