Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2016
Exome sequencing identifies a novel mutation in GJA8 associated with inherited cataract in a Chinese family.
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Ren Mei, Yang Xin Guang, Dang Xiao Jie, Xiao Jin An
Аннотация
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.
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.