Truncations in the TIGR gene in individuals with and without primary open-angle glaucoma

Invest Ophthalmol Vis Sci. 2000 May;41(6):1386-91.

Abstract

Purpose: To investigate the coding exons in the trabecular meshwork-induced glucocorticoid response protein (TIGR) gene for mutations in primary open-angle glaucoma (POAG) in Chinese subjects.

Methods: Ninety-one Chinese patients with POAG and 113 of their family members without glaucoma were screened for sequence alterations in the TIGR gene by polymerase chain reaction, conformation-sensitive gel electrophoresis, and DNA sequencing. One hundred thirty-two unrelated individuals without glaucoma, aged 50 years or more, were studied as control subjects.

Results: Five sequence variants that lead to amino acid changes were identified. One was novel: Arg91Stop in one patient with POAG. Four had been reported: Arg46Stop in subjects with and without POAG, including an unaffected 77-year-old woman homozygous for Arg46Stop; Gly12Arg in subjects without glaucoma; and Asp208Glu and Thr353Ile in subjects with and without POAG. The previously reported 1-83(G-->A) and Arg76Lys polymorphisms were detected in both patients and controls and always occurred together.

Conclusions: A different pattern of TIGR sequence variants exists in the Chinese than in non-Chinese populations. No common TIGR mutation that causes POAG was found. The occurrence of subjects without glaucoma who are heterozygous or homozygous for Arg46Stop suggests that reduction in the amount of TIGR protein does not cause glaucoma. Thus, the TIGR missense mutations known to cause POAG probably do not cause glaucoma by inactivating a normal TIGR function, but rather through the gain of a pathologic function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Asians / genetics
  • Child
  • Cytoskeletal Proteins / genetics*
  • DNA Mutational Analysis
  • DNA Primers / chemistry
  • Eye Proteins / genetics*
  • Female
  • Glaucoma, Open-Angle / ethnology
  • Glaucoma, Open-Angle / genetics*
  • Glaucoma, Open-Angle / pathology
  • Glycoproteins / genetics*
  • Hong Kong / epidemiology
  • Humans
  • Male
  • Middle Aged
  • Mutation, Missense*
  • Polymorphism, Genetic
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Analysis, DNA
  • Trabecular Meshwork / pathology

Substances

  • Cytoskeletal Proteins
  • DNA Primers
  • Eye Proteins
  • Glycoproteins
  • trabecular meshwork-induced glucocorticoid response protein