Avaliação do gene CYP1B1 e da ancestralidade genômica no glaucoma congênito primário

• Ano de defesa: 2013
• Autor(a) principal: Hélvia Tamar Rolim Lima
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; UFMG
• Palavras-chave em Português: Indels; Ancestralidade; Mutação; Gene CYP1B1; Glaucoma congênito primário; Glaucoma; Glaucoma/congênito; Malha trabecular/anormalidades; Grupo com ancestrais do continente africano; Cegueira/etiologia; Mutação INDEL; Glaucoma/genética; Glaucoma/etnologia; Fatores de risco; Oftalmologia; Criança; Marcadores genéticos
• Link de acesso: http://hdl.handle.net/1843/BUBD-9ESECJ

INTRODUCTION: The primary congenital glaucoma is an isolated trabeculodysgenesis causing obstruction of aqueous humor outflow and subsequent increase in intraocular pressure, being a major cause of blindness in children. It is the most common form of glaucoma in childhood and has been associated with changes in the CYP1B1 gene. In a much smaller scale, the LTBP2 gene has also been reported as another cause of the disease. PURPOSE: Thirty children with primary congenital glaucoma and a minimum follow-up of six months after the last surgery and 60 control individuals underwent eye examination and peripheral blood collection. Clinical data were collected, DNA extracted and the CYP1B1 gene sequenced. The study of genomic ancestry was conducted using 40 insertion-deletion markers (indels). RESULTS: We found 10 mutations in CYP1B1 in 11 patients (36.7%), three of them new mutations (p.Gln109Stop, p.Pro476.Ser476, fs.1416delC). Children with PCG had an ancestry ratio of European, African and Amerindian of 0.784 ± 0.044 (mean ± SE), 0.149 ± 0.035 and 0.067 ± 0.023, respectively, and the control group was 0.730 ± 0.048, 0.132 ± 0.034 and 0.138 ± 0.032, respectively. Differences in these ratios between probandos and controls were not significant (p>0.05). There were no significant differences in the components of ancestry among probands with and without mutations in CYP1B1. A higher index of African ancestry was associated with worse prognosis. CONCLUSIONS: CYP1B1 gene is the main cause of primary congenital glaucoma. However, absence of mutations in 63.3% of children with primary congenital glaucoma suggests the involvement of other gene(s) or molecular causes in the pathogenesis of this disease. The African ancestry component appears to influence the algorithms, perhaps acting as a risk factor, when present in high proportion. In addition, a higher ratio of African ancestry was associated with a worse prognosis. Further studies are needed to establish the role of other genes and of genomic ancestry in primary congenital glaucoma in admixed populations such as that of Brazil.