Two Pathogenic Gene Mutations Identified Associating with Congenital Cataract and Iris Coloboma Respectively in a Chinese Family
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 in...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Journal of Ophthalmology |
| Online Access: | http://dx.doi.org/10.1155/2020/7054315 |
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| author | Bin Li Bin Lu Xuewen Guo Shenghui Hu Guihu Zhao Weihong Huang Jianzhong Hu Kun Song |
| author_facet | Bin Li Bin Lu Xuewen Guo Shenghui Hu Guihu Zhao Weihong Huang Jianzhong Hu Kun Song |
| author_sort | Bin Li |
| collection | DOAJ |
| description | 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 p.C505S and CRYGD p.P24T changed markedly and may contribute significantly to iris coloboma and congenital cataract, respectively. 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. |
| format | Article |
| id | doaj-art-3b5adc6eaa5b4ba0af80c8c8317ba83a |
| institution | OA Journals |
| issn | 2090-004X 2090-0058 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Ophthalmology |
| spelling | doaj-art-3b5adc6eaa5b4ba0af80c8c8317ba83a2025-08-20T02:39:07ZengWileyJournal of Ophthalmology2090-004X2090-00582020-01-01202010.1155/2020/70543157054315Two Pathogenic Gene Mutations Identified Associating with Congenital Cataract and Iris Coloboma Respectively in a Chinese FamilyBin Li0Bin Lu1Xuewen Guo2Shenghui Hu3Guihu Zhao4Weihong Huang5Jianzhong Hu6Kun Song7National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Pathogen Biology, School of Basic Medical Sciences, Central South University, Changsha, ChinaDepartment of Neurology, Liaocheng Dongchangfu People's Hospital, Liaocheng, ChinaDepartment of Orthopaedics, Xiangya Second Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, ChinaMobile Health Ministry of Education—China Mobile Joint Laboratory, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, ChinaPurpose. 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 p.C505S and CRYGD p.P24T changed markedly and may contribute significantly to iris coloboma and congenital cataract, respectively. 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.http://dx.doi.org/10.1155/2020/7054315 |
| spellingShingle | Bin Li Bin Lu Xuewen Guo Shenghui Hu Guihu Zhao Weihong Huang Jianzhong Hu Kun Song Two Pathogenic Gene Mutations Identified Associating with Congenital Cataract and Iris Coloboma Respectively in a Chinese Family Journal of Ophthalmology |
| title | Two Pathogenic Gene Mutations Identified Associating with Congenital Cataract and Iris Coloboma Respectively in a Chinese Family |
| title_full | Two Pathogenic Gene Mutations Identified Associating with Congenital Cataract and Iris Coloboma Respectively in a Chinese Family |
| title_fullStr | Two Pathogenic Gene Mutations Identified Associating with Congenital Cataract and Iris Coloboma Respectively in a Chinese Family |
| title_full_unstemmed | Two Pathogenic Gene Mutations Identified Associating with Congenital Cataract and Iris Coloboma Respectively in a Chinese Family |
| title_short | Two Pathogenic Gene Mutations Identified Associating with Congenital Cataract and Iris Coloboma Respectively in a Chinese Family |
| title_sort | two pathogenic gene mutations identified associating with congenital cataract and iris coloboma respectively in a chinese family |
| url | http://dx.doi.org/10.1155/2020/7054315 |
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