Childhood-onset primary open angle glaucoma in a Canadian kindred: clinical and molecular genetic features

Ophthalmic Genet. 1999 Dec;20(4):211-8. doi: 10.1076/opge.20.4.211.2275.

Abstract

Objective: To describe the clinical features and identify the molecular etiology of childhood-onset primary open angle glaucoma (POAG) in a Canadian kindred.

Methods: Members of a Canadian Caucasian family with POAG were examined and DNA obtained. Single-strand conformation polymorphism analysis was performed using reported primers from exon 3 of the myocilin gene. A single-stranded conformation polymorphism was characterized by polymerase chain reaction-based sequencing.

Results: Two affected half-sibs had onset of severe glaucoma at age 3 and 9. Their mother had lost vision in one eye from glaucoma by age 17. All three affected subjects had undergone bilateral glaucoma filtering surgery. Both fathers were unaffected. A single-stranded conformation polymorphism was identified in the mother and the two affected daughters and was absent in one father. A single base change from C-->T at nucleotide position 1109 was identified in the affected members of the family by direct sequencing. This mutation, which causes a nonconservative amino acid change (Pro370Leu), was not found on 192 normal chromosomes from Caucasian individuals.

Conclusion: We report a Canadian family with childhood-onset, severe POAG due to a mutation in the myocilin gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Amino Acid Substitution
  • Base Sequence
  • Canada
  • Child
  • Child, Preschool
  • Cytoskeletal Proteins
  • DNA / chemistry
  • DNA / genetics
  • DNA Mutational Analysis
  • Eye Proteins / genetics
  • Family Health
  • Female
  • Glaucoma, Open-Angle / genetics*
  • Glaucoma, Open-Angle / pathology
  • Glycoproteins / genetics
  • Humans
  • Male
  • Pedigree
  • Point Mutation
  • Polymorphism, Single-Stranded Conformational

Substances

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