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Purpose: To both characterize the clinical features of large primary open angle glaucoma (POAG) pedigree from a village in southern India and to investigate the genetic basis of their disease. Materials and methods: Eighty-four members of a large pedigree received complete eye examinations including slit lamp examination, tonometry, gonioscopy, and ophthalmoscopy. Some were further studied with perimetry. Those diagnosed with POAG were tested for disease-causing mutations in the myocilin and optineurin genes with Sanger sequencing. Results: Fourteen of 84 family members were diagnosed with POAG, while eight were clinically judged to be POAG-suspects. The family structure and the pattern of glaucoma in the pedigree are complex. Features of glaucoma in this pedigree include relatively early age at diagnosis (mean 50 ± 14 years) and maximum intraocular pressures ranging from 14 to 36 mm Hg with a mean of 23 mm Hg ± 6.5 mm Hg. Patients had an average central corneal thickness (mean 529 ± 37.8 microns) and moderate cup-to-disc ratios (0.74 ± 0.14). No mutations were detected in myocilin, optineurin, or TANK binding kinase 1 (TBK1). Conclusions: We report a five-generation pedigree with a complex pattern of POAG inheritance that includes 22 POAG patients and glaucoma suspects. Although the familial clustering of POAG in this pedigree is consistent with dominant inheritance of a glaucoma-causing gene, mutations were not detected in genes previously associated with autosomal dominant glaucoma, suggesting the involvement of a novel disease-causing gene in this pedigree. [ABSTRACT FROM AUTHOR]

Purpose: Glaucoma is the second leading cause of blindness. In India. ∼1.5 million people are blind due to glaucoma. Mutations in the MYOC gene located at the GLCIA locus on chromosome Iq21-q31 have been found in patients with juvenile-onset primary open-angle glaucoma (J-POAG).The purpose of the present study was to identify the genetic cause of glaucoma in a four-generation Indian family affected with J-POAG. Methods: Peripheral blood samples were obtained from individuals for genomic DNA isolation. To determine if this family was linked to the GLCIA locus, haplotyping analysis was carried out using microsatellite markers from the GLC1A candidate region. Exon-specific primers from exon 3 of the MYOC gene were used to amplify DNA samples from individuals. Mutation analysis was carried out using PCR-SSCP and DNA sequence analyses. Results: Pedigree analysis suggested that glaucoma in this family segregated as an autosomal dominant trait. Of six patients, five had J-POAG and one had adult-onset POAG (A-POAG). Haplotype analysis suggested linkage of this family to the GLC1A locus. Mutation and sequence analyses showed a novel missense mutation, c.821C > G (p.P274R), in the C-terminal olfactomedin domain coded by exon 3 of the MYOC gene. One patient was found to be homozygous for this mutation with a severe phenotype. Conclusions: This study reports a novel missense mutation in a four-generation Indian family with all but one member affected with J-POAG. The total number of mutations described so far in the MYOC gene, including the one reported here, is 59 with a clustering of 52 mutations, in exon 3. [ABSTRACT FROM AUTHOR]