A de novo MYOC mutation detected in juvenile open angle glaucoma associated with reduced myocilin protein in aqueous humor

John Kuchtey, Uttio Roy Chowdhury, Colby C. Uptegraft, Michael P. Fautsch, Rachel W. Kuchtey

Research output: Contribution to journalArticle

5 Scopus citations


MYOC mutations were originally identified in patients with juvenile open angle glaucoma (JOAG). Cell culture and mouse studies suggest that MYOC mutations cause glaucoma through a dominant-negative effect on myocilin protein secretion. We tested this hypothesis with patient samples in this study. Glaucoma and control patients underwent complete ocular examination. DNA samples from glaucoma patients, unaffected relatives and controls were used for DNA sequencing of MYOC. Aqueous humor (AH) samples from glaucoma and control patients were obtained at the time of surgery. Myocilin protein in AH was detected by quantitative Western blot analysis. A de novo Val251Ala mutation of MYOC was found to segregate with disease in a family with autosomal dominant JOAG. Myocilin protein was detected in all control AH samples but was nearly undetectable in AH samples from a patient heterozygous for the Val251Ala mutation. Our results using human patient samples are consistent with a dominant-negative effect of pathogenic MYOC mutations on myocilin secretion.

Original languageEnglish (US)
Pages (from-to)292-296
Number of pages5
JournalEuropean Journal of Medical Genetics
Issue number6
StatePublished - Jun 1 2013



  • Aqueous humor
  • De novo mutation
  • Glaucoma
  • Myocilin

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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