Genetic analysis of an Indian family with members affected with juvenile-onset primary open-angle glaucoma

M. Markandaya, T. K. Ramesh, V. Selvaraju, Syril Dorairaj, Ravi Prakash, Jyoti Shetty, A. Kumar

Research output: Contribution to journalArticle

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Abstract

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 GLC1A locus on chromosome 1q21-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 GLC1A 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.

Original languageEnglish (US)
Pages (from-to)11-23
Number of pages13
JournalOphthalmic Genetics
Volume25
Issue number1
DOIs
StatePublished - Mar 1 2004
Externally publishedYes

Fingerprint

Glaucoma
Mutation
Exons
Missense Mutation
Genes
Single-Stranded Conformational Polymorphism
DNA
Blindness
Pedigree
DNA Sequence Analysis
Microsatellite Repeats
Haplotypes
Sequence Analysis
Cluster Analysis
Primary Open Angle Glaucoma
India
Chromosomes
Phenotype
Polymerase Chain Reaction

Keywords

  • Glaucoma
  • GLC1A
  • Homozygous mutation
  • J-POAG
  • MYOC
  • Myocilin

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Ophthalmology
  • Genetics(clinical)

Cite this

Genetic analysis of an Indian family with members affected with juvenile-onset primary open-angle glaucoma. / Markandaya, M.; Ramesh, T. K.; Selvaraju, V.; Dorairaj, Syril; Prakash, Ravi; Shetty, Jyoti; Kumar, A.

In: Ophthalmic Genetics, Vol. 25, No. 1, 01.03.2004, p. 11-23.

Research output: Contribution to journalArticle

Markandaya, M. ; Ramesh, T. K. ; Selvaraju, V. ; Dorairaj, Syril ; Prakash, Ravi ; Shetty, Jyoti ; Kumar, A. / Genetic analysis of an Indian family with members affected with juvenile-onset primary open-angle glaucoma. In: Ophthalmic Genetics. 2004 ; Vol. 25, No. 1. pp. 11-23.
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AU - Markandaya, M.

AU - Ramesh, T. K.

AU - Selvaraju, V.

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AU - Kumar, A.

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N2 - 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 GLC1A locus on chromosome 1q21-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 GLC1A 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.

AB - 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 GLC1A locus on chromosome 1q21-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 GLC1A 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.

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KW - MYOC

KW - Myocilin

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