RESUMEN
In 32 patients with primary congenital glaucoma (PCG), a search for mutations in the myocilin (MYOC), cytochrome P450B1 (CYP1B1), and WDR36 genes was performed. The Q368X mutation in myocilin gene, typical of the patients with adult-onset primary open-angle glaucoma (POAG), was not detected in the PCG patients. Screening of the CYP1B1 introns 2 and 3 for the presence of mutations in PCG patients revealed only six DNA polymorphisms, including IVS1-12ntT>C (g.3793 T>C), A119S (g.4160 G>T; GCC>TCC), G188G (g.4369 C>A; GGC>GGA), L432V (G.8131 C>G; CTG>GTG), D449D (g.8184 C>T; GAC>GAT), and N453S (g.8195 A>G; AAC>AGC) (nucleotide numbering is given in accordance with the GenBank sequence U56438). In the groups of PCG patients and donors without eye diseases, the frequencies of these variants were not statistically significantly different, pointing to the neutrality of these polymorphisms. Furthermore, the CYP1B1 polymorphism L432V, considered to be associated with POAG in some world populations, was not associated with this disease in the patients from St. Petersburg. DNA collections obtained from the POAG and PCG patients and from the control group were tested for the carriage of the worldwide distributed mutations of the WRD36 gene, D658G, R529Q, A449T, and N355S. D658G variant was found with equally low frequencies in the groups of POAG and PCG patients, as well as in the control group. Mutations A449T and R529Q were found only once each, while mutation N355S was not detected in any of the groups examined. Our results indicate that the WDR36 variants make no substantial contribution to the development of POAG and PCG in the patients from St. Petersburg and represent normal DNA polymorphism. It is likely that in most of the PCG patients from the population examined the disease is not associated with the CYP1B1 gene defects.
Asunto(s)
Sustitución de Aminoácidos , Sistema Enzimático del Citocromo P-450/genética , Proteínas del Ojo/genética , Glaucoma de Ángulo Abierto/congénito , Mutación Missense , Polimorfismo de Nucleótido Simple , Adulto , Hidrocarburo de Aril Hidroxilasas , Citocromo P-450 CYP1B1 , Proteínas del Citoesqueleto/genética , Femenino , Glicoproteínas/genética , Humanos , Intrones/genética , Masculino , Federación de RusiaRESUMEN
A collection of DNA samples obtained from primary open-angle glaucoma (POAG) patients from St. Petersburg was analyzed for single-strand conformation polymorphism (SSCP) to reveal sequence variants in exon 3 of the myocilin gene (MYOC/TIGR) and in exons 4 and 5 of the optineurin gene (OPTN), where most of the mutations revealed worldwide are located. The Q368X mutation (c. 1102 C --> T) in exon 3 of MYOC/TIGR was detected in 1.2% (2/170) of the POAG patients from St. Petersburg, i.e., with the frequency close to that observed in other world populations. Three known polymorphisms in exon 3 of MYOC/TIGR, Y347Y (c. 1041 T --> C) (12.4%), T325T (c. 975 G --> A) (0.6%), and K398R (c. 1193 A --> G) (0.6%) were also detected. No statistically significant differences in frequencies of these polymorphisms were revealed between the POAG patient and control groups. The L41L polymorphism (c. 433 G --> A) in exon 4 of OPTN was detected in 2.9% of probands and in 1% of controls. The frequency of heterozygotes for the M98K polymorphism (c. 603 T --> A) in the OPTN exon 5 was statistically significantly higher (P = 0.036; Fisher's exact test) among the POAG patients (6.5%) than among the controls (1%). In the sample examined the E50K mutation, typical of the patients with pseudonormal intraocular pressure glaucoma, was not found.