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Abstract #91259 Published in IGR 21-4
Prevalence of MYOC risk variants for glaucoma in different populations
Liuska PJ; Harju M; Kivelä TT; Turunen JAActa Ophthalmologica 2021; 99: e1090-e1097
PURPOSE: To assess the clinical relevance of myocilin (MYOC) gene variants as risk factors for glaucoma in literature and to estimate their prevalence in different populations. METHODS: We reviewed the literature for published MYOC variants in glaucoma patients and estimated their prevalence in general population using gnomAD and BRAVO databases. We used several bioinformatics tools and the criteria of the American College of Medical Genetics and Genomics (ACMG) to assess the pathogenicity of the variants. We evaluated the carrier frequency of the variants in gnomAD, including its subpopulations. RESULTS: We found 13 missense and 5 loss-of-function (LOF) reported variants in MYOC that were both probable pathogenic or risk variants and listed in gnomAD. Six likely pathogenic missense variants were p.(Cys25Arg), p.(Gln48His), p.(Gly326Ser), p.(Thr353Ile), p.(Thr377Met) and p.(Gly399Val). They were most prevalent in East and South Asia (frequency, 0.92% and 0.81%, respectively). The most common missense variants were p.(Thr353Ile) (0.91% in East Asia) and p.(Gln48His) (0.79% in South Asia). Five LOF variants were p.(Arg46Ter), p.(Arg91Ter), p.(Arg272Ter), p.(Gln368Ter) and p.(Tyr453MetfsTer11). We considered these glaucoma risk variants. They were most prevalent in the East Asian and the Finnish population (0.93% and 0.33%, respectively). CONCLUSION: Pathogenic MYOC variants appear to be population-associated. Our results highlight allelic heterogeneity of MYOC variants in open-angle glaucoma. Many of the probable pathogenic variants are over-represented in some of the populations causing doubt of their status as monogenic disease-causing variants.
Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland.
Full articleClassification:
3.4.2 Gene studies (Part of: 3 Laboratory methods > 3.4 Molecular genetics)
