Open AccessA Novel Insertion Variant of CRYGD Is Associated with Congenital Nuclear Cataract in a Chinese Family
Author(s) -
Xiaotong Zhuang,
Lianqing Wang,
Zixun Song,
Wei Xiao
Publication year - 2015
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0131471
Subject(s) - frameshift mutation , mutant , mutation , biology , genetics , wild type , microbiology and biotechnology , nuclear localization sequence , mutant protein , compound heterozygosity , cytoplasm , gene
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.