Clinical Science
A recurrent mutation of CRYGD gene in a northern Chinese family with autosomal dominant congenital nuclear cataract
Xiaohui Zhang, Weihua Liu, Bing Dong, Jieqiong Chen, Yang Li
Published 2015-08-10
Cite as Chin J Exp Ophthalmol, 2015, 33(8): 722-726. DOI: 10.3760/cma.j.issn.2095-0160.2015.08.012
Abstract
BackgroundCongenital cataract is a major cause for blindness of childhood. Genetic gene mutation accounts for almost 1/3 of congenital cataract patients. The most common inheritance type is autosomal dominant congenital cataract (ADCC). Over 100 mutations in 26 genes have been found to be associated with ADCC.
ObjectiveThis study was to identify the disease-causing gene mutation in a family with ADCC.
MethodsThis study was approved by Ethic Committee of Beijing Tongren Hospital and followed Declaration of Helsinki. A northern Chinese family with autosomal dominant congenital nuclear cataract was entrolled in Beijing Tongren Hospital in January 2011. Ocular examinations were performed and periphery blood specimens were collected from each family member under the informed consent. Genomic DNA was extracted. Twenty-one microsatellite markers around 17 ADCC genes were selected for linkage analysis, and two-point LOD score was calculated. CRYGC gene and CRYGD gene were amplified and screened for mutations using direct sequencing. ProtScale software was used to analyze the changes of hydrophobicity of the mutated protein. Co-segregation of the observed change with the disease phenotype was further detected by restriction fragment length polymorphism (RFLP).
ResultsThis family included 20 members of 4 generations, and 9 patients were examined in serial 4 passages, which conformed to autosomal dominant inheritance pattern. Clinical examination revealed binocular congenital nuclear cataract in the 9 patients. Maximum two-point LOD score was 4. 68 at marker D2S325 (θ=0). A known T→C change at position 127 of cDNA sequence was found by mutations screening of CRYGD gene. ProtScale programs showed an obvious increase of the local hydrophobicity in the mutant protein. RFLP results indicated that this missense mutation co-segregated with affected members of the family, but was absent in unaffected members and 100 unrelated controls.
Conclusionsc. T127C mutation of CRYGD gene appears to be the molecular pathogenesis of this ADCC family. Aberrant structure of mutant CRYGD protein caused by hydrophobicity change may lead to opacification of lens.
Key words:
Cataract/congenital; Cataract/genetics; DNA mutational analysis; Lens nucleus, crystalline/pathology; Pedigree; gamma-Crystallin/genetics; Mutations; Chinese
Contributor Information
Xiaohui Zhang
Beijing Ophthalmology &
Visual Sciences Key Laboratory, Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing 100005, China
Weihua Liu
Bing Dong
Jieqiong Chen
Yang Li
