RESUMO
PURPOSE: To identify variants in the CYP1B1 gene in northeastern Brazilian patients with primary congenital glaucoma (PCG) and possible genotype-phenotype correlations. MATERIALS AND METHODS: This is a cross-sectional observational study of 17 nonrelated patients with PCG, performed at the Altino Ventura Foundation, Recife, Brazil, between December 2017 and February 2018. All patients underwent an examination, including gathering information from their medical records, slit-lamp examination, fundoscopy, tonography, and measuring corneal diameter and thickness. RESULTS: The mean age at the time of the examination was 27.7 years; 52.9% (n=9) were male, 29.4% (n=5) had history of parental consanguinity. The mean age when the diagnosis was confirmed was 0.53±2.18 years. Horizontal corneal diameter ranged from 12 to 16 mm (mean: 14.05±1.42 mm) and the IOP mean value was 17.31±9.84 mm Hg. Predicted pathogenic variants of the CYP1B1 gene were identified in 4 patients (23.5%). The differences among all clinical parameters did not reach statistical significance between individuals with and without CYP1B1 variants (P-values >0.05). CONCLUSIONS: Two variants which had not been previously related to PCG in Brazil (c.182G>A, c.241T>A) were identified. No statistically significant genotype-phenotype correlations were found.
Assuntos
Citocromo P-450 CYP1B1/genética , Hidroftalmia/genética , Adulto , Brasil , Pré-Escolar , Consanguinidade , Estudos Transversais , Análise Mutacional de DNA , Feminino , Estudos de Associação Genética , Variação Genética , Humanos , Hidroftalmia/diagnóstico , Lactente , Pressão Intraocular/fisiologia , Masculino , Reação em Cadeia da Polimerase , Microscopia com Lâmpada de Fenda , Tonometria Ocular , Adulto JovemRESUMO
PURPOSE: The relationship between clinical data and genetic ancestry in Brazilian patients with primary congenital glaucoma (PCG) was studied. PATIENTS AND METHODS: Thirty patients with PCG and 60 unrelated controls underwent a complete ophthalmological examination. The PCG inclusion criterion was prior surgery with a minimum follow-up of 6 months after the last surgical procedure. Clinical data were recorded and DNA from each individual was extracted and genotyped for a panel of 40 validated ancestry-informative insertion-deletion DNA polymorphisms (indels). RESULTS: Eighteen (60%) children had bilateral disease and 16 (53.3%) were male. The mean age at diagnosis was 6.3 months and surgical follow-up time varied from 8 to 85 months. For the PCG group, the proportion of Europeans, Africans, and Amerindians was 0.784±0.044 (mean±SEM), 0.149±0.035, and 0.067±0.023, respectively, whereas for the control group was 0.730±0.048, 0.132±0.034, and 0.138±0.032, respectively. An increased proportion of African indels was associated with worse surgical prognosis (P=0.036). There was also a statistically significant (P<0.05) positive correlation between axial length and African component (initial: R=0.625; final: R=0.567). CONCLUSIONS: An increased proportion of African indels was associated with worse prognosis for PCG in a mixed population. Genetic ancestry markers may be helpful in assessing risk factors for surgical outcomes in PCG. Further studies are needed to unveil the role of ancestry in heterogeneous populations such as Brazilians with PCG.
Assuntos
População Negra/genética , Etnicidade/genética , Genética Populacional , Hidroftalmia/genética , Mutação INDEL , População Branca/genética , Brasil , Criança , Feminino , Cirurgia Filtrante , Marcadores Genéticos , Genótipo , Humanos , Hidroftalmia/fisiopatologia , Hidroftalmia/cirurgia , Lactente , Recém-Nascido , Pressão Intraocular/genética , Masculino , Tonometria OcularRESUMO
PURPOSE: To determine the spectrum of CYP1B1 gene mutations in Brazilian patients with primary congenital glaucoma, and to correlate the presence of alterations in the CYP1B1 gene sequence with clinical aspects of the disease. MATERIALS AND METHODS: Thirty nonrelated patients with primary congenital glaucoma were studied. Molecular analysis consisted of the codifying region sequencing (exons 2 and 3) and intron/exon boundaries. RESULTS: CYP1B1 gene mutations were present in 9 (30%) of the 30 patients. The structural changes in the CYP1B1 gene previously described in the literature and observed in our study were Q19X, P437L, A443G, g.4340delG, g.7901_79013delGAGTGCAGGCAGA, g.8182delG, and g.8214_8215delG. Three new mutations were observed: 4635delT, 4523delC, and L378Q, in addition to 3793TâC, R48G, A119S, L432V, D449D, and N453S polymorphisms. Patients carrying CYP1B1 gene mutations needed more surgical procedures to control intraocular pressure, either when both eyes were evaluated (P=0.003) or when the worst eye of the patient was analyzed (P=0.011). In relation to the number of affected eyes, all patients with mutations (n=9/9) developed bilateral glaucoma, whereas 11/21 patients without mutations in the CYP1B1 gene had bilateral glaucoma (P=0.013). CONCLUSIONS: In this group of primary congenital glaucoma patients, a 30% mutation frequency in the CYP1B1 gene was observed. The presence of mutations was associated with a more severe form of the disease, requiring more surgeries for intraocular pressure control and with a higher rate of bilateral cases.