Absence of myocilin and optineurin mutations in a large Philippine family with juvenile onset primary open angle glaucoma

Mol Vis. 2004 Nov 9:10:851-6.


Purpose: To analyze the role of the two primary open angle glaucoma (POAG) genes, myocilin (MYOC) and optineurin (OPTN), in a large Philippine family segregating autosomal dominant juvenile onset open angle glaucoma (JOAG).

Methods: The coding sequences of the MYOC and OPTN genes were screened in 27 family members by polymerase chain reaction and direct sequencing. The specific MYOC promoter polymorphism (MYOC.mtl) was identified by restriction endonuclease assay. All of the ABI MD-10 microsatellite markers on chromosomes 1, 2, 3, 7, 8, and 10, which harbor the six known POAG loci, were analyzed for linkage with POAG.

Results: No mutation was identified in this large kindred. Instead, three polymorphisms (-80G->A, -1000G->C, R76K) in MYOC and four polymorphisms (T34T, M98K, R545Q, IVS7+24G->A) in OPTN were found. All markers flanking the six known POAG loci gave LOD scores not more than 1.1. Non-parametric linkage analysis for all these markers resulted in p values more than 0.05.

Conclusions: Both mutation testing and linkage analysis provide strong evidence against MYOC and OPTN being the causative gene in this large family. It indicates that unidentified genes will underlie the occurrence of glaucoma in this family.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cell Cycle Proteins
  • Cytoskeletal Proteins
  • DNA Mutational Analysis
  • Eye Proteins / genetics*
  • Female
  • Genes, Dominant
  • Genetic Linkage
  • Glaucoma, Open-Angle / ethnology
  • Glaucoma, Open-Angle / genetics*
  • Glycoproteins / genetics*
  • Humans
  • Intraocular Pressure
  • Male
  • Membrane Transport Proteins
  • Microsatellite Repeats
  • Mutation*
  • Pedigree
  • Philippines / epidemiology
  • Polymorphism, Genetic
  • Transcription Factor TFIIIA / genetics*


  • Cell Cycle Proteins
  • Cytoskeletal Proteins
  • Eye Proteins
  • Glycoproteins
  • Membrane Transport Proteins
  • OPTN protein, human
  • Transcription Factor TFIIIA
  • trabecular meshwork-induced glucocorticoid response protein