title: Identification of MYOC gene mutation and polymorphism in a large Malay family with juvenile-onset open angle glaucoma.
abstract: OBJECTIVE
  To screen for mutations in the coding region of the myocilin (MYOC) gene in a large Malay family with juvenile-onset open angle glaucoma (JOAG).
  
  
  METHODS
  A total of 122 family members were thoroughly examined and screened for JOAG. Venipuncture was conducted. Genomic DNA was extracted from peripheral blood leukocytes. The presence of a mutation and a polymorphism was ascertained with PCR amplification followed by the direct sequencing technique.
  
  
  RESULTS
  Thirty-two of the 122 screened family members were identified to have JOAG (11 new cases and 21 known cases). An autosomal dominant inheritance pattern with incomplete penetrance was observed. A C→A substitution at position 1440 in exon 3 that changes asparagine (AAC) to lysine (AAA) was identified in affected family members except two probands (III:5 and IV:6). Six probands were identified as having the Asn480Lys mutation but have not developed the disease yet. An intronic polymorphism IVS2 730 +35 G>A was also identified. There was a significant association between Asn480Lys (p<0.001) and IVS2 730+35G>A (p<0.001) in the affected and unaffected probands in this family.
  
  
  CONCLUSIONS
  The Asn480Lys mutation and the IVS2 730+35 G>A polymorphism increased susceptibility to JOAG in this large Malay pedigree. Identifying the MYOC mutations and polymorphisms is important for providing presymptomatic molecular diagnosis.
authors.affiliation: Department of Ophthalmology, University Malaya, Lembah Pantai, Kuala Lumpur Malaysia.
authors.forename: Z
authors.initials: Z
authors.lastname: Mimivati
authors.affiliation: Department of Ophthalmology, University Malaya, Lembah Pantai, Kuala Lumpur Malaysia.
authors.forename: K
authors.initials: K
authors.lastname: Nurliza
authors.affiliation: Human Genome Centre, School of Medical Sciences, University Sains Malaysia, Health Campus, Kota Bharu, Kelantan, Malaysia.
authors.forename: M
authors.initials: M
authors.lastname: Marini
authors.affiliation: Department of Ophthalmology, School of Medical Sciences, University Sains Malaysia Health Campus, Kota Bharu, Kelantan, Malaysia.
authors.forename: At
authors.initials: A
authors.lastname: Liza-Sharmini
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D001483:Base Sequence; D002648:Child; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics*; D005190:Family; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005902:Glaucoma, Open-Angle / Q000453:epidemiology* / Q000235:genetics* / Q000503:physiopathology; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D008296:Malaysia / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D055815:Young Adult; D000099179:Myocilin
chemical_list: D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D000099179:Myocilin