Journal article
Exome-based investigation of the genetic basis of human pigmentary glaucoma
BMC genomics, Vol.22(1), pp.477-477
06/26/2021
DOI: 10.1186/s12864-021-07782-0
PMCID: PMC8235805
PMID: 34174832
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.
Details
- Title: Subtitle
- Exome-based investigation of the genetic basis of human pigmentary glaucoma
- Creators
- Carly van der Heide - 375 Newton Road, Iowa City, IA52245 USAWes Goar - 375 Newton Road, Iowa City, IA52245 USAKacie J Meyer - Iowa City, IA USAWallace L. M Alward - 375 Newton Road, Iowa City, IA52245 USAErin A Boese - 375 Newton Road, Iowa City, IA52245 USANathan C Sears - 375 Newton Road, Iowa City, IA52245 USABen R Roos - 375 Newton Road, Iowa City, IA52245 USAYoung H Kwon - 375 Newton Road, Iowa City, IA52245 USAAdam P DeLuca - 375 Newton Road, Iowa City, IA52245 USAOwen M Siggs - Adelaide, South Australia AustraliaClaudia Gonzaga-Jauregui - Tarrytown, NY USAVal C Sheffield - 375 Newton Road, Iowa City, IA52245 USAKai Wang - Iowa City, IA USAEdwin M Stone - 375 Newton Road, Iowa City, IA52245 USARobert F Mullins - 375 Newton Road, Iowa City, IA52245 USAMichael G Anderson - 375 Newton Road, Iowa City, IA52245 USABao Jian Fan - Boston, MA USARobert Ritch - New York, NY USAJamie E Craig - Adelaide, South Australia AustraliaJaney L Wiggs - Boston, MA USATodd E Scheetz - 375 Newton Road, Iowa City, IA52245 USAJohn H Fingert - 375 Newton Road, Iowa City, IA52245 USA
- Resource Type
- Journal article
- Publication Details
- BMC genomics, Vol.22(1), pp.477-477
- DOI
- 10.1186/s12864-021-07782-0
- PMID
- 34174832
- PMCID
- PMC8235805
- NLM abbreviation
- BMC Genomics
- ISSN
- 1471-2164
- eISSN
- 1471-2164
- Publisher
- BioMed Central
- Language
- English
- Date published
- 06/26/2021
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Electrical and Computer Engineering; Molecular Physiology and Biophysics; Psychiatry; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Biostatistics; Medical Genetics and Genomics; Center for Bioinformatics and Computational Biology; Ophthalmology and Visual Sciences
- Record Identifier
- 9984095015002771
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