Novel MIP gene mutation causes autosomal-dominant congenital cataract
AIM: To identify disease-causative mutations in families with congenital cataract. METHODS: Two Chinese families with autosomal-dominant congenital cataract (ADCC) were recruited and underwent comprehensive eye examinations. Gene panel next-generation sequencing of common pathogenic genes of congeni...
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| Format: | Article |
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Press of International Journal of Ophthalmology (IJO PRESS)
2024-03-01
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| Series: | International Journal of Ophthalmology |
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| Online Access: | http://ies.ijo.cn/en_publish/2024/3/20240306.pdf |
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| author | Jing-Lan Ni Hua-Ming Wen Xiao-Sheng Huang Qian-Wen Li Jia-Min Cai Bao-Jian Fan Jun Zhao |
| author_facet | Jing-Lan Ni Hua-Ming Wen Xiao-Sheng Huang Qian-Wen Li Jia-Min Cai Bao-Jian Fan Jun Zhao |
| author_sort | Jing-Lan Ni |
| collection | DOAJ |
| description | AIM: To identify disease-causative mutations in families with congenital cataract. METHODS: Two Chinese families with autosomal-dominant congenital cataract (ADCC) were recruited and underwent comprehensive eye examinations. Gene panel next-generation sequencing of common pathogenic genes of congenital cataract was performed in the proband of each family. Sanger sequencing was used to valid the candidate gene mutations and sequence the other family members for co-segregation analysis. The effect of sequence changes on protein structure and function was predicted through bioinformatics analysis. Major intrinsic protein (MIP)-wildtype and MIP-G29R plasmids were constructed and microinjected into zebrafish single-cell stage embryos. Zebrafish embryonic lens phenotypes were screened using confocal microscopy. RESULTS: A novel heterozygous mutation (c.85G>A; p.G29R) in the MIP gene was identified in the proband of one family. A known heterozygous mutation (c.97C>T; p.R33C; rs864309693) in MIP was found in the proband of another family. In-silico prediction indicated that the novel mutation might affect the MIP protein function. Zebrafish embryonic lens was uniformly transparent in both wild-type PCS2+MIP and mutant PCS2+MIP. CONCLUSION: Two missense mutations in the MIP gene in Chinese cataract families are identified, and one of which is novel. These findings expand the genetic spectrum of MIP mutations associated with cataracts. The functional studies suggest that the novel MIP mutation might not be a gain-of-function but a loss-of-function mutation. |
| first_indexed | 2024-03-07T21:22:52Z |
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| id | doaj.art-5556a235b19246048a61a3c3eb41a3fd |
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| issn | 2222-3959 2227-4898 |
| language | English |
| last_indexed | 2024-03-07T21:22:52Z |
| publishDate | 2024-03-01 |
| publisher | Press of International Journal of Ophthalmology (IJO PRESS) |
| record_format | Article |
| series | International Journal of Ophthalmology |
| spelling | doaj.art-5556a235b19246048a61a3c3eb41a3fd2024-02-27T08:51:41ZengPress of International Journal of Ophthalmology (IJO PRESS)International Journal of Ophthalmology2222-39592227-48982024-03-0117345446510.18240/ijo.2024.03.0620240306Novel MIP gene mutation causes autosomal-dominant congenital cataractJing-Lan Ni0Hua-Ming Wen1Xiao-Sheng Huang2Qian-Wen Li3Jia-Min Cai4Bao-Jian Fan5Jun Zhao6Jun Zhao. Department of Ophthalmology, Shenzhen People's Hospital (the Second Clinical Medical College, Jinan University; the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, Guangdong Province, China. doctorzhaojun@163.com; Hua-Ming Wen. Department of Ophthalmology, Dongguan Chang'an Hospital, Dongguan 523843, Guangdong Province, China. wenruxiang555@163.comDepartment of Ophthalmology, Dongguan Chang'an Hospital, Dongguan 523843, Guangdong Province, ChinaShenzhen Eye Hospital Affiliated to Jinan University, Shenzhen Eye Institute, Shenzhen 518040, Guangdong Province, ChinaDepartment of Oral & Maxillofacial Surgery, Shenzhen Stomatology Hospital Affiliated to Shenzhen University, Shenzhen 518040, Guangdong Province, ChinaShenzhen Eye Hospital Affiliated to Jinan University, Shenzhen Eye Institute, Shenzhen 518040, Guangdong Province, ChinaDepartment of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston 02114, Massachusetts, USADepartment of Ophthalmology, Shenzhen People's Hospital (the Second Clinical Medical College, Jinan UniversityAIM: To identify disease-causative mutations in families with congenital cataract. METHODS: Two Chinese families with autosomal-dominant congenital cataract (ADCC) were recruited and underwent comprehensive eye examinations. Gene panel next-generation sequencing of common pathogenic genes of congenital cataract was performed in the proband of each family. Sanger sequencing was used to valid the candidate gene mutations and sequence the other family members for co-segregation analysis. The effect of sequence changes on protein structure and function was predicted through bioinformatics analysis. Major intrinsic protein (MIP)-wildtype and MIP-G29R plasmids were constructed and microinjected into zebrafish single-cell stage embryos. Zebrafish embryonic lens phenotypes were screened using confocal microscopy. RESULTS: A novel heterozygous mutation (c.85G>A; p.G29R) in the MIP gene was identified in the proband of one family. A known heterozygous mutation (c.97C>T; p.R33C; rs864309693) in MIP was found in the proband of another family. In-silico prediction indicated that the novel mutation might affect the MIP protein function. Zebrafish embryonic lens was uniformly transparent in both wild-type PCS2+MIP and mutant PCS2+MIP. CONCLUSION: Two missense mutations in the MIP gene in Chinese cataract families are identified, and one of which is novel. These findings expand the genetic spectrum of MIP mutations associated with cataracts. The functional studies suggest that the novel MIP mutation might not be a gain-of-function but a loss-of-function mutation.http://ies.ijo.cn/en_publish/2024/3/20240306.pdfcongenital cataractmajor intrinsic proteinmissense mutationzebrafish model |
| spellingShingle | Jing-Lan Ni Hua-Ming Wen Xiao-Sheng Huang Qian-Wen Li Jia-Min Cai Bao-Jian Fan Jun Zhao Novel MIP gene mutation causes autosomal-dominant congenital cataract International Journal of Ophthalmology congenital cataract major intrinsic protein missense mutation zebrafish model |
| title | Novel MIP gene mutation causes autosomal-dominant congenital cataract |
| title_full | Novel MIP gene mutation causes autosomal-dominant congenital cataract |
| title_fullStr | Novel MIP gene mutation causes autosomal-dominant congenital cataract |
| title_full_unstemmed | Novel MIP gene mutation causes autosomal-dominant congenital cataract |
| title_short | Novel MIP gene mutation causes autosomal-dominant congenital cataract |
| title_sort | novel mip gene mutation causes autosomal dominant congenital cataract |
| topic | congenital cataract major intrinsic protein missense mutation zebrafish model |
| url | http://ies.ijo.cn/en_publish/2024/3/20240306.pdf |
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