Limits...
A Novel Insertion Variant of CRYGD Is Associated with Congenital Nuclear Cataract in a Chinese Family.

Zhuang X, Wang L, Song Z, Xiao W - PLoS ONE (2015)

Bottom Line: A significantly reduced solubility was observed for this mutant.We have identified a novel mutation, c.451_452insGACT, in CRYGD, which is associated with nuclear cataract.The mutant protein, with loss of solubility and localization to the nucleus, is hypothesized to be the major cause of cataract in these patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Shengjing Hospital, China Medical University, Shenyang, China; Department of Ophthalmology, The Fourth People's Hospital of Shenyang, Shenyang, China.

ABSTRACT

Objective: To investigate a novel insertion variant of CRYGD identified in a Chinese family with nuclear congenital cataract.

Methods: A Chinese family with congenital nuclear cataract was recruited for the mutational screening of candidate genes by direct sequencing. Recombinant N-terminal Myc tagged wildtype or mutant CRYGD was expressed in HEK293T cells. The expression pattern, protein solubility and subcellular distribution were analyzed by western blotting and immunofluorescence.

Principal findings: A novel insertion variant, c.451_452insGACT, in CRYGD was identified in the patients. It causes a frameshift and a premature termination of the polypeptide to become Y151*. A significantly reduced solubility was observed for this mutant. Unlike wildtype CRYGD, which existed mainly in the cytoplasm, Y151* was mis-located in the nucleus.

Conclusions: We have identified a novel mutation, c.451_452insGACT, in CRYGD, which is associated with nuclear cataract. This is the first insertion mutation of CRYGD found to cause autosomal dominant congenital cataract. The mutant protein, with loss of solubility and localization to the nucleus, is hypothesized to be the major cause of cataract in these patients.

No MeSH data available.


Related in: MedlinePlus

The family with congenital nuclear cataract.(A) Pedigree of the Chinese family with autosomal dominant nuclear cataract. Squares and circles indicate males and females, respectively. Black symbols represent individuals with a cataract phenotype and open symbols represent unaffected individuals. The proband is marked by an arrow. The numbers of the participants in this study are indicated by red color. (B) Lens picture from the proband showed the opacities located in the lens nucleus and that the sutures were also involved (right eye).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4493073&req=5

pone.0131471.g001: The family with congenital nuclear cataract.(A) Pedigree of the Chinese family with autosomal dominant nuclear cataract. Squares and circles indicate males and females, respectively. Black symbols represent individuals with a cataract phenotype and open symbols represent unaffected individuals. The proband is marked by an arrow. The numbers of the participants in this study are indicated by red color. (B) Lens picture from the proband showed the opacities located in the lens nucleus and that the sutures were also involved (right eye).

Mentions: We collected blood samples from seven members (three affected and four unaffected) of a four-generation Han Chinese family with autosomal dominant nuclear cataract (Fig 1A) after obtaining informed consent and approval of the China Medical University Review Board. One hundred and three unrelated individuals were also recruited as study controls. Peripheral blood samples were collected for DNA analysis.


A Novel Insertion Variant of CRYGD Is Associated with Congenital Nuclear Cataract in a Chinese Family.

Zhuang X, Wang L, Song Z, Xiao W - PLoS ONE (2015)

The family with congenital nuclear cataract.(A) Pedigree of the Chinese family with autosomal dominant nuclear cataract. Squares and circles indicate males and females, respectively. Black symbols represent individuals with a cataract phenotype and open symbols represent unaffected individuals. The proband is marked by an arrow. The numbers of the participants in this study are indicated by red color. (B) Lens picture from the proband showed the opacities located in the lens nucleus and that the sutures were also involved (right eye).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493073&req=5

pone.0131471.g001: The family with congenital nuclear cataract.(A) Pedigree of the Chinese family with autosomal dominant nuclear cataract. Squares and circles indicate males and females, respectively. Black symbols represent individuals with a cataract phenotype and open symbols represent unaffected individuals. The proband is marked by an arrow. The numbers of the participants in this study are indicated by red color. (B) Lens picture from the proband showed the opacities located in the lens nucleus and that the sutures were also involved (right eye).
Mentions: We collected blood samples from seven members (three affected and four unaffected) of a four-generation Han Chinese family with autosomal dominant nuclear cataract (Fig 1A) after obtaining informed consent and approval of the China Medical University Review Board. One hundred and three unrelated individuals were also recruited as study controls. Peripheral blood samples were collected for DNA analysis.

Bottom Line: A significantly reduced solubility was observed for this mutant.We have identified a novel mutation, c.451_452insGACT, in CRYGD, which is associated with nuclear cataract.The mutant protein, with loss of solubility and localization to the nucleus, is hypothesized to be the major cause of cataract in these patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Shengjing Hospital, China Medical University, Shenyang, China; Department of Ophthalmology, The Fourth People's Hospital of Shenyang, Shenyang, China.

ABSTRACT

Objective: To investigate a novel insertion variant of CRYGD identified in a Chinese family with nuclear congenital cataract.

Methods: A Chinese family with congenital nuclear cataract was recruited for the mutational screening of candidate genes by direct sequencing. Recombinant N-terminal Myc tagged wildtype or mutant CRYGD was expressed in HEK293T cells. The expression pattern, protein solubility and subcellular distribution were analyzed by western blotting and immunofluorescence.

Principal findings: A novel insertion variant, c.451_452insGACT, in CRYGD was identified in the patients. It causes a frameshift and a premature termination of the polypeptide to become Y151*. A significantly reduced solubility was observed for this mutant. Unlike wildtype CRYGD, which existed mainly in the cytoplasm, Y151* was mis-located in the nucleus.

Conclusions: We have identified a novel mutation, c.451_452insGACT, in CRYGD, which is associated with nuclear cataract. This is the first insertion mutation of CRYGD found to cause autosomal dominant congenital cataract. The mutant protein, with loss of solubility and localization to the nucleus, is hypothesized to be the major cause of cataract in these patients.

No MeSH data available.


Related in: MedlinePlus