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Edward Ryan Collantes, Manuel Jr. Delfin, Ferdinand Atienza, Baojian Fan, Janey L Wiggs; A prospective study of the natural history of MYOC-associated juvenile open-angle glaucoma. Invest. Ophthalmol. Vis. Sci. 2021;62(8):1496.
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Juvenile open angle glaucoma (JOAG) can lead to irreversible blindness if not detected and treated at early stages of disease. Myocilin (MYOC) mutations are known to cause JOAG in individuals and families worldwide. We have identified a large Filipino family with JOAG due to a novel MYOC stop-loss mutation, c.1515A>G (p.*505Wext*42). Examining this family over 4 years has allowed for determining the natural history of disease related to this mutation, including information about the onset of intraocular pressure (IOP) elevation, timing of treatment and therapeutic outcomes.
Fifty-seven members of a 4-generation family were screened for the novel MYOC stop loss mutation. 26 family members carried the mutation and were recruited for the clinical study. Clinically unaffected mutation carriers were monitored over the course of 51 months including visual acuity (VA) assessment, slit-lamp exam, applanation tonometry, gonioscopy and fundus exam.
Twenty six of the 57 family members were carriers of the novel stop loss mutation. 13 mutation carriers were affected by JOAG (mean age of diagnosis 28.6 years; SD=7.9; range 16-43). Despite treatment, 11 mutation carriers had no light perception in at least one eye. Five mutation carriers were newly diagnosed with JOAG as part of the family ascertainment.Of the 26 mutation carriers, 8 subjects (mean age 7 years; SD=4.9; range 1-15) did not have clinical evidence of glaucoma. These 8 subjects were examined regularly over the course of 51 months. One subject developed IOP elevation at age 14. The average intraocular pressure was within the normal range for the remaining 7 subjects (range: 12-20 mmHg). There was no significant change in the VA and cup to disc ratio and no indication of an upward IOP trend in this subgroup.
This is the first stop-loss MYOC mutation that has been described. In this family, this mutation appears to exhibit variable age of onset with 100% penetrance by age 49. It does not seem to cause elevated IOP in the first decade of life. Similar to a common MYOC mutation (GLN368X), the variable age of onset could suggest that other factors, including POAG polygenic risk score can modify disease development. Evaluation of unaffected mutation carriers provides insight into the natural history of MYOC-associated JOAG. This information will be of critical importance as gene-based therapies become available in the future.
This is a 2021 ARVO Annual Meeting abstract.
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