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Abstract #94296 Published in IGR 22-2
Biallelic variants in are associated with primary open-angle glaucoma and primary angle-closure glaucoma
Li X; Sun W; Xiao X; Fang L; Li S; Liu X; Zhang QBritish Journal of Ophthalmology 2022; 106: 1710-1715
BACKGROUND/AIMS: This study aims to assess the contribution of biallelic variants in patients with different forms of glaucoma, especially primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG), based on a systematic analysis of exome sequencing (ES). METHODS: Potentially pathogenic variants were selected from the ES data of 5307 subjects with various eye conditions through multiple bioinformatics analyses. Of the 5307 subjects, 1221 probands had different forms of primary glaucoma. The genotype-phenotype correlation was assessed by a systematic review of biallelic variants that including our data and data from the literature. The expression profile of in human tissues was determined at the mRNA and protein levels. RESULTS: Biallelic variants, including one frameshift and six missense variants, were exclusively present and significantly enriched in patients with glaucoma (one with juvenile open-angle glaucoma (JOAG), two with POAG and two with PACG) compared with none of the 4086 probands with other eye conditions in this cohort (p=4.1E-07). The effect of variants in these patients is relatively mild compared with that reported in patients with anterior segment dysgenesis or primary congenital glaucoma. mRNA was highly expressed in the optic nerve, ciliary body, retina and iris, whereas the CPAMD8 protein was mainly detected in the nonpigmented epithelium of the iris and ciliary process, determined by immunohistochemistry. CONCLUSIONS: The data from this study not only provide further evidence to support the association of biallelic variants with JOAG but also suggest that biallelic variants might be associated with POAG and PACG.
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, China.
Full articleClassification:
3.4.2 Gene studies (Part of: 3 Laboratory methods > 3.4 Molecular genetics)
9.3.2 Chronic primary angle closure glaucoma (pupillary block) (Part of: 9 Clinical forms of glaucomas > 9.3 Primary angle closure glaucomas)
