Mutações no gene MYOC/TIGR em urna população brasileira com glaucoma juvenil e glaucoma primário de ângulo aberto

Vasconcellos, José Paulo Cabral de; Melo, Monica B.; Menezes, Fernando; Tsukumo, Daniela Miti Lemos; Costa, Vital Paulino; Kara-José, Newton; Costa, Fernando F.

doi:10.5935/0004-2749.19980013

RESUMO

Objetivo:

Avaliar a freqüência e o tipo de mutação no gene “trabecular meshwork-induced glucocorticoid response protein” (MYOC/TIGR) entre pacientes com glaucoma primário de ângulo aberto (GPAA) e glaucoma juvenil de ângulo aberto (GJAA).

Métodos:

DNA genômico foi extraído a partir de sangue periférico de pacientes com GPAA e GJAA. Posteriormente foram realizados PCR e SSCP para identificar possíveis mutações no gene MYOC/TIGR, os quais foram confirmados por meio de análise por sequenciamento.

Resultados:

Foram estudados dezenove pacientes com GJAA. Oito pacientes (42%) apresentaram uma mutação de ponto no codon 433 (exon 3), ocasionando a substituição de uma cisteína (TGT) por uma arginina (CGT). Entre os pacientes com GPAA (n = 52), foram encontrados dois (3,8%) com mutação no gene MYOC/TIGR. Um deles mostrou uma mutação de ponto no aminoácido 368, substituindo uma glutamina por um codon de terminação e o outro paciente apresentou a mesma mutação observada nos pacientes com GJAA.

Conclusão:

Identifícou-se uma nova mutação no gene MYOC/ TIGR em pacientes brasileiros com GPAA e GJAA. A ocorrência de mutações no gene MYOC/TIGR em 42% dos pacientes com GJAA assim como em 3,8% dos pacientes com GPAA poderia ser maior, uma vez que o gene não foi estudado em sua totalidade (apenas 400 pb do exon 3).

Palavras-chave:
Glaucoma juvenil; Glaucoma primário de ângulo aberto; Gene MYOC; Gene TIGR

SUMMARY

Purpose:

To evaluate the frequency and type of mutation in the trabecular meshwork-induced glucocorticoid response protein (MYOC/TIGR) gene among Brazilian patients with juvenile open angle glaucoma (JOAG) and primary open angle glaucoma (POAG).

Methods:

The genomic DNA of consecutive patients with POAG and JO AG was extracted from peripheral blood. Subsequently, PCR and SSCP were performed to identify possible mutations in the MYOC/TIGR gene, which were confirmed by sequencing analysis.

Results:

Nineteen patients with JOAG were studied. Eight patients (42%) showed a single mutation in exon 3 at amino acid 433, which codifies an arginine (CGT) instead of a cysteine (TGT). Among patients with POAG (n = 52), we found two (3.8%) with a mutation in the MYOC/TIGR gene. One of them showed a point mutation at amino acid 368, codifying a stop codon instead of a glutamine. The other patient had the same mutation as those observed in JOAG patients.

Conclusion:

A new mutation in the MYOC/TIGR gene in Brazilian patients with JOAG and POAG was reported. The ocurrence of mutations in the MYOC/TIGR gene in 42% of Brazilian patients with JOAG as well as in 3.8% of those with POAG could be even higher, since the full gene was not evaluated (only 400 bp of exon 3).

Keywords:
Juvenile glaucoma; Primary open angle glaucoma; MYOC gene; TIGR gene

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REFERENCIAS

¹
Dickens CJ, Hoskins HD. Epidemiology and pathophysiology of congenital glaucoma. Kathryn H. Falk, ed. The Glaucomas (Clinical Science). St. Louis, Mosby-Year Book, 1996:729-38.
²
Johnson AT, Drack AY, Kwitek AE et al. Clinical features and linkage analysis of a family with autosomal dominant juvenile glaucoma. Ophthalmology 1993;100:525-9.
³
Sheffield VC, Stone EM, Alward WLM et al. Genetic linkage of familial open angle glaucoma to chromosome Iq21-q31. Nat Genet 1993;4:47-50.
⁴
Richards JE, Lichter PR, Boehnke M et al. Mapping of a gene for autosomal dominant juvenile-onset open-angle glaucoma to chromosome Iq. Am J Hum Genet 1994;54:62-70.
⁵
Wiggs JL, Haines JL, Paglinauan C et al. Genetic linkage of autosomal dominant juvenile glaucoma to Iq21-q31 in three affected pedigrees. Genomics 1994;21:299-303.
⁶
Wiggs JL, Del Bono EA, Schuman JS et al. Clinical features of five pedigrees genetically linked to the juvenile glaucoma locus on chromosome Iq21-q31. Ophthalmology 1995;102:1782-9.
⁷
Morissette J, Côté G, Anctil JL et al. A common gene for juvenile and adult-onset primary open-angle glaucomas confined on chromosome Iq. Am J Hum Genet 1995;56:1431-42.
⁸
Johnson AT, Richards JE, Boehnke M et al. Clinical phenotype of juvenile-onset primary open-angle glaucoma linked to chromosome Iq. Ophthalmology 1996;103:808-14.
⁹
Stone EM, Fingert JH, Alward WLM et al. Identification of a gene that causes primary open angle glaucoma. Science 1997;275:668-70.
¹⁰
Stoilova D, Child A, Trifan OC et al. Localization of a locus (GLCIB) for adult-onset primary open angle glaucoma to the 2cen-ql3 region. Genomics 1996;36:142-50.
¹¹
Wirtz MK, Samples JR, Kramer PL et al. Mapping a gene for adult-onset primary open angle glaucoma to chromosome 3q. Am J Hum Genet 1997;60:296-304.
¹²
Polansky JR, Fauss DJ, Chen P et al. Cellular pharmacology and molecular biology of the trabecular meshwork inducible glucocorticoid response gene product. Ophthalmologica 1997;211:126-39.
¹³
Saiki SK, Gelfand DH, Stoffel S et al. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 1988;239:487-91.
¹⁴
Orita M, Iwahana H, Kanazawa H et al. Detection of polymorphisms of human DNA by gel electrophoresis as single-strand conformation polymorphisms. Proc Natl Acad Sci USA 1989;86:2766-70.
¹⁵
Sarfarazi M. Recent advances in molecular genetics of glaucomas. Hum Mol Genet 1997;6:1667-77.
¹⁶
Richards JE, Lichter PR, Herman S et al. Probable exclusion of GLCIA as a candidate glaucoma gene in a family with middle age-onset primary open angle glaucoma. Ophthalmology 1996;103:1035-40.
¹⁷
Avramopoulos D, Kitsos G, Economou-Petersen E et al. Exclusion of one pedigree affected by adult onset primary open angle glaucoma from linkage to the juvenile glaucoma locus on chromosome 1q21-q31. J Mol Genet 1996;33:1043-4.
¹⁸
Adam MF, Belmouden A, Binisti P et al. Recurrent mutations in a single exon encoding the evolutionary conserved olfactomedin-homology domain of MYOC/TIGR in familial open-angle glaucoma. Hum Mol Genet 1997;6:2091-7.
¹⁹
Polansky JR, Fauss DJ, Chen P et al. Cellular pharmacology and molecular biology of the trabecular meshwork inducible glucocorticoid response gene product. Ophthalmologica 1997;211:126-39.

Datas de Publicação

Publicação nesta coleção
Dez 1998

Este é um artigo publicado em acesso aberto (Open Access) sob a licença Creative Commons Attribution, que permite uso, distribuição e reprodução em qualquer meio, sem restrições desde que o trabalho original seja corretamente citado.

[1] ¹
Dickens CJ, Hoskins HD. Epidemiology and pathophysiology of congenital glaucoma. Kathryn H. Falk, ed. The Glaucomas (Clinical Science). St. Louis, Mosby-Year Book, 1996:729-38.

[2] ²
Johnson AT, Drack AY, Kwitek AE et al. Clinical features and linkage analysis of a family with autosomal dominant juvenile glaucoma. Ophthalmology 1993;100:525-9.

[3] ³
Sheffield VC, Stone EM, Alward WLM et al. Genetic linkage of familial open angle glaucoma to chromosome Iq21-q31. Nat Genet 1993;4:47-50.

[4] ⁴
Richards JE, Lichter PR, Boehnke M et al. Mapping of a gene for autosomal dominant juvenile-onset open-angle glaucoma to chromosome Iq. Am J Hum Genet 1994;54:62-70.

[5] ⁵
Wiggs JL, Haines JL, Paglinauan C et al. Genetic linkage of autosomal dominant juvenile glaucoma to Iq21-q31 in three affected pedigrees. Genomics 1994;21:299-303.

[6] ⁶
Wiggs JL, Del Bono EA, Schuman JS et al. Clinical features of five pedigrees genetically linked to the juvenile glaucoma locus on chromosome Iq21-q31. Ophthalmology 1995;102:1782-9.

[7] ⁷
Morissette J, Côté G, Anctil JL et al. A common gene for juvenile and adult-onset primary open-angle glaucomas confined on chromosome Iq. Am J Hum Genet 1995;56:1431-42.

[8] ⁸
Johnson AT, Richards JE, Boehnke M et al. Clinical phenotype of juvenile-onset primary open-angle glaucoma linked to chromosome Iq. Ophthalmology 1996;103:808-14.

[9] ⁹
Stone EM, Fingert JH, Alward WLM et al. Identification of a gene that causes primary open angle glaucoma. Science 1997;275:668-70.

[10] ¹⁰
Stoilova D, Child A, Trifan OC et al. Localization of a locus (GLCIB) for adult-onset primary open angle glaucoma to the 2cen-ql3 region. Genomics 1996;36:142-50.

[11] ¹¹
Wirtz MK, Samples JR, Kramer PL et al. Mapping a gene for adult-onset primary open angle glaucoma to chromosome 3q. Am J Hum Genet 1997;60:296-304.

[12] ¹²
Polansky JR, Fauss DJ, Chen P et al. Cellular pharmacology and molecular biology of the trabecular meshwork inducible glucocorticoid response gene product. Ophthalmologica 1997;211:126-39.

[13] ¹³
Saiki SK, Gelfand DH, Stoffel S et al. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 1988;239:487-91.

[14] ¹⁴
Orita M, Iwahana H, Kanazawa H et al. Detection of polymorphisms of human DNA by gel electrophoresis as single-strand conformation polymorphisms. Proc Natl Acad Sci USA 1989;86:2766-70.

[15] ¹⁵
Sarfarazi M. Recent advances in molecular genetics of glaucomas. Hum Mol Genet 1997;6:1667-77.

[16] ¹⁶
Richards JE, Lichter PR, Herman S et al. Probable exclusion of GLCIA as a candidate glaucoma gene in a family with middle age-onset primary open angle glaucoma. Ophthalmology 1996;103:1035-40.

[17] ¹⁷
Avramopoulos D, Kitsos G, Economou-Petersen E et al. Exclusion of one pedigree affected by adult onset primary open angle glaucoma from linkage to the juvenile glaucoma locus on chromosome 1q21-q31. J Mol Genet 1996;33:1043-4.

[18] ¹⁸
Adam MF, Belmouden A, Binisti P et al. Recurrent mutations in a single exon encoding the evolutionary conserved olfactomedin-homology domain of MYOC/TIGR in familial open-angle glaucoma. Hum Mol Genet 1997;6:2091-7.

[19] ¹⁹
Polansky JR, Fauss DJ, Chen P et al. Cellular pharmacology and molecular biology of the trabecular meshwork inducible glucocorticoid response gene product. Ophthalmologica 1997;211:126-39.

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