Absence of optineurin (OPTN) gene mutations in Taiwanese patients with juvenile-onset open-angle glaucoma

Purpose: To investigate sequence variants in the optineyrin (OPTN) gene in patients with juvenil-onset open-angle glaucoma (JOAG) in Taiwan. Methods: We analyzed the sequence variant of OPTN in 51 unrelated Taiwanese probands with JOAG and in 51 control group subjects who did not have JOAG. Genomic DNA was extracted from the individuals and subjected to polymerase chain reaction (PCR) to amplify all 16 exons and flanking introns of OPTN. The amplified products were then screened for base variants by autosequence. Data from the two study groups were then compared using Fisher's exact test and Armitage's trend test. Results: Fifteen variants of OPTN were found in the 51 JOAG patients and 51 unrelated normal controls. Two were missense variants (M98K and K322E), one was a synonymous codon change (T34T), and 12 were changes in the noncoding sequences. Seven of the variants have been reported and eight were novel. All of the sequence changes were found inpatients with JOAG and in the normal controls except for variant c.-233+25C>G, which was found only in the control group. Allelic frequencies of these sequence changes did not differ significantly between patients and controls (p>0.05) except for the variant c.-233+25C>G (p<0.001). Genotype frequencies of c.-233+25C>G was shown to be significant between the two groups using Fisher's two-tailed exact test (p<0.001) and Armitage's trend test (p=6.815e -06). Conclusions: Our data indicate that none of the mutations in OPTN are associated with JOAG. The variant M98K is not a risk factor and the variant c.-233+25C>G may be protective against glaucoma in Taiwanese.