title: Gln48His is the prevalent myocilin mutation in primary open angle and primary congenital glaucoma phenotypes in India.
abstract: OBJECTIVE
  Myocilin gene defects have been originally implicated in primary open angle glaucoma (POAG). Based on multiple reports for the occurrence of Gln48His mutation (c.144G>T; HGMD accession number CM023962) among Indian POAG patients, we wanted to estimate the prevalence of this mutation in primary open angle and primary congenital glaucoma (PCG) in India and assess its role in the causation of the disease.
  
  
  METHODS
  Two hundred cases each of POAG and PCG were screened for the Gln48His mutation by RFLP (AccI) analysis of the PCR amplicons followed by confirmation of the c.144G>T change by direct sequencing.
  
  
  RESULTS
  The Gln48His mutation was detected in 9 different glaucoma patients (four POAG and five PCG). While all four POAG cases were heterozygous, among PCG cases, four were heterozygous and one exhibited homozygous genotype for the mutation. One each of POAG and PCG patients was detected to be heterozygous for CYP1B1 mutation (c.1656C>T, Pro437Leu) and (c.1449G>A, Arg368His), respectively. None of the 300 ethnically matched normal controls contained either the MYOC or CYP1B1 mutation(s).
  
  
  CONCLUSIONS
  The myocilin mutation, Gln48His, represents an allelic condition involving a spectrum of glaucoma phenotypes in Indian populations, and could be a potential risk factor towards disease predisposition among patients of Indian origin. The study also highlights the role of MYOC as a candidate in different glaucoma subtypes that needs to be investigated further.
authors.affiliation: Kallam Anji Reddy Molecular Genetics Laboratory, Brien Holden Eye Research Centre, L. V. Prasad Eye Institute, Hyderabad, India. subho@lvpei.org
authors.forename: Subhabrata
authors.initials: S
authors.lastname: Chakrabarti
authors.forename: Kiranpreet
authors.initials: K
authors.lastname: Kaur
authors.forename: Sreelatha
authors.initials: S
authors.lastname: Komatireddy
authors.forename: Moulinath
authors.initials: M
authors.lastname: Acharya
authors.forename: Koilkonda R
authors.initials: KR
authors.lastname: Devi
authors.forename: Arijit
authors.initials: A
authors.lastname: Mukhopadhyay
authors.forename: Anil K
authors.initials: AK
authors.lastname: Mandal
authors.forename: Seyed E
authors.initials: SE
authors.lastname: Hasnain
authors.forename: Garudadri
authors.initials: G
authors.lastname: Chandrasekhar
authors.forename: Ravi
authors.initials: R
authors.lastname: Thomas
authors.forename: Kunal
authors.initials: K
authors.lastname: Ray
mesh_terms: D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D044466:Asian People / Q000235:genetics; D065633:Cytochrome P-450 CYP1B1; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D005902:Glaucoma, Open-Angle / Q000151:congenital* / Q000208:ethnology / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D007194:India; D007223:Infant; D007231:Infant, Newborn; D010641:Phenotype; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D015995:Prevalence; 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