Contributions of MYOC and CYP1B1 mutations to JOAG.
OBJECTIVE
To investigate the role of MYOC and CYP1B1 in Iranian juvenile open angle glaucoma (JOAG) patients.


METHODS
Twenty-three JOAG probands, their available affected and unaffected family members, and 100 ethnically matched control individuals without history of ocular disease were recruited. Clinical examinations of the probands included slit lamp biomicroscopy, intraocular pressure (IOP) measurement, gonioscopic evaluation, fundus examination, and perimetry measurement. Familial cases were classified according to the mode of inheritance. Exons of MYOC and CYP1B1 were sequenced, and novel variations assessed in the control individuals. Potential disease-associated variations were tested for segregation with disease status in available family members.


RESULTS
The mode of inheritance of the disease in the families of four probands (17.4%) appeared to be autosomal dominant and in at least eight (34.8%) to be autosomal recessive. Four patients carried MYOC mutations, and an equal number carried CYP1B1 mutations. The MYOC mutations were heterozygous; two of them (p.C8X and p.L334P) are novel, and one codes for the shortest truncated protein so far reported. Autosomal recessive inheritance was consistent with inheritance observed in families of patients carrying CYP1B1 mutations. All these patients carried homozygous mutations.


CONCLUSIONS
MYOC and CYP1B1 contributed equally to the disease status of the Iranian JOAG patients studied. The contribution of the two genes appeared to be independent in that no patient carried mutations in both genes. The fraction of Iranian patients carrying MYOC mutations was comparable to previously reported populations.
Bayat
Behnaz
B
National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.
Yazdani
Shahin
S
Alavi
Afagh
A
Chiani
Mohsen
M
Chitsazian
Fereshteh
F
Tusi
Betsabeh Khoramian
BK
Suri
Fatemeh
F
Narooie-Nejhad
Mehrnaz
M
Sanati
Mohammad H
MH
Elahi
Elahe
E
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D018912:Arabs / Q000235:genetics*; D001189:Aryl Hydrocarbon Hydroxylases; D002648:Child; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics*; D005799:Genes, Dominant; D005808:Genes, Recessive; D005902:Glaucoma, Open-Angle / Q000453:epidemiology* / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D007492:Iran; D000099179:Myocilin
D001189:Aryl Hydrocarbon Hydroxylases; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System; D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D000099179:Myocilin; C585496:CYP1B1 protein, human