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R. A. Perez-Grossmann, M. L. Guevara-Fujita, A. Estrada-Cuzcano, H. Pawar, J. E. Richards, R. Fujita; Recurrent Myocilin Asn480Lys Glaucoma Causative Mutation Arises de novo in a Family of Andean Descent. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5591.
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To identify and characterise MYOC mutations in a group of 11 Primary Open Angle Glaucoma (POAG) families of South American native and admixed origins from Peru.
Patients and relatives participated voluntarily after signing informed consent. Ophthalmic examination included open anterior-chamber angles, presence of glaucomatous optic disc changes, slit lamp, gonioscopy, intraocular pressure and pachymetry. DNA was obtained from 5 ml of peripheral blood, MYOC exons were amplified and analysed under "conformational sensitive gel electrophoresis" (CSGE) and sequenced to detect and identify mutations.
Two mutations were found. In a family of admixed Andean, Caucasian and probably African descent, a common known polymorphism MYOC Arg76Lys (R76K) cosegregated with POAG in 6 out of the 7 POAG patients but also present in 6 normal relatives. Another family of native Andean descent presented a MYOC mutation Asn480Lys (N480K), previously reported to be causative in two unrelated French and Dutch familiar groups with glaucoma of variable expressivity (nucleotide 1440 C→A). The Peruvian N480K mutation is caused by a different transversion (nucleotide 1440 C→G), revealing a third, independent event. N480K is the mutation reported in the highest number of POAG patients (> 90 cases) and has been proposed as a model to study a common mutation with variable phenotypic presentation to study other modulating environmental and genetic factors for expressivity.
A screening of MYOC mutations of 11 POAG families revealed an independent nucleotide mutation 1440 C→G in an Andean family that lead to N480K aminoacid change, the most common causal mutation reported for POAG. Follow-up of the evolution of POAG in this Andean family and comparison with European N480K, will contribute to the information about disease manifestation, progression and treatment response in the context of a distinct ethnic background as well as climatic, altitude and socioeconomical conditions.
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