Exome sequencing identifies a novel mutation in GJA8 associated with inherited cataract in a Chinese family.
BACKGROUND
Congenital cataract is a clinical and genetic heterogeneous group of eye disorders that causes visual impairment and childhood blindness. In this study, a Chinese family with congenital cataract is studied.


METHODS
In order to identify the genetic defects which were associated with congenital cataract, a whole-exome sequencing approach is performed to screen for the potential mutation-causing disease.


RESULTS
The result revealed a novel heterozygous mutation (c.433G > T; p.G145W) in exon 2 the of GJA8 gene, which can be detected in all affected individuals, but not the unaffected family members. Meanwhile, this novel mutation cannot be retrieved in 100 healthy local Chinese controls and five other SNPs databases (dbSNP, ESP, ExAC, HTD and HGVD). Moreover, p.G145W was predicted as a mutation with pathogenicity by using bioinformatics methods, including PolyPhen-2, SIFT, PROVEAN, SNPs3D and the mutation significance cutoff (MSC). However, molecular function analysis of this novel mutation (p.G145W, GJA8) indicated that it did not affect the subcellular distributions and the trafficking of GJA8 protein to the plasma membrane. The truth of pathogenic significance with this novel mutation in GJA8 gene needed to be further studied.


CONCLUSIONS
The c.433G > T (p.G145W) mutation in the GJA8 gene was first reported to our best knowledge. The results of our study would further broaden the mutation spectrum of GJA8 associated with congenital cataract.
['Ren|Mei|M|', 'Yang|Xin Guang|XG|', 'Dang|Xiao Jie|XJ|', 'Xiao|Jin An|JA|']
D000293:Adolescent D000328:Adult D002386:Cataract D002648:Child D002675:Child, Preschool D017630:Connexins D004247:DNA D004252:DNA Mutational Analysis D059472:Exome D005260:Female D006579:Heterozygote D006801:Humans D008297:Male D008562:Membrane Glycoproteins D008875:Middle Aged D009154:Mutation D010375:Pedigree D055815:Young Adult
GJA8 Congenital cataract Autosomal dominant Exome-sequencing