Variant Landscape of 15 Genes Involved in Corneal Dystrophies: Report of 30 Families and Comprehensive Analysis of the Literature
Corneal dystrophies (CDs) represent a group of inherited diseases characterized by the progressive deposit of abnormal materials in the cornea. This study aimed to describe the variant landscape of 15 genes responsible for CDs based on a cohort of Chinese families and a comparative analysis of liter...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-03-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/5/5012 |
| _version_ | 1797615096779767808 |
|---|---|
| author | Di Zhu Junwen Wang Yingwei Wang Yi Jiang Shiqiang Li Xueshan Xiao Panfeng Wang Qingjiong Zhang |
| author_facet | Di Zhu Junwen Wang Yingwei Wang Yi Jiang Shiqiang Li Xueshan Xiao Panfeng Wang Qingjiong Zhang |
| author_sort | Di Zhu |
| collection | DOAJ |
| description | Corneal dystrophies (CDs) represent a group of inherited diseases characterized by the progressive deposit of abnormal materials in the cornea. This study aimed to describe the variant landscape of 15 genes responsible for CDs based on a cohort of Chinese families and a comparative analysis of literature reports. Families with CDs were recruited from our eye clinic. Their genomic DNA was analyzed using exome sequencing. The detected variants were filtered using multi-step bioinformatics and confirmed using Sanger sequencing. Previously reported variants in the literature were summarized and evaluated based on the gnomAD database and in-house exome data. In 30 of 37 families with CDs, 17 pathogenic or likely pathogenic variants were detected in 4 of the 15 genes, including <i>TGFBI</i>, <i>CHST6</i>, <i>SLC4A11</i>, and <i>ZEB1</i>. A comparative analysis of large datasets revealed that 12 of the 586 reported variants are unlikely causative of CDs in monogenic mode, accounting for 61 of 2933 families in the literature. Of the 15 genes, the gene most frequently implicated in CDs was <i>TGFBI</i> (1823/2902, 62.82% of families), followed by <i>CHST6</i> (483/2902, 16.64%) and <i>SLC4A11</i> (201/2902, 6.93%). This study presents, for the first time, the landscape of pathogenic and likely pathogenic variants in the 15 genes responsible for CDs. Awareness of frequently misinterpreted variants, such as c.1501C>A, p.(Pro501Thr) in <i>TGFBI</i>, is crucial in the era of genomic medicine. |
| first_indexed | 2024-03-11T07:21:40Z |
| format | Article |
| id | doaj.art-8925d02020774f3e9f000e4be1558078 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T07:21:40Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-8925d02020774f3e9f000e4be15580782023-11-17T07:56:33ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01245501210.3390/ijms24055012Variant Landscape of 15 Genes Involved in Corneal Dystrophies: Report of 30 Families and Comprehensive Analysis of the LiteratureDi Zhu0Junwen Wang1Yingwei Wang2Yi Jiang3Shiqiang Li4Xueshan Xiao5Panfeng Wang6Qingjiong Zhang7State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou 510060, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou 510060, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou 510060, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou 510060, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou 510060, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou 510060, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou 510060, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou 510060, ChinaCorneal dystrophies (CDs) represent a group of inherited diseases characterized by the progressive deposit of abnormal materials in the cornea. This study aimed to describe the variant landscape of 15 genes responsible for CDs based on a cohort of Chinese families and a comparative analysis of literature reports. Families with CDs were recruited from our eye clinic. Their genomic DNA was analyzed using exome sequencing. The detected variants were filtered using multi-step bioinformatics and confirmed using Sanger sequencing. Previously reported variants in the literature were summarized and evaluated based on the gnomAD database and in-house exome data. In 30 of 37 families with CDs, 17 pathogenic or likely pathogenic variants were detected in 4 of the 15 genes, including <i>TGFBI</i>, <i>CHST6</i>, <i>SLC4A11</i>, and <i>ZEB1</i>. A comparative analysis of large datasets revealed that 12 of the 586 reported variants are unlikely causative of CDs in monogenic mode, accounting for 61 of 2933 families in the literature. Of the 15 genes, the gene most frequently implicated in CDs was <i>TGFBI</i> (1823/2902, 62.82% of families), followed by <i>CHST6</i> (483/2902, 16.64%) and <i>SLC4A11</i> (201/2902, 6.93%). This study presents, for the first time, the landscape of pathogenic and likely pathogenic variants in the 15 genes responsible for CDs. Awareness of frequently misinterpreted variants, such as c.1501C>A, p.(Pro501Thr) in <i>TGFBI</i>, is crucial in the era of genomic medicine.https://www.mdpi.com/1422-0067/24/5/5012corneal dystrophiesvariants spectrum<i>TGFBI</i><i>CHST6</i><i>SLC4A11</i><i>ZEB1</i> |
| spellingShingle | Di Zhu Junwen Wang Yingwei Wang Yi Jiang Shiqiang Li Xueshan Xiao Panfeng Wang Qingjiong Zhang Variant Landscape of 15 Genes Involved in Corneal Dystrophies: Report of 30 Families and Comprehensive Analysis of the Literature International Journal of Molecular Sciences corneal dystrophies variants spectrum <i>TGFBI</i> <i>CHST6</i> <i>SLC4A11</i> <i>ZEB1</i> |
| title | Variant Landscape of 15 Genes Involved in Corneal Dystrophies: Report of 30 Families and Comprehensive Analysis of the Literature |
| title_full | Variant Landscape of 15 Genes Involved in Corneal Dystrophies: Report of 30 Families and Comprehensive Analysis of the Literature |
| title_fullStr | Variant Landscape of 15 Genes Involved in Corneal Dystrophies: Report of 30 Families and Comprehensive Analysis of the Literature |
| title_full_unstemmed | Variant Landscape of 15 Genes Involved in Corneal Dystrophies: Report of 30 Families and Comprehensive Analysis of the Literature |
| title_short | Variant Landscape of 15 Genes Involved in Corneal Dystrophies: Report of 30 Families and Comprehensive Analysis of the Literature |
| title_sort | variant landscape of 15 genes involved in corneal dystrophies report of 30 families and comprehensive analysis of the literature |
| topic | corneal dystrophies variants spectrum <i>TGFBI</i> <i>CHST6</i> <i>SLC4A11</i> <i>ZEB1</i> |
| url | https://www.mdpi.com/1422-0067/24/5/5012 |
| work_keys_str_mv | AT dizhu variantlandscapeof15genesinvolvedincornealdystrophiesreportof30familiesandcomprehensiveanalysisoftheliterature AT junwenwang variantlandscapeof15genesinvolvedincornealdystrophiesreportof30familiesandcomprehensiveanalysisoftheliterature AT yingweiwang variantlandscapeof15genesinvolvedincornealdystrophiesreportof30familiesandcomprehensiveanalysisoftheliterature AT yijiang variantlandscapeof15genesinvolvedincornealdystrophiesreportof30familiesandcomprehensiveanalysisoftheliterature AT shiqiangli variantlandscapeof15genesinvolvedincornealdystrophiesreportof30familiesandcomprehensiveanalysisoftheliterature AT xueshanxiao variantlandscapeof15genesinvolvedincornealdystrophiesreportof30familiesandcomprehensiveanalysisoftheliterature AT panfengwang variantlandscapeof15genesinvolvedincornealdystrophiesreportof30familiesandcomprehensiveanalysisoftheliterature AT qingjiongzhang variantlandscapeof15genesinvolvedincornealdystrophiesreportof30familiesandcomprehensiveanalysisoftheliterature |