Abstract
Abstract
Purpose : To investigate the frequency of myocilin (MYOC) mutations in patients diagnosed with Primary Open Angle Glaucoma (POAG) from a West Yorkshire clinic.
Methods : Patients were diagnosed with POAG by an experienced ophthalmologist. Genomic DNA was extracted from peripheral blood. PCR and direct Sanger Sequencing was used to analyse the coding exons and splice recognition sites of the MYOC gene. The frequency of the variants in the general population was investigated using the gnomAD database and their pathogenicity assessed using prediction programs PolyPhen2, SIFT, PROVEAN, CADD, BLOSUM62, MutationTaster and Human Splicing Finder.
Results : 12 out of 219 patients (5%) analysed had a MYOC mutation that was predicted to be pathogenic and could possibly account for their disease phenotype. The patients between them had 8 MYOC mutations including a novel frameshift (p.Lys484Argfs), previously identified nonsense (p.Gln368Stop) and non-synonymous (p.Glu352Lys, p.Lys398Arg and p.Thr419Ala) mutations as well as synonymous variants (p.Thr204Thr, p.Thr285Thr and p.Glu396Glu) that are predicted to affect splicing.
Conclusions : MYOC mutations are likely to account for 5% of the POAG cohort studied, which is consistent with findings in previously published studies. This leaves an enriched cohort of cases for systematic screening of the other known genes that cause POAG.
Purpose : To investigate the frequency of myocilin (MYOC) mutations in patients diagnosed with Primary Open Angle Glaucoma (POAG) from a West Yorkshire clinic.
Methods : Patients were diagnosed with POAG by an experienced ophthalmologist. Genomic DNA was extracted from peripheral blood. PCR and direct Sanger Sequencing was used to analyse the coding exons and splice recognition sites of the MYOC gene. The frequency of the variants in the general population was investigated using the gnomAD database and their pathogenicity assessed using prediction programs PolyPhen2, SIFT, PROVEAN, CADD, BLOSUM62, MutationTaster and Human Splicing Finder.
Results : 12 out of 219 patients (5%) analysed had a MYOC mutation that was predicted to be pathogenic and could possibly account for their disease phenotype. The patients between them had 8 MYOC mutations including a novel frameshift (p.Lys484Argfs), previously identified nonsense (p.Gln368Stop) and non-synonymous (p.Glu352Lys, p.Lys398Arg and p.Thr419Ala) mutations as well as synonymous variants (p.Thr204Thr, p.Thr285Thr and p.Glu396Glu) that are predicted to affect splicing.
Conclusions : MYOC mutations are likely to account for 5% of the POAG cohort studied, which is consistent with findings in previously published studies. This leaves an enriched cohort of cases for systematic screening of the other known genes that cause POAG.
| Original language | English |
|---|---|
| Pages | 1502-1502 |
| Number of pages | 1 |
| Publication status | Published - Jun 2021 |