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E. Milla, S. Duch, M. Carballo, I. Hernan, E. Planas, O. Buchacra, M. Gamundi; Genetic Screening: A Diagnostic Tool for Familial Glaucoma and Ocular Hypertensive Patients. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3118. doi: https://doi.org/.
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.Glaucoma is the second most prevalent cause of blindness worldwide, projected to affect more than 60 million people by 2010. The purpose of this study was identification of myocilin (MYOC) and CYP1B1 mutationsin a Spanish population affected by different clinical forms of familial glaucoma or ocular hypertension (OHT) in order to better determine our therapeutic approach.
thorough ophthalmologic examination that included pachymetry-corrected intraocular pressure applanation tonometry and optical coherence tomography or Heidelberg retinal tomography. Mutation detection was performed in DNA isolated from patients' peripheral blood. Direct genomic sequencing was used to evaluate the coding sequences of MYOC and CYP1B1 genes in patients affected with glaucoma.
We recruited 95 individuals from 58 families (61 index patients) with a positive family history of glaucoma. We identified three known MYOC mutations in exon 3 and one novel MYOC mutation in exon 2: a Gln368stop mutation in a family with severe adult onset primary open angle glaucoma (POAG); a Val426Phe mutation in a family with moderate juvenile open angle glaucoma (JOAG); Ala427Thr in a low-tension glaucoma case and a Glu218Lys (novel) in a POAG family. We identified the following single nucleotide polymorphisms (SNPs) in MYOC : Thr285Thr in a primary congenital glaucoma (PCG) patient; Gly122Gly in a low-tension glaucoma; Val426Val (novel) in a non treated OHT patient and eight patients with Tyr347Tyr of which 2 were JOAG, 2 primary closed angle glaucomas, 2 low-tension glaucomas, 1 non treated OHT patient and 1 PCG. CYP1B1 mutations were found in six unrelated patients either in the homozygous or heterozygous state. Five novel mutations were identified namely Val432Leu; Asn453Ser; 1064-1076 del; Val432Leu and 1198-1209 dup. One patient presented with a concomitant MYOC polymorphism.
the Gln368stop mutation caused irreversible blindness in our patients contrarily with the expected mild phenotype normaly described in the literature; the presence or absence of both MYOC mutations and polymorphisms strongly influenced our therapeutic attitude in order to prescribe or withdraw hypotensive drugs or other type of treatments. The genetic analysis helped us to provide a more accurate visual prognosis as well as a genetic counselling. This amount of information contributed to diminish the anxiety of the patients and their relatives.
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