Wen Sun1, Jiawei Xu1, Yangshun Gu1, Chixin Du2. 1. Department of Ophthalmology, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, 310003, Hangzhou, China. 2. Department of Ophthalmology, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, 310003, Hangzhou, China. duchixin@zju.edu.cn.
Abstract
BACKGROUND: Genetic factors play an essential role in the development of cataracts, and the major intrinsic protein (MIP) gene is a type of causative genes. Our study aims to discuss the current research progress of MIP genes responsible for cataractogenesis in DNA and protein levels, which is essential in achieving a response to the molecular deficiencies and pathophysiologic features of cataract. METHODS: We developed a search strategy using a combination of the words "Cataract", "Mutation", "MIP gene", and "AQP0" to identify all articles from PubMed, Web of Science, Scopus, and Google Scholar up to December 2019. To find more articles and to ensure that databases were thoroughly searched, the reference lists of selected items were also reviewed. RESULTS: A total of 29 MIP gene mutations causing congenital cataract were obtained by searching these databases and analyzing the results of genetic mutation pathogenicity prediction software tools; most of them caused amino acid codon changes in the H4, H5, H6, C-TIDs, and loop C in the structure of the MIP protein. However, there was no clear causality between lens morphology, phenotypes, and genotypes. The genotype TC in polymorphism c.-4T > C and haplotype CCG of rs2269348, c.-4T > C, and rs74641138 in MIP may attach an additional genetic risk factor for age-related cataract. CONCLUSION: These single-base mutations and single nucleotide polymorphisms might be importantly involved in the pathogenesis of congenital cataract and age-related cataract, respectively. This review provides a significant reference for clinical trials and theoretical studies.
BACKGROUND: Genetic factors play an essential role in the development of cataracts, and the major intrinsic protein (MIP) gene is a type of causative genes. Our study aims to discuss the current research progress of MIP genes responsible for cataractogenesis in DNA and protein levels, which is essential in achieving a response to the molecular deficiencies and pathophysiologic features of cataract. METHODS: We developed a search strategy using a combination of the words "Cataract", "Mutation", "MIP gene", and "AQP0" to identify all articles from PubMed, Web of Science, Scopus, and Google Scholar up to December 2019. To find more articles and to ensure that databases were thoroughly searched, the reference lists of selected items were also reviewed. RESULTS: A total of 29 MIP gene mutations causing congenital cataract were obtained by searching these databases and analyzing the results of genetic mutation pathogenicity prediction software tools; most of them caused amino acid codon changes in the H4, H5, H6, C-TIDs, and loop C in the structure of the MIP protein. However, there was no clear causality between lens morphology, phenotypes, and genotypes. The genotype TC in polymorphism c.-4T > C and haplotype CCG of rs2269348, c.-4T > C, and rs74641138 in MIP may attach an additional genetic risk factor for age-related cataract. CONCLUSION: These single-base mutations and single nucleotide polymorphisms might be importantly involved in the pathogenesis of congenital cataract and age-related cataract, respectively. This review provides a significant reference for clinical trials and theoretical studies.
Entities:
Keywords:
Cataract; Gene mutation; Major intrinsic protein; Single nucleotide polymorphisms
Authors: Jessica B Martin; Kenneth Herman; Nathalie S Houssin; Wade Rich; Matthew A Reilly; Timothy F Plageman Journal: Front Cell Dev Biol Date: 2022-07-06