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Exome sequencing identifies a novel mutation in GJA8 associated with inherited cataract in a Chinese family

  • Genetics
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An Erratum to this article was published on 29 November 2016

Abstract

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.

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Acknowledgments

Authors’ contributions: MR and XGY for bioinformatics analysis and writing of the manuscript. XJD and JAX for discussion and comments on an earlier version of the manuscript. All authors read and approved the final manuscript.

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Authors and Affiliations

  1. Department of Ophthalmology, Xi’an fourth hospital, Xi’an, Shaanxi Province, People’s Republic of China

    Mei Ren, Xin Guang Yang, Xiao Jie Dang & Jin An Xiao

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  1. Mei Ren
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  2. Xin Guang Yang
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  3. Xiao Jie Dang
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  4. Jin An Xiao
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Correspondence to Xin Guang Yang.

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Funding

Xi’an science and technology bureau provided financial support in the form of science and technology project of Xi’an funding (HM1116 (1)). The sponsor had no role in the design or conduct of this research.

Competing interests

All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study. Additional informed consent was obtained from all individual participants for whom identifying information is included in this article.

Additional information

An erratum to this article is available at http://dx.doi.org/10.1007/s00417-016-3557-x.

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Ren, M., Yang, X.G., Dang, X.J. et al. Exome sequencing identifies a novel mutation in GJA8 associated with inherited cataract in a Chinese family. Graefes Arch Clin Exp Ophthalmol 255, 141–151 (2017). https://doi.org/10.1007/s00417-016-3513-9

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