Mutation Screening in the miR-183/96/182 Cluster in Patients With Inherited Retinal Dystrophy

Frontiers in Cell and Developmental Biology

卷:8

Joanne Choi¹  Eric Mishulin²  William J. Garcia³  Ali Harajli⁴  Chafic Dahabra⁴  Ardian Coku⁵  Chithra K. Muraleedharan⁵  Shunbin Xu⁵  Kerry Goetz⁶  Weifeng Li⁷  David Birch⁸  Kaylie Webb⁸ 

[1] Class of 2020, School of Medicine, Wayne State University, Detroit, MI, United States;

[2] College of Literature, Science, and the Arts, University of Michigan, Ann Arbor, MI, United States;

[3] College of Natural Science, Michigan State University, East Lansing, MI, United States;

[4] Department of Biological Sciences, Wayne State University, Detroit, MI, United States;

[5] Department of Ophthalmology, Visual and Anatomical Sciences, School of Medicine, Wayne State University, Detroit, MI, United States;

[6] National Eye Institute, National Institutes of Health, Bethesda, MD, United States;

[7] Peking Union Medical College, Beijing, China;

[8] Retina Foundation of the Southwest, Dallas, TX, United States;

关键词: microRNA;    miR-183/96/182 cluster;    inherited retinal dystrophy;    sequence variants;    susceptibility;   

DOI  :  10.3389/fcell.2020.619641

来源: DOAJ

【 摘 要 】

Inherited retinal dystrophy (IRD) is a heterogenous blinding eye disease and affects more than 200,000 Americans and millions worldwide. By far, 270 protein-coding genes have been identified to cause IRD when defective. However, only one microRNA (miRNA), miR-204, has been reported to be responsible for IRD when a point-mutation occurs in its seed sequence. Previously, we identified that a conserved, polycistronic, paralogous miRNA cluster, the miR-183/96/182 cluster, is highly specifically expressed in all photoreceptors and other sensory organs; inactivation of this cluster in mice resulted in syndromic IRD with multi-sensory defects. We hypothesized that mutations in the miR-183/96/182 cluster in human cause IRD. To test this hypothesis, we perform mutation screening in the pre-miR-183, -96, -182 in >1000 peripheral blood DNA samples of patients with various forms of IRD. We identified six sequence variants, three in pre-miR-182 and three in pre-miR-96. These variants are in the pre-miRNA-182 or -96, but not in the mature miRNAs, and are unlikely to be the cause of the IRD in these patients. In spite of this, the nature and location of these sequence variants in the pre-miRNAs suggest that some may have impact on the biogenesis and maturation of miR-182 or miR-96 and potential roles in the susceptibility to diseases. Although reporting on negative results so far, our study established a system for mutation screening in the miR-183/96/182 cluster in human for a continued effort to unravel and provides deeper insight into the potential roles of miR-183/96/182 cluster in human diseases.

【 授权许可】

Unknown