Full text
| |
| Author(s): |
Paulo Vinicius Svidnicki
Total Authors: 1
|
| Document type: | Doctoral Thesis |
| Press: | Campinas, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas |
| Defense date: | 2018-01-24 |
| Examining board members: |
Mônica Barbosa de Melo;
Cláudia Vianna Maurer Morelli;
Andrea Trevas Maciel Guerra;
Jayter Silva de Paula;
Augusto Paranhos Junior
|
| Advisor: | Mônica Barbosa de Melo |
| Abstract | |
Glaucoma is a neurodegenerative disease of multifactorial etiology that includes several eye disorders whose common features are the progressive damage of the optic nerve with vision loss. It is a major cause of irreversible blindness in the world. Primary open angle glaucoma (POAG) is the most common type of the disease, while Juvenile Open Angle Glaucoma (JOAG) is an earlier onset and more severe form of glaucoma. This disease is rarely detected early, because it is asymptomatic initially, when the treatment prevents permanent loss of visual function. Thus, identification of genetic factors is important to help in early diagnosis and to establish an appropriate clinical outcome. Glaucoma-associated mutations in the MYOC gene are responsible for approximately 3¿5% of POAG and 10¿30% of JOAG. The CYP1B1 gene has been associated with primary congenital glaucoma (PCG) and also has been implicated in juvenile and adult onset forms of glaucoma in several ethnic groups worldwide. CYP1B1 and MYOC might act through a common biochemical pathway with CYP1B1 acting as a modifier for MYOC. In this study, we evaluated the variants in the coding regions of MYOC and CYP1B1 genes in 100 non-related patients with JOAG and 200 controls through Sanger sequencing. In this study, we also studied a JOAG family through exome sequencing. Our results show that MYOC mutations have a great importance in JOAG cases in this cohort, corresponding to 34% of total cases. CYP1B1 mutations, on the other hand were present in only 2 % and its polymorphisms were not associated with JOAG clinical outcomes. In this study, we also detected one damaging mutation in the APEX1 gene segregating in a family harboring JOAG. We performed a functional study using Zebrafish morpholino knockdown for the Apex1 gene to validate this candidate gene that has never been proved to be associated with JOAG. Morphants for the APEX1 gene presented an interesting phenotype, with a "coat" around the eye, diminished eye size and retinal layers disorganization. This data indicates that APEX1 could be a new glaucoma gene (AU) | |
| FAPESP's process: | 13/17958-2 - Study of genetic aspects of primary open-angle glaucoma by whole exome sequencing |
| Grantee: | Paulo Vinicius Svidnicki |
| Support Opportunities: | Scholarships in Brazil - Doctorate |