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Exome-based investigation of the genetic basis of human pigmentary glaucoma
- Source :
- BMC Genomics, BMC Genomics, Vol 22, Iss 1, Pp 1-12 (2021)
- Publication Year :
- 2021
-
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.
- Subjects :
- Glaucoma
Iris
Biology
QH426-470
Exomes
03 medical and health sciences
Mice
0302 clinical medicine
Human genetics
Exome Sequencing
medicine
Genetics
Animals
Humans
Exome
TYRP1
Gene
Exome sequencing
Pigmentary Glaucoma
0303 health sciences
Membrane Glycoproteins
Pigmentation
Research
030305 genetics & heredity
food and beverages
medicine.disease
PMEL
Pigment dispersion syndrome
030221 ophthalmology & optometry
TP248.13-248.65
Glaucoma, Open-Angle
Biotechnology
Subjects
Details
- ISSN :
- 14712164
- Volume :
- 22
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- BMC genomics
- Accession number :
- edsair.doi.dedup.....ef7cbfac7f7a31c398900472c31bce67