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C. Povoa, R.F. Malta, M.M. Rezende, D. Giannella-Neto; Correlation between Genotype and Phenotype in Open Angle Glaucoma Brazilians' Families with Mutations in the Exon-3 of TIGR/MYOC Gene . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1105.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:To investigate the phenotype of POAG in families with mutation in the exon 3 of TIGR/MYOC. Methods: Seventy eight (81.2%) patients with positive family history of POAG and eighteen (18.7%) patients with POAG were screened by automated DNA sequencing for mutations in the exon 3 of TIGR/MYOC. The genealogical trees from the index cases carrying not silent mutation was build. All members of their pedigree were examined for signs of glaucoma and the presence of mutations was ascertained by direct automated sequencing. The patients' phenotype with and without mutation were analysed and compared by Mann-Withney statistical test.Results: Four sequence variations were identified in the exon 3 of TIGR/MYOC gene (CYS433ARG, LYS398ARG, PRO370PRO and TYR347TYR) from the 96 patients initially screened. The most prevalent mutation was CYS433ARG, affecting 3.1% of the subjects. The frequency of this mutation in patients with POAG and positive family history was 5.2%. Eight individuals from two differents families carried CYS433ARG mutation and had POAG. The mean age at diagnosis was 45 years, and median of age at diagnostic 43.25 years (ranging from 17-63 years), high intraocular pressure (IOP) with mean of 36.3 ± 3.8 mmHg for right eye and 37.6 ± 9.75 mmHg for left eye and anterior chamber without goniodysgenesis. Seven ocular hypertension (OHT) were identified, five of them with CYS433ARG mutation (their mean age at diagnosis was about eleven years less than the patients carrying mutation and POAG) had initial IOP mean of 22.8 mmHg for the right eye and 21.8 mmHg for left eye. Eight individuals with no GPAA or HO subjects with mean age at diagnostic of 19 years, median of 14.5 years and IOP mean of 13.3 mmHg for right eye and 13.7 mmHg for left eye. The group of patients with CYS433ARG mutation had significantly higher IOP (p<0.0007) and vertical cup/disc than the without ones (p<0.023). A third family carrying LYS398ARG mutation/polimorfism was evaluated but the mutation did not cosegregate with the POAG. Conclusions: In conclusion, CYS433ARG mutation in exon 3 of TIGR/MYOC gene is related with J-OAG brasilians' families and autossomal dominant inheritance. The phenotype of this mutation is characterized by different ages of diagnosis, causing J-GPAA and late-onset POAG, high and uncontrolled IOP.
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