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A Journal on Ophthalmology




Minerva Oftalmologica 2002 June;44(2):61-70

language: Italian

Primary open-angle glaucoma genetics: phenotype variability in the most common mutation of the Miocylin gene

Angius A.


Primary open-angle glaucoma is the highly prevalent cause of irreversible blindness in industrialized countries. This pathology may be classified according to the age of onset in an adult form, diagnosed in patients over 40, and juvenile form occurring earlier than 40. The first locus, GLC1A, associated to the disease has been mapped on chromosome 1q23-q25. The gene associated with GLC1A was identified and found to code for a protein named Miocylin. A large number of mutations were identified in populations of various ethnic groups covering 3% of cases in the general population. Most common mutations are: Gly364Val, Gln368stop, Thr377Met, 386ins397, Tyr437His and Ile477Asn. The large part of them caused a severe juvenile phenotype with high intraocular pressure values and high disease penetrance. The most common mutation is Gln368stop. Molecular analysis of 4 different ethnic groups reveals a common founder effect. Clinical phenotype of Gln368Stop patients is well controlled by medical therapy and causes blindness only in old age. Phenotypical differences of Gln368stop patients were probably due to slow and progressive mechanism caused by the different protein structure that may be rapidly eliminated producing a lower production of normal protein. Gln368stop mutation and advance age were securely two important risk factors. Therefore, the large number of unaffected and affected carriers in the same age groups indicates that additional genetic and/or non genetic factors are involved in the development of the disease.

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