Exome-based investigation of the genetic basis of human pigmentary glaucoma

BMC Genomics

Young H. Kwon¹  Wallace L. M. Alward¹  Adam P. DeLuca¹  Todd E. Scheetz¹  Edwin M. Stone¹  Ben R. Roos¹  Robert F. Mullins¹  Wes Goar¹  John H. Fingert¹  Michael G. Anderson¹  Erin A. Boese¹  Val C. Sheffield¹  Carly van der Heide¹  Nathan C. Sears¹  Jamie E. Craig²  Owen M. Siggs²  Bao Jian Fan³  Janey L. Wiggs³  Robert Ritch⁴  Kai Wang⁵  Kacie J. Meyer⁵  Claudia Gonzaga-Jauregui⁶ 

[1] Department of Ophthalmology and Visual Sciences, Carver College of Medicine, 3111B Medical Education and Research Facility, University of Iowa;Department of Ophthalmology, Flinders Medical Centre;Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Boston;Einhorn Research Center, New York Eye and Ear Infirmary of Mount Sinai;Institute for Vision Research, University of Iowa;Regeneron Genetics Center, Regeneron Pharmaceuticals Inc.;

关键词: Pigmentary Glaucoma;    Pigment dispersion syndrome;    Glaucoma;    Exomes;    Human genetics;   

DOI  :  10.1186/s12864-021-07782-0

来源: DOAJ

【 摘 要 】

Abstract Background Glaucoma is a leading cause of visual disability and blindness. Release of iris pigment within the eye, pigment dispersion syndrome (PDS), can lead to one type of glaucoma known as pigmentary glaucoma. PDS has a genetic component, however, the genes involved with this condition are largely unknown. We sought to discover genes that cause PDS by testing cohorts of patients and controls for mutations using a tiered analysis of exome data. Results Our primary analysis evaluated melanosome-related genes that cause dispersion of iris pigment in mice (TYRP1, GPNMB, LYST, DCT, and MITF). We identified rare mutations, but they were not statistically enriched in PDS patients. Our secondary analyses examined PMEL (previously linked with PDS), MRAP, and 19 other genes. Four MRAP mutations were identified in PDS cases but not in controls (p = 0.016). Immunohistochemical analysis of human donor eyes revealed abundant MRAP protein in the iris, the source of pigment in PDS. However, analysis of MRAP in additional cohorts (415 cases and 1645 controls) did not support an association with PDS. We also did not confirm a link between PMEL and PDS in our cohorts due to lack of reported mutations and similar frequency of the variants in PDS patients as in control subjects. Conclusions We did not detect a statistical enrichment of mutations in melanosome-related genes in human PDS patients and we found conflicting data about the likely pathogenicity of MRAP mutations. PDS may have a complex genetic basis that is not easily unraveled with exome analyses.

【 授权许可】

Unknown