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Case Reports
. 2020 Oct;8(10):e1436.
doi: 10.1002/mgg3.1436. Epub 2020 Jul 23.

Increased hydrophobicity of CRYGD p.(Ala159ProfsTer9): Suspected cause of congenital cataracts in a large Chinese family

Meina Lin  1 , Ying Jin  1 , Xinren Chen  1 , Yu Sui  1 , Yan Li  1 , Huan Li  1 , Xiang Ni  1 , Ning Zhao  1 , Yongping Lu  1 , Miao Jiang  1
Affiliations
Case Reports

Increased hydrophobicity of CRYGD p.(Ala159ProfsTer9): Suspected cause of congenital cataracts in a large Chinese family

Meina Lin et al. Mol Genet Genomic Med. 2020 Oct.

Abstract

Objective: This study aimed to identify the disease-causing mutation of congenital cataract disease in a large northeastern Chinese family.

Materials and methods: The subjects' peripheral blood was collected, their genomic DNA was extracted, mutation screening of candidate genes was performed using polymerase chain reaction, and the amplified products were sequenced. Recombinant C-terminal enhanced green fluorescent protein-tagged wild-type or mutant CRYGD was expressed in HEK293T cells, and the expression pattern was observed under a fluorescence microscope. The CRYGD protein mutation was analyzed via bioinformatics analysis.

Results: c.475delG, a novel frameshift mutation in CRYGD, was identified in the affected family members. This mutation causes premature termination of the polypeptide, resulting in truncated p.(Ala159ProfsTer9). According to the bioinformatics analysis results, compared with wild-type CRYGD, p.(Ala159ProfsTer9) exhibits significantly decreased hydrophilicity. Fluorescence microscopy revealed that p.(Ala159ProfsTer9) aggregates in the cell in the form of granular deposits.

Conclusion: In this study, the novel frameshift mutation c.475delG, p.(Ala159ProfsTer9) in CRYGD was identified to cause congenital cataracts in a large Chinese family; increased hydrophobicity of p.(Ala159ProfsTer9) protein may be the underlying mechanism.

Keywords: CRYGD; bioinformatics analysis; c.475delG mutation; congenital cataract; hydrophobicity; p.(Ala159ProfsTer9).

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Conflict of interest statement

No conflict of interest exists in the submission of this manuscript, and the manuscript is approved by all authors for publication.

Figures

Figure 1
Figure 1
Pedigree of the Chinese family with congenital cataracts. (a) Across five generations, 18 members were affected with bilateral congenital nuclear cataracts. (b) Sanger sequence of exon 3 of CRYGD in the proband (Ⅲ12) and an unaffected member (Ⅳ9). The heterozygous c.475delG in the affected member. (c) HRM showed different plots of wild‐type samples and the various mutants; the affected individuals were represented by red lines and control by gray lines. (d) Protein alignment of mammalian samples showing that the regions surrounding the mutation are highly conserved. Numbers on the left and right indicate the position of this fragment. The position of the mutant is marked by an asterisk (*). The reference sequence of the CRYGD gene was NM_006891.3
Figure 2
Figure 2
Bioinformatics analysis of the mutant CRYGD p.(Ala159ProfsTer9). (a) Diagrammatic scheme of the functional domain of CRYGD and p.(Ala159ProfsTer9) protein. (b) The tertiary structure of CRYGD and p.(Ala159ProfsTer9) protein. (c) The predicted secondary structure showing the reduced extended strand and random coil in the mutant. (d) The predicted secondary structure showing the changed alpha‐helices and beta‐strands in the mutant. (e) The predicted hydrophobic surface and amino changes in the mutant
Figure 3
Figure 3
Localization of EGFP‐tagged wild‐type or p.(Ala159ProfsTer9) CRYGD in HEK293T cells. Green fluorescence showed that mutant CRYGD was mainly localized in the cell in the form of granular deposits
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