A Novel Mutation p.S93R in CRYBB1 Associated with Dominant Congenital Cataract and Microphthalmia

ABSTRACT

Purpose: To identify the pathogenetic mutations in a four-generation Chinese family with dominant congenital cataracts and microphthalmia.

Methods: A four-generation Chinese family with dominant congenital cataracts were recruited. Genomic DNAs were collected from their peripheral blood leukocytes and subjected to whole exome sequencing. The genetic mutations were identified by bioinformatic analyses and verified by Sanger sequencing.

Results: Whole exome sequencing revealed a c.279C>G point mutation in the CRYBB1 gene which was further verified by Sanger sequencing. The nucleotide replacement results in a novel mutation p.S93R in a conserved residue of βB1 crystallin which is predicted to disrupt normal βB1 structure and function.

Conclusions: We identified a novel missense mutation p.S93R in CRYBB1 in a Chinese family with autosomal dominant congenital cataracts and microphthalmia. This serine residue is extremely conserved evolutionarily in more than 50 βγ-crystallins of many species. These data will be very helpful to further understand the structural and functional features of crystallins.

KEYWORDS:

• Crystallin
• CRYBB1
• cataract
• congenital
• dominant
• mutation
• microphthalmia
• microcornea

Acknowledgments

We thank the Chinese family for participating in this study. We thank many online databases and resources for providing data and tools.

Author contributions

KJ, MX & MZ designed and advised the project; AJ, YZ, DX and KJ collected data; KJ analyzed the data; KJ, MX & MZ wrote the manuscript.

Financial interests

The authors declare no financial interests.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This work is supported by funds from the National Key R&D Program of China [2017YFA0104100]; National Basic Research Program (973 Program) of China [2015CB964600]; National Natural Science Foundation of China [81670862, 81721003 and 31871497]; Natural Science Foundation of Guangdong Province [2014A030313013]; Science and Technology Program of Guangzhou, China [201904010358 and 201904020036]; and the Fundamental Research Funds of the State Key Laboratory of Ophthalmology, Sun Yat-sen University.