Correlation between genotype and phenotype in primary open angle glaucoma of Brazilian families with mutations in exon 3 of the TIGR/MYOC gene

Arquivos Brasileiros de Oftalmologia

Cristine Araújo Povoa²  Roberto Freire Santiago Malta¹  Mariana De Moraes Rezende¹  Karla Fabiana Santana De Melo²  Daniel Giannella-neto² 

[1] ,Universidade de São Paulo Faculdade de Medicina São Paulo SP ,Brasil

关键词: Glaucoma;    open-angle;    Genes;    Phenotype;    Genotype;    Mutation;    Genetic screening;    Brazil;    Glaucoma de ângulo aberto;    Genes;    Fenótipo;    Genótipo;    Mutação;    Triagem genética;    Brasil;   

DOI  :  10.1590/S0004-27492006000300002

来源: SciELO

【 摘 要 】

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 a 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 ± 3.8mmHg 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 (p<0.0007) and vertical cup/disc ratio when compared to the patients without mutation (p<0.023). CONCLUSIONS: Cys433Arg mutation in exon 3 of the TIGR/MYOC gene is related to juvenile-onset POAG (J-POAG) in Brazilian families and autosomal dominant inheritance. The phenotype of this mutation is characterized by varied ages at diagnosis, causing J-POAG and late-onset POAG, associated with high IOP.

【 授权许可】

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