Myocilin variants in Indian patients with open-angle glaucoma.
OBJECTIVE
To identify and evaluate MYOC variant alleles among patients with primary open-angle glaucoma (POAG) and age-matched control subjects in an Indian population.


METHODS
Three hundred fifteen patients with POAG and 100 unrelated control subjects from the same ethnic background were enrolled in the study. The coding sequence of MYOC was amplified by polymerase chain reaction using genomic DNA, followed by sequencing of the polymerase chain reaction products. Four single nucleotide polymorphisms were genotyped in different Indian subpopulations comprising 1466 individuals using SEQUENOM's homogeneous MassEXTEND assay.


RESULTS
One novel mutation (Gly399Asp), 6 reported mutations (Gln48His, Thr256Met, Thr353Ile, Gln368Stop, Pro370Leu, and Ala427Thr), and 6 single nucleotide polymorphisms were identified in MYOC. Ala427Thr was identified in a patient with POAG and Parkinson disease. Four single nucleotide polymorphisms genotyped in control subjects were highly heterozygous and displayed a similar pattern of linkage disequilibrium among all linguistic groups.


CONCLUSIONS
MYOC mutations account for 2.2% of POAG cases. The Gln368Stop mutation (common among persons of the white race) found in 2 families does not seem to be of white race origin. Identification of a MYOC mutation (Ala427Thr) in a patient with POAG and Parkinson disease is interesting with respect to reported interaction of myocilin with synucleins.


CONCLUSIONS
Studying the genetics of POAG is helpful for preclinical identification and for better disease management.
Bhattacharjee
Ashima
A
Molecular and Human Genetics Division, Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Rd, Jadavpur, Kolkata 700 032, India.
Acharya
Moulinath
M
Mukhopadhyay
Arijit
A
Mookherjee
Suddhasil
S
Banerjee
Deblina
D
Bandopadhyay
Arun K
AK
Thakur
Sanjay K D
SK
Sen
Abhijit
A
Ray
Kunal
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D005902:Glaucoma, Open-Angle / Q000208:ethnology / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D000099179:Myocilin
D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D000099179:Myocilin