microRNAs and inherited retinal dystrophies
Year: 2015
Type: article
Abstract: Inherited retinal dystrophies (IRD) are a heterogeneous group of blinding diseases that affect more than 200,000 Americans and millions worldwide (1). Identification of genes that are responsible for IRD when defective is of great importance to the basic understanding as well as development of efficient gene diagnosis and treatment. Thus far, 272 genetic loci are linked to various forms of IRD; among these, 232 protein-coding genes have been identified to cause IRD when defective (RetNet, https://sph.uth.edu/Retnet, last updated April 29, 2015). microRNAs (miRNAs) are endogenous, small, noncoding, regulatory RNAs (2). Since their discovery in 1993 (3, 4), miRNAs have proven to play important roles in the fine-tuning of gene expression at posttranscriptional levels (2). In spite of their importance in gene-expression regulation, few mutations of individual miRNAs have been found to cause Mendelian inherited diseases in humans, raising doubts about their importance in normal development and functions, and whether mutations in a miRNA can have significant functional impact to cause Mendelian inherited diseases, including IRD. Recently, a point mutation in the seed sequence of miR-184 was reported to cause familial keratoconus with cataract (5) and an anterior-segment dysplasia syndrome with endothelial dystrophy, iris hypoplasia, congenital cataract, and stromal thinning (6), suggesting that miR-184 is required for anterior-segment development and function, and proving that mutations in an individual miRNA can cause inherited ocular disease in humans. In mice, Lumayag et al. demonstrated that inactivation of the miR-183/96/182 cluster gene causes syndromic IRD with multisensory defects (7), suggesting that defects in miRNA genes can cause IRD in mammals. However, until now, no mutations in miRNAs have been found to cause IRD in humans. In PNAS, Conte et al. report a dominant mutation in miR-204 that causes IRD associated with ocular coloboma in a large five-generation family (8). This …
Author: Shunbin Xu
Institutions: Wayne State University, Kresge Eye Institute
Language: English
Subfield: Ophthalmology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W1557411537