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Abstract #14456 Published in IGR 8-4
Correlation between genotype and phenotype in primary open angle glaucoma of Brazilian families with mutations in exon 3 of the TIGR/MYOC gene
Povoa CA; Santiago Malta RF; de Moraes Rezende M; Santana de Melo KF; Giannella Neto DArquivos Brasileiros de Oftalmologia 2006; 69: 289-297
PURPOSE: To investigate the phenotype of primary open-angle glaucoma (POAG) in Brazilian families with mutation in exon 3 of TIGR/MYOC. METHODS: Seventy-eight POAG patients with a positive family history and eighteen unrelated patients with POAG were screened by automated DNA sequencing for mutations in exon 3 of the TIGR/MYOC gene. The pedigrees of POAG patients with mutations that lead to amino acid change were built. All available relatives of the index cases were also examined and genotyped by sequencing. RESULTS: Four sequence variants were identified in exon 3 of the TIGR/ MYOC gene (Tyr347Tyr, Pro370Pro, Lys398Arg and Cys433Arg) from the 96 initially screened patients. The Lys398Arg mutation was previously described as polymorphism and in our study did not segregate with POAG. The most prevalent mutation was Cys433Arg, affecting 3 index cases (3.1% or 3/96). In two different families. 8/56 subjects presented Cys433Arg mutation and had POAG, 5/56 had ocular hypertension and 8/56 had no disease manifestation. POAG patients had a median age at diagnosis of 43.25 yr (17-58 yr) and intraocular pressure (IOP) with a mean of 36.3 ± 3.8 mmHg for the right eye and 37.6 ± 9.75 mmHg for the left eye. The group of patients with Cys433Arg mutation had significantly higher IOP and vertical cup/disc ratio when compared to the patients without mutation (p < 0.023). CONCLUSIONS: Cys433Arg mutation in exon 3 of the TI GR/MYOC gene is related to juvenile-onset POAG (J-POAG) in Brazilian families and autosomal dominant inheritance. The phenotype of this mutation is chracterized by varied ages at diagnosis, causing J-POAG and late-onset POAG, associated with high IOP.
Dr. C.A. Povoa, Rua 38, numero 296, Goiania, GO 74823-350, Brazil
Classification:
3.4.2 Gene studies (Part of: 3 Laboratory methods > 3.4 Molecular genetics)
