Identification of mutations in the myocilin (MYOC) gene in Taiwanese patients with juvenile-onset open-angle glaucoma.
OBJECTIVE
To investigate mutations in the promoter and coding regions of the myocilin (MYOC) gene in Taiwanese patients suffering from juvenile-onset open-angle glaucoma (JOAG).


METHODS
MYOC was analyzed for mutations in 48 unrelated Taiwanese probands with JOAG and in 100 healthy control subjects. Genomic DNA was extracted from peripheral blood leukocytes and then subjected to PCR to amplify exons, flanking introns and promoter regions of the MYOC gene. The amplified products were screened for base mutations by autosequence. Data from the two groups were then compared using the chi(2) test. Finally, the levels of MYOC transcripts were predicted by a neural network prediction system to study whether the intron mutations have any effect on the level of mRNA expression.


RESULTS
The analysis revealed four MYOC mutations and six polymorphisms. The prevalence of MYOC gene mutations in this study was 12.5% (6/48). The mutations included one nonsense mutation (Arg46Stop; 3/6), one missense mutation (Val56Ala; 1/6), one intron mutation (c.604+228A>T; 1/6) as well as one mutation in the 3'-untranslated region (c.1515+73G>C; 1/6). In addition, although c.604+228A>T is an intron mutation and does not alter the content of the amino acid residue, the neural network prediction system revealed that it can potentially create a novel accept splice site during transcription. This mutation might affect the protein structure and consequently the normal function of myocilin.


CONCLUSIONS
Our results indicate that the c.136C>T (Arg46Stop), c.158T>C (Val56Ala), c.604+228A>T, and c.1515+73G>C mutations of MYOC may be associated with JOAG. In addition, we suggest that the c.136C>T (Arg46Stop) mutation of MYOC is a hot spot in Taiwanese patients with JOAG.
Yen
Yung-Chang
YC
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Yang
Jiann-Jou
JJ
Chou
Ming-Chih
MC
Li
Shuan-Yow
SY
D020413:3' Untranslated Regions; D000225:Adenine; D017668:Age of Onset; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D018389:Codon, Nonsense; D003598:Cytoskeletal Proteins / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics*; D005902:Glaucoma, Open-Angle / Q000453:epidemiology / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D007438:Introns; D008875:Middle Aged; D009154:Mutation; D020125:Mutation, Missense; D011110:Polymorphism, Genetic; D013624:Taiwan; D013941:Thymine; D000099179:Myocilin
D020413:3' Untranslated Regions; D000225:Adenine; D018389:Codon, Nonsense; D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D013941:Thymine; D000099179:Myocilin