title: Recurrent Myocilin Asn480Lys glaucoma causative mutation arises de novo in a family of Andean descent.
abstract: OBJECTIVE
  To search for MYOC mutations in Peruvian primary open angle glaucoma (POAG) families.
  
  
  METHODS
  Two patients from each of the 11 POAG Peruvian families were screened for sequence variants in MYOC coding exons by conformational sensitive gel electrophoresis and sequencing was performed on the samples indicating probable sequence changes.
  
  
  RESULTS
  We detected 2 families bearing distortions of conformational sensitive gel electrophoresis indicating mutations. Sequencing of these samples revealed coding sequence changes. A native Andean descent family presented with a MYOC mutation, Asn480Lys (C-->G at nucleotide 1440). This is different from the previously reported C-->A change at nucleotide 1440 that causes Asn480Lys in 2 unrelated French and Dutch families with glaucoma of variable expressivity, and indicates a third independent event. A second family of admixed origin showed the presence of the known Arg76Lys polymorphism.
  
  
  CONCLUSIONS
  In the study of MYOC variants in 11 POAG Peruvian families, we have found a family of ethnically admixed origin with polymorphism Arg76Lys and a family of Andean descent bearing a third event of the Asn480Lys, the MYOC mutation that has been reported in the highest number of POAG patients (>80 cases). Analysis of this family could contribute with information about disease manifestation, progression, and treatment response in the context of a distinct genetic background and also climatic, altitude, and socioeconomical conditions.
authors.affiliation: Centro de Genética y Biología Molecular, Facultad de Medicina, Universidad de San Martín de Porres, Instituto de Glaucoma y Catarata, Lima, Peru.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Guevara-Fujita
authors.forename: Rodolfo A
authors.initials: RA
authors.lastname: Perez-Grossmann
authors.forename: Alejandro
authors.initials: A
authors.lastname: Estrada-Cuzcano
authors.forename: Hemant
authors.initials: H
authors.lastname: Pawar
authors.forename: Enrique
authors.initials: E
authors.lastname: Vargas
authors.forename: Julia E
authors.initials: JE
authors.lastname: Richards
authors.forename: Ricardo
authors.initials: R
authors.lastname: Fujita
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D004587:Electrophoresis, Agar Gel; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005902:Glaucoma, Open-Angle / Q000208:ethnology / Q000235:genetics* / Q000601:surgery; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D007199:Indians, South American / Q000235:genetics*; D007429:Intraocular Pressure; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010568:Peru / Q000453:epidemiology; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012008:Recurrence; D017422:Sequence Analysis, DNA; D014130:Trabeculectomy; D000099179:Myocilin
chemical_list: D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D000099179:Myocilin