The goal of this project is to identify novel genes involved in human retinal disorders, a stated priority of the National Eye Institute. To accomplish this, additional genes whose mutations cause Retinitis Pigmentosa (RP), one of the most common forms of inherited retinal degeneration that affects an estimated 100,000 people in the United States alone, will be identified by combining whole exome sequencing with genetic mapping. Mutations in known RP genes account for about 50% of all cases in the European population, suggesting that many additional RP genes remain to be identified. To identify additional RP disease genes, we have collected more than 500 patient families with autosomal recessive RP (arRP) from around the world. Screen for mutations in known arRP disease genes suggests that about 300 of these families are likely to carry mutations in novel RP disease genes. Therefore, this collection represents a well characterized, rich resource for identifying new genes that can cause RP. In this proposal, we will identify the underlying mutations in these patients using a combination of whole exome sequencing, bioinformatics, statistics, and functional studies.
Our Specific Aims are to: 1. Whole exome sequencing of RP families to identify novel RP disease genes 2. Confirmation and discovery of novel RP genes by screening a 1300-patient cohort 3. Phenotype genotype analysis of RP families and continued enrollment Discovery of novel RP genes will assist the development of new diagnostic tools and treatments. In addition, since mutations in RP disease genes also cause other retinal dystrophies, isolation of additional RP disease genes will provide important insights into the molecular mechanisms underlying both RP and retinal dystrophies in general.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
Project #
Application #
Study Section
Genetics of Health and Disease Study Section (GHD)
Program Officer
Shen, Grace L
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Baylor College of Medicine
Schools of Medicine
United States
Zip Code
Soens, Zachry T; Li, Yuanyuan; Zhao, Li et al. (2016) Hypomorphic mutations identified in the candidate Leber congenital amaurosis gene CLUAP1. Genet Med 18:1044-51
Tajiguli, Abulikemu; Xu, Mingchu; Fu, Qing et al. (2016) Next-generation sequencing-based molecular diagnosis of 12 inherited retinal disease probands of Uyghur ethnicity. Sci Rep 6:21384
Xu, Mingchu; Eblimit, Aiden; Wang, Jing et al. (2016) ADIPOR1 Is Mutated in Syndromic Retinitis Pigmentosa. Hum Mutat 37:246-9
Coppieters, Frauke; Ascari, Giulia; Dannhausen, Katharina et al. (2016) Isolated and Syndromic Retinal Dystrophy Caused by Biallelic Mutations in RCBTB1, a Gene Implicated in Ubiquitination. Am J Hum Genet 99:470-80
Arno, Gavin; Agrawal, Smriti A; Eblimit, Aiden et al. (2016) Mutations in REEP6 Cause Autosomal-Recessive Retinitis Pigmentosa. Am J Hum Genet 99:1305-1315
Zhao, Li; Chen, Yiyun; Bajaj, Amol Onkar et al. (2016) Integrative subcellular proteomic analysis allows accurate prediction of human disease-causing genes. Genome Res 26:660-9
Zhang, Qi; Xu, Mingchu; Verriotto, Jennifer D et al. (2016) Next-generation sequencing-based molecular diagnosis of 35 Hispanic retinitis pigmentosa probands. Sci Rep 6:32792
Xu, Mingchu; Yamada, Takeyuki; Sun, Zixi et al. (2016) Mutations in POMGNT1 cause non-syndromic retinitis pigmentosa. Hum Mol Genet 25:1479-88
Astuti, Galuh D N; Sun, Vincent; Bauwens, Miriam et al. (2015) Novel insights into the molecular pathogenesis of CYP4V2-associated Bietti's retinal dystrophy. Mol Genet Genomic Med 3:14-29
Kmoch, S; Majewski, J; Ramamurthy, V et al. (2015) Mutations in PNPLA6 are linked to photoreceptor degeneration and various forms of childhood blindness. Nat Commun 6:5614

Showing the most recent 10 out of 25 publications