Identification of mutations in the myocilin (MYOC) gene inTaiwanese patients with juvenile-onset open-angle glaucoma

摘要

Purpose: To investigate mutations in the promoter and coding regionsof the myocilin (MYOC) gene in Taiwanese patients suffering fromjuvenile-onset open-angle glaucoma (JOAG).Methods: MYOC was analyzed for mutations in 48 unrelatedTaiwanese probands with JOAG and in 100 healthy control subjects.Genomic DNA was extracted from peripheral blood leukocytes and thensubjected to PCR to amplify exons, flanking introns and promoter regionsof the MYOC gene. The amplified products were screened for basemutations by autosequence. Data from the two groups were then comparedusing the χ2 test. Finally, the levels of MYOC transcriptswere predicted by a neural network prediction system to study whetherthe intron mutations have any effect on the level of mRNA expression.Results: The analysis revealed four MYOC mutations and sixpolymorphisms. The prevalence of MYOC gene mutations in this studywas 12.5% (6/48). The mutations included one nonsense mutation(Arg46Stop; 3/6), one missense mutation (Val56Ala; 1/6), one intronmutation (c.604+228AT; 1/6) as well as one mutation in the3'-untranslated region (c.1515+73GC; 1/6). In addition, althoughc.604+228AT is an intron mutation and does not alter the content ofthe amino acid residue, the neural network prediction system revealedthat it can potentially create a novel accept splice site duringtranscription. This mutation might affect the protein structure andconsequently the normal function of myocilin.Conclusions: Our results indicate that the c.136CT (Arg46Stop),c.158TC (Val56Ala), c.604+228AT, and c.1515+73GC mutationsof MYOC may be associated with JOAG. In addition, we suggest thatthe c.136CT (Arg46Stop) mutation of MYOC is a hot spot inTaiwanese patients with JOAG.