Two Pathogenic Gene Mutations Identified Associating with Congenital Cataract and Iris Coloboma Respectively in a Chinese Family

Bin Li; Bin Lu; Xuewen Guo; Shenghui Hu; Guihu Zhao; Weihong Huang; Jianzhong Hu; Kun Song

doi:10.1155/2020/7054315

Two Pathogenic Gene Mutations Identified Associating with Congenital Cataract and Iris Coloboma Respectively in a Chinese Family

J Ophthalmol. 2020 Feb 19:2020:7054315. doi: 10.1155/2020/7054315. eCollection 2020.

Authors

Bin Li^{1

2}, Bin Lu³, Xuewen Guo⁴, Shenghui Hu⁵, Guihu Zhao¹, Weihong Huang², Jianzhong Hu^{1

2

6}, Kun Song⁷

Affiliations

¹ National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
² Mobile Health Ministry of Education-China Mobile Joint Laboratory, Xiangya Hospital, Central South University, Changsha, China.
³ Department of Pathogen Biology, School of Basic Medical Sciences, Central South University, Changsha, China.
⁴ Department of Neurology, Liaocheng Dongchangfu People's Hospital, Liaocheng, China.
⁵ Department of Orthopaedics, Xiangya Second Hospital, Central South University, Changsha, China.
⁶ Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha, China.
⁷ Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, China.

Abstract

Purpose: To screen out pathogenic genes in a Chinese family with congenital cataract and iris coloboma. Material and Methods. A three-generation family with congenital cataract and iris coloboma from a Han ethnicity was recruited. DNA was extracted from peripheral blood samples collected from all individuals in the family. Whole exon sequencing was employed for screening the disease-causing gene mutations in the proband, and Sanger sequencing was used for other members of the family and a control group of 500 healthy individuals. Bioinformatics analysis and three-dimensional structure predictions were used to predict the impact of amino acid changes on protein structure and function.

Results: The candidate genes of cataract and iris coloboma were successfully screened out. A heterozygote mutation, CRYGD c.70C>A (p.P24T), was identified as cosegregating with congenital cataracts, while another heterozygous mutation, WFS1 c.1514G>C (p.C505S), which had not been reported previously, cosegregated with congenital iris coloboma. Bioinformatic analyses and three-dimensional structure prediction proved that the three-dimensional structures of WFS1 c.1514G>C (p.C505S), which had not been reported previously, cosegregated with congenital iris coloboma. Bioinformatic analyses and three-dimensional structure prediction proved that the three-dimensional structures of CRYGD c.70C>A (p.P24T), was identified as cosegregating with congenital cataracts, while another heterozygous mutation.

Conclusions: We report a novel mutation, WFS1 p.C505S, and a known mutation, CRYGD p.P24T, that cosegregate with iris coloboma and congenital cataract, respectively, in a Chinese family. This is the first time the association of WFS1 p.C505S with iris coloboma has been demonstrated, although CRYGD p.P24T has been widely reported as being associated with congenital cataract, especially in the Eastern Asian population. These findings may have future therapeutic benefit for the diagnosis of iris coloboma and congenital cataract. The results may also be relevant in further studies aiming to investigate the molecular pathogenesis of iris coloboma and congenital cataract.WFS1 c.1514G>C (p.C505S), which had not been reported previously, cosegregated with congenital iris coloboma. Bioinformatic analyses and three-dimensional structure prediction proved that the three-dimensional structures of CRYGD c.70C>A (p.P24T), was identified as cosegregating with congenital cataracts, while another heterozygous mutation, WFS1 c.1514G>C (p.C505S), which had not been reported previously, cosegregated with congenital iris coloboma. Bioinformatic analyses and three-dimensional structure prediction proved that the three-dimensional structures of CRYGD c.70C>A (p.P24T), was identified as cosegregating with congenital cataracts, while another heterozygous mutation.