title: Myocilin gene implicated in primary congenital glaucoma.
abstract: Primary congenital glaucoma (PCG) has been associated with CYP1B1 gene (2p21), with a predominantly autosomal recessive mode of inheritance. Our earlier studies attributed CYP1B1 mutations to only 40% of Indian PCG cases. In this study, we included 72 such PCG cases where CYP1B1 mutations were detected in only 12 patients in heterozygous condition, implying involvement of other gene(s). On screening these patients for mutations in myocilin (MYOC), another glaucoma-associated gene, using denaturing high-performance liquid chromatography followed by sequencing, we identified a patient who was double heterozygous at CYP1B1 (c.1103G>A; Arg368His) and MYOC (c.144G>T; Gln48His) loci, suggesting a digenic mode of inheritance of PCG. In addition, we identified the same MYOC mutation, implicated for primary open angle glaucoma, in three additional PCG patients who did not harbor any mutation in CYP1B1. These observations suggest a possible role of MYOC in PCG, which might be mediated via digenic interaction with CYP1B1 and/or an yet unidentified locus associated with the disease.
authors.affiliation: Kallam Anji Reddy Molecular Genetics Laboratory, Hyderabad, Andhra Pradesh, India.
authors.forename: K
authors.initials: K
authors.lastname: Kaur
authors.forename: A B M
authors.initials: AB
authors.lastname: Reddy
authors.forename: A
authors.initials: A
authors.lastname: Mukhopadhyay
authors.forename: A K
authors.initials: AK
authors.lastname: Mandal
authors.forename: S E
authors.initials: SE
authors.lastname: Hasnain
authors.forename: K
authors.initials: K
authors.lastname: Ray
authors.forename: R
authors.initials: R
authors.lastname: Thomas
authors.forename: D
authors.initials: D
authors.lastname: Balasubramanian
authors.forename: S
authors.initials: S
authors.lastname: Chakrabarti
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D065633:Cytochrome P-450 CYP1B1; D003598:Cytoskeletal Proteins; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005901:Glaucoma / Q000151:congenital* / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D017354:Point Mutation; D000099179:Myocilin
chemical_list: D001189:Aryl Hydrocarbon Hydroxylases; D065633:Cytochrome P-450 CYP1B1; D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D000099179:Myocilin; C585496:CYP1B1 protein, human