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Joanna Swierkowska, Justyna A Karolak, Malgorzata Rydzanicz, Agata Frajdenberg, Malgorzata Mrugacz, Monika Podfigurna-Musielak, Sangeetha Vishweswaraiah, Uppala Radhakrishna, Marzena Gajecka; Further clinical, genetic and epigenetic evidence of multifaceted high myopia etiology in Polish patients. Invest. Ophthalmol. Vis. Sci. 2020;61(7):2674.
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© ARVO (1962-2015); The Authors (2016-present)
High myopia (HM) is an eye disorder characterized by a refractive error greater than -6.0 dioptres and axial length (AL) more than 26.0 mm. While the involvement of genetic factors in HM etiology has been discussed in the literature, no general conclusions about genetic basis of HM has been made so far. To date, we identified three novel loci for HM in Polish families (PMID:21850178), showed no association between previously published candidate genes and HM in Polish subjects (PMID:21976954), and identified novel missense variants, c.1642G>C in FLRT3 and c.938C>T in SLC35E2B in familial HM. Recently, we conducted the genome-wide methylation study in Polish children with HM and matched controls (PMID:30858441). Here we present further experimental analyses indicating the complexity of HM’s genetic background.
We performed additional analyses of exome sequencing data obtained from 17 members of seven unrelated Polish HM families and a validation by Sanger sequencing and segregation analyses in other family members. Moreover, the statistical assessment of clinical data and validation of chosen, based on the literature data, sequence variants influencing the value of AL, intraocular pressure (IOP), and corneal curvature (CC) were performed in four Polish HM families. Furthermore, based on the genome-wide methylation results, we performed molecular pathways overrepresentation analyses using the ConsensusPathDB.
Further evaluation of exome sequencing results revealed segregation of c.3704G>A in ABCC6 with familial HM. The assessed sequence variants did not contribute to AL, IOP, CC in Polish HM subjects. Hypermethylated CpG dinucleotides in promoter regions of genes GSTM1, PPP1R18, TRAPPC11, XRCC2, OXA1L, FARP2, and hypomethylated in genes ABHD13, SORBS2, SLC25A3P1, TANC1, ATXN1, and several overrepresented pathways related to myopia were identified.
Results suggest that ABCC6 variant might contribute to HM in Polish family, but other than analyzed sequence variants contribute to AL, IOP, and CC in the studied families. Identified hyper- and hypomethylated genes could influence gene expression and take part in HM pathogenesis in Polish children. Our results further indicate the complexity of genetic background of HM in Polish subjects.
This is a 2020 ARVO Annual Meeting abstract.
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