Further evidence for P59L mutation in GJA3 associated with autosomal dominant congenital cataract

Context:Congenital cataracts are one of the common eye disorders leading to visual impairment or blindness in children worldwide. We found a Chinese family with autosomal dominant pulverulent cataract.Aims:To identify the pathogenic gene mutation in a Chinese family with autosomal dominant inherited pulverulent cataract.Results:By sequencing the encoding regions of the candidate genes, a missense mutation (c. 176C>T) was detected in gap junction protein alpha 3 genes (GJA3), which resulted in the substitution of highly conserved proline by leucine at codon 59 (p.P59L). The mutation co-segregated with all patients and was absent in 100 normal Chinese controls.Conclusions:The study identified a missense mutation (c. 176C>T) in GJA3 gene associated with autosomal dominant congenital pulverulent cataract in a Chinese family. It gave further evidence of phenotype heterogeneity for P59L mutation in GJA3 associated with congenital cataract.Key words: Congenital cataract, GJA3, mutationCongenital cataracts are one of the common eye disorders leading to visual impairment or blindness in children worldwide. Congenital cataract may be inherited or familial, either as an isolated form or as a part of a syndrome, such as Nance-Horan syndrome. Along with the development of molecular genetics, more than 20 genes have been identified to be involved in isolated cataract formation.[1]The lens is an avascular organ which is composed of a monolayer of cuboidal epithelial cells covering the anterior surface of elongated fibers, which transmits and focuses light images onto the retina. Interior fiber cells, including both primary and secondary fiber cells, undergo a maturation process to eliminate all intracellular organelles, such as the nucleus, mitochondria, endoplasmic reticulum, and Golgi apparatus, thereby minimizing light scattering and ensuring lens transparency.[2] The interior mature fibers have an extremely low metabolic activity and depend mainly on the epithelium and peripheral differential fibers for maintenance. Therefore, the lens has developed as a syncytium and a sophisticated cell-cell communication network, which facilitates both an active metabolism and transport of small metabolites, such as ions, water, and secondary messengers.[3] Intercellular gap junction channels provide pathways for metabolic and electrical coupling between cells in the lens. Gap junction channels consist of connexin (Cx) protein subunits. To date, many Cx genes have been found in the mouse genome and the human genome.[4] Mutations in Cx have been identified with various inherited diseases,[5] including Cx32 mutation in X-linked Charcot-Marie tooth disease, Cx26 and Cx30 mutations in deafness and skin diseases, Cx46 and Cx50 mutations in hereditary cataracts, and Cx31 mutation in erythrokeratodermia variabilis and hearing impairment with/without peripheral neuropathy.In our study, we found a missense mutation the substitution of proline to leucine of the codon 59 (p.P59L) in GJA3 (Cx46) associated with autosomal dominant pulverulent cataract in a Chinese family.