title: Compound heterozygote myocilin mutations in a pedigree with high prevalence of primary open-angle glaucoma.
abstract: OBJECTIVE
  To describe the phenotype of ocular hypertension and primary open-angle glaucoma in a family with individuals compound heterozygote for Gln368STOP and Thr377Met myocilin (MYOC) mutations.
  
  
  METHODS
  Family members of the proband underwent comprehensive ocular clinical examination and DNA sequencing for MYOC mutations.
  
  
  RESULTS
  A 34-year-old woman with marked ocular hypertension was found to carry Gln368STOP and Thr377Met MYOC mutations. Three other siblings carried both mutations, while one carried Gln368STOP alone. Three of five siblings had received treatment for ocular hypertension or early glaucoma, with the average age of diagnosis 28 years; one required trabeculectomy at age 27. The mother of the proband was found to be a carrier for Gln368STOP alone, which indicates that her offspring with both Gln368STOP and Thr377Met carry variants on opposing alleles.
  
  
  CONCLUSIONS
  This pedigree is the first report with individuals compound heterozygote for the two most common glaucoma-causing MYOC variants. The combination of mutations manifests a more severe phenotype than either alone. Identification of gene changes associated with glaucoma within the family has enabled unaffected members to stratify their risk of future disease and institute closer monitoring and early treatment.
authors.affiliation: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye & Ear Hospital, East Melbourne, Australia. tkyoung1@gmail.com
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Young
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Souzeau
authors.forename: Lance
authors.initials: L
authors.lastname: Liu
authors.forename: Lisa S
authors.initials: LS
authors.lastname: Kearns
authors.forename: Kathryn P
authors.initials: KP
authors.lastname: Burdon
authors.forename: Jamie E
authors.initials: JE
authors.lastname: Craig
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Ruddle
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001315:Australia; D016022:Case-Control Studies; D003598:Cytoskeletal Proteins / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D005902:Glaucoma, Open-Angle / Q000150:complications / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009798:Ocular Hypertension / Q000150:complications / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D017422:Sequence Analysis, DNA; D012720:Severity of Illness Index; D044465:White People; D000099179:Myocilin
chemical_list: D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D000099179:Myocilin