PRIMARY OPEN-ANGLE GLAUCOMA DUE TO MUTATIONS IN THE MYOC GENE
Authors:
A. Vergaro 1,2; L. Rezková 1; M. Fichtl 1; J. Jedličková 2; Ľ. Ďuďáková 2; E. Růžičková 1; P. Lišková 1,2
Authors place of work:
Oční klinika, 1. lékařská fakulta, Univerzita Karlova a Všeobecná fakultní nemocnice v Praze
1; Laboratoř pro studium vzácných nemocí, Klinika pediatrie a dědičných poruch metabolismu, 1. lékařská fakulta Univerzity Karlovy a Všeobecná fakultní nemocnice v Praze
2
Published in the journal:
Čes. a slov. Oftal., 78, 2022, No. 5, p. 242-248
Category:
Original Article
doi:
https://doi.org/10.31348/2022/25
Summary
Aim: Mutations in the myocilin gene (MYOC) cause trabecular dysfunction and thus are involved in the pathogenesis of primary open-angle glaucoma (POAG). The aim of this study was to characterize and describe the clinical findings in two Czech families with POAG due to pathogenic variants in the MYOC gene.
Material and methods: Members of the two families affected by POAG underwent complete ophthalmological examination. In the proband from the first family, a direct sequencing of the three most frequent mutations in the MYOC gene was performed, and in the proband from the second family, an exome sequencing was performed. Other family members underwent targeted tests using direct sequencing.
Results: In total, 10 individuals diagnosed with POAG aged 20–70 years (mean 32.2 years, SD ±10,9 years) were examined. Eight of them showed advanced glaucomatous neuropathy with severe changes in the retinal nerve fiber layer. Clinical signs of POAG were present in six individuals in the third decade of life already; another four developed POAG during the fourth decade of life. Eight out of 10 patients had to undergo filtration surgery. Surgery was performed within 1 to 7 years of diagnosis, but mostly was performed within 2 years of glaucoma diagnosis. In the first family, MYOC variant c.1099G>A p.(Gly367Arg) was shown in the affected family members; in the second family MYOC variant c.1440C>A p.(Asn480Lys), both in heterozygous state. The changes were assessed as pathogenic.
Conclusion: Our study is the first to describe mutations in the MYOC gene causing POAG in Czech patients. Genetic testing may be recommended for this diagnosis, especially in individuals with early presentation and a positive family history. Carriers of pathogenic variants of the MYOC gene have a lifetime risk of developing POAG of more than 50% and the course of their disease is often more aggressive, requiring surgical intervention to permanently control the intraocular pressure.
Keywords:
Mutation – Myocilin – primary open angle glaucoma – juvenile glaucoma
Zdroje
1. Takamoto M, Araie M. Genetics of primary open angle glaucoma. Japanese Journal of Ophthalmology. 2014;58(1):1-15.
2. Khawaja AP, Viswanathan AC. Are we ready for genetic testing for primary open-angle glaucoma? Eye. 2018;32(5):877-883.
3. Wiggs JL, Pasquale LR. Genetics of glaucoma. Hum Mol Genet. 2017;26(R1):R21-R7.
4. Wang HW, Li MZ, Zhang ZZ, Xue HF, Chen X, Ji Y. Physiological function of myocilin and its role in the pathogenesis of glaucoma in the trabecular meshwork (Review). Int J Mol Med. 2019;43(2):671-681.
5. Resch ZT, Fautsch MP. Glaucoma-associated myocilin: A better understanding but much more to learn. Experimental Eye Research. 2009;88(4):704-712.
6. Chung HK, Han YK, Oh S, Kim SH. Comparison of Optical Coherence Tomography Measurement Reproducibility between Children and Adults. PLoS One. 2016;11(1):e0147448.
7. Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405-424.
8. Iliev ME, Bodmer S, Gallati S, et al. Glaucoma phenotype in a large Swiss pedigree with the myocilin Gly367Arg mutation. Eye. 2008;22(7):880-888.
9. Gupta V, Somarajan BI, Gupta S, et al. The mutational spectrum of Myocilin gene among familial versus sporadic cases of Juvenile onset open angle glaucoma. Eye. 2021;35(2):400-408.
10. Faucher M, Anctil JL, Rodrigue MA, et al. Founder TIGR/myocilin mutations for glaucoma in the Quebec population. Hum Mol Genet. 2002;11(18):2077-2090.
11. Mansergh FC, Kenna PF, Ayuso C, Kiang AS, Humphries P, Farrar GJ. Novel mutations in the TIGR gene in early and late onset open angle glaucoma. Hum Mutat. 1998;11(3):244-251.
12. Chen J, Cai SP, Yu W, et al. Sequence analysis of MYOC and CYP1B1 in a Chinese pedigree of primary open-angle glaucoma. Mol Vis. 2011;17:1431-1435.
13. Mimivati Z, Nurliza K, Marini M, Liza-Sharmini A. Identification of MYOC gene mutation and polymorphism in a large Malay family with juvenile-onset open angle glaucoma. Mol Vis. 2014;20:714-723.
14. Rose R, Balakrishnan A, Muthusamy K, Arumugam P, Shanmugam S, Gopalswamy J. Myocilin mutations among POAG patients from two populations of Tamil Nadu, South India, a comparative analysis. Mol Vis. 2011;17(349-53):3243-3253.
15. Guevara-Fujita ML, Perez-Grossmann RA, Estrada-Cuzcano A, et al. Recurrent Myocilin Asn480Lys glaucoma causative mutation arises de novo in a family of Andean descent. J Glaucoma. 2008;17(1):67-72.
16. Hulsman CA, De Jong PT, Lettink M, Van Duijn CM, Hofman A, Bergen AA. Myocilin mutations in a population-based sample of cases with open-angle glaucoma: the Rotterdam Study. Graefe’s Archive for Clinical and Experimental Ophthalmology. 2002;240(6):468-474.
17. Mackey DA, Healey DL, Fingert JH, et al. Glaucoma phenotype in pedigrees with the myocilin Thr377Met mutation. Arch Ophthalmol. 2003;121(8):1172-1180.
18. Taniguchi F, Suzuki Y, Shirato S, Araie M. The Gly367Arg mutation in the myocilin gene causes adult-onset primary open-angle glaucoma. Jpn J Ophthalmol. 2000;44(4):445-8.
19. Adam MF, Belmouden A, Binisti P, et al. Recurrent Mutations in a Single Exon Encoding the Evolutionarily Conserved Olfactomedin- Homology Domain of TIGR in Familial Open-Angle Glaucoma. Hum Mol Genet. 1997;6(12):2091-2097.
20. Rose R, Balakrishnan A, Muthusamy K, Arumugam P, Shanmugam S, Gopalswamy J. Myocilin mutations among POAG patients from two populations of Tamil Nadu, South India, a comparative analysis. Mol Vis. 2011;17:3243-3253.
Štítky
OphthalmologyČlánok vyšiel v časopise
Czech and Slovak Ophthalmology
2022 Číslo 5
Najčítanejšie v tomto čísle
- SARS-COV-2 PANDEMIC FROM THE OPHTHALMOLOGIST`S PERSPECTIVE. A REVIEW
- CHELATION OF BAND KERATOPATHY IN LONG-TERM MONITORING
- ATYPICAL FORMS OF EYE TOXOPLASMOSIS IN CHILDHOOD. CASE REPORTS
- PRIMARY OPEN-ANGLE GLAUCOMA DUE TO MUTATIONS IN THE MYOC GENE