title: Novel myocilin mutation in a Chinese family with juvenile-onset open-angle glaucoma.
abstract: OBJECTIVE
  To search for the genetic cause of juvenile-onset open-angle glaucoma (JOAG) in a Chinese family.
  
  
  METHODS
  In a 3-generation glaucoma family affected with JOAG or ocular hypertension, we screened myocilin (MYOC) and optineurin (OPTN) for mutations and investigated apolipoprotein E (APOE) polymorphisms in 6 family members, 2 of them patients with JOAG, 2 patients with ocular hypertension, and 2 patients who were asymptomatic. Normal controls included 200 unrelated Chinese subjects. The COS-7 cell line was transfected with expression vectors encoding wild-type or mutated MYOC complementary DNA. Cellular and secreted MYOC proteins were characterized by Western blotting.
  
  
  RESULTS
  One missense MYOC mutation, 734G>A: Cys245Tyr, was identified. It occurred in all 4 family members afflicted with JOAG or ocular hypertension but not in asymptomatic family members. No OPTN variations were observed. APOE polymorphism frequencies were similar to those for controls. The Cys245Tyr MYOC mutation cosegregated with the disorder within the family. It was absent in the 200 control subjects. The Cys245Tyr mutant MYOC protein formed homomultimeric complexes that migrated at molecular weights larger than their wild-type counterparts. These mutant complexes remained sequestered intracellularly in COS-7 cells.
  
  
  CONCLUSIONS
  The Cys245Tyr MYOC mutation was the genetic cause of JOAG in this Chinese family. This mutation may alter covalent bonds that formed between MYOC cysteines. Clinical Relevance Genetic tests of MYOC mutations may be beneficial to predict new cases of the disease in families with JOAG.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Bao Jian
authors.initials: BJ
authors.lastname: Fan
authors.forename: Dexter Y L
authors.initials: DY
authors.lastname: Leung
authors.forename: Dan Yi
authors.initials: DY
authors.lastname: Wang
authors.forename: Stéphane
authors.initials: S
authors.lastname: Gobeil
authors.forename: Vincent
authors.initials: V
authors.lastname: Raymond
authors.forename: Pancy O S
authors.initials: PO
authors.lastname: Tam
authors.forename: Dennis S C
authors.initials: DS
authors.lastname: Lam
authors.forename: Chi Pui
authors.initials: CP
authors.lastname: Pang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D044466:Asian People; D019556:COS Cells / Q000378:metabolism; D018797:Cell Cycle Proteins; D002522:Chlorocebus aethiops; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005820:Genetic Testing; D005822:Genetic Vectors; D005902:Glaucoma, Open-Angle / Q000208:ethnology / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007429:Intraocular Pressure; D008297:Male; D026901:Membrane Transport Proteins; D008875:Middle Aged; D020125:Mutation, Missense; D009798:Ocular Hypertension / Q000208:ethnology / Q000235:genetics; D010375:Pedigree; D011110:Polymorphism, Genetic; D035582:Transcription Factor TFIIIA / Q000235:genetics; D014162:Transfection; D000099179:Myocilin
chemical_list: D001057:Apolipoproteins E; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D026901:Membrane Transport Proteins; D035582:Transcription Factor TFIIIA; D000099179:Myocilin; C409460:OPTN protein, human