title: New mutation in the myocilin gene segregates with juvenile-onset open-angle glaucoma in a Brazilian family.
abstract: Mutations in the myocilin gene (MYOC) account for most cases of autosomal dominant juvenile-onset open-angle glaucoma (JOAG), an earlier and more severe form of POAG. We accessed seven members of a Brazilian JOAG family by clinical and molecular investigation. Four out of seven family members were diagnosed with JOAG. All of these patients presented high intraocular pressure and two of them were bilaterally blind. The disease onset varied from 20 to 30years old. There was a nine-year-old family member who had not yet manifested the disease, although he was also a carrier of the mutation. Ophthalmologic examination included: evaluation of the visual field and optic disc, intraocular pressure measurement, and gonioscopy. The three exons and intron/exon junctions of the MYOC gene were screened for mutations through direct sequencing of PCR-amplified DNA fragments. Mutation screening revealed an in-frame mutation in the third exon of the MYOC gene: an insertion of six nucleotides between the cDNA positions 1187 and 1188 (c.1187_1188insCCCAGA, p.D395_E396insDP). This mutation presented an autosomal dominant pattern of inheritance, segregating with the disease in four family members for three generations, and it was absent in 60 normal controls. We also performed a computational structure modeling of olfactomedin-like domain of myocilin protein and conducted in silico analysis to predict the structural changes in the myocilin protein due to the presence of the mutation. These findings may be important for future diagnosis of other presymptomatic family members, as well as for the increase of the panel of MYOC mutations and their effects on phenotype.
authors.affiliation: Centro de Biologia Molecular e Engenharia Genética (CBMEG), Universidade Estadual de Campinas, Avenida Cândido Rondon 400, Cidade Universitária Zeferino Vaz, Distrito de Barão Geraldo, P.O. Box 6010, 13083-875, Campinas, SP, Brazil. ca.ayumi@gmail.com
authors.forename: Carolina Ayumi
authors.initials: CA
authors.lastname: Braghini
authors.forename: Izabella Agostinho Pena
authors.initials: IA
authors.lastname: Neshich
authors.forename: Goran
authors.initials: G
authors.lastname: Neshich
authors.forename: Fernanda Caroline
authors.initials: FC
authors.lastname: Soardi
authors.forename: Maricilda Palandi
authors.initials: MP
authors.lastname: de Mello
authors.forename: Vital Paulino
authors.initials: VP
authors.lastname: Costa
authors.forename: José Paulo Cabral
authors.initials: JP
authors.lastname: de Vasconcellos
authors.forename: Mônica Barbosa
authors.initials: MB
authors.lastname: de Melo
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000595:Amino Acid Sequence; D001938:Brazil; D019295:Computational Biology; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005902:Glaucoma, Open-Angle / Q000175:diagnosis / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics*; D006068:Gonioscopy; D006801:Humans; D007429:Intraocular Pressure / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D009885:Ophthalmology; D009898:Optic Disk / Q000473:pathology; D010375:Pedigree; D010641:Phenotype; D017434:Protein Structure, Tertiary; D014794:Visual Fields / Q000235:genetics; D055815:Young Adult; D000099179:Myocilin
chemical_list: D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D000099179:Myocilin