Sequence analysis of MYOC and CYP1B1 in a Chinese pedigree of juvenile glaucoma with goniodysgenesis.
OBJECTIVE
This study was designed to analyze two candidate genes, myocilin (MYOC) and cytochrome P450 1B1 (CYP1B1), in a Chinese pedigree of juvenile glaucoma with goniodysgenesis.


METHODS
In a three-generation family of juvenile glaucoma with goniodysgenesis (13 members), six of them were patients with glaucoma and the rest were asymptomatic. All members of the family underwent complete ophthalmologic examinations. Exons of MYOC and CYP1B1 were amplified by polymerase chain reaction, sequenced, and compared with a reference database.


RESULTS
Elevated intraocular pressure (IOP) and visual function impairment was found in all patients, and goniodysgenesis was noticed in five of them (nine eyes) with relatively transparent corneas. One MYOC heterozygous mutation, c.1109 C>T (P370L), in exon 3 was identified in all six patients but not in the asymptomatic family members. Two CYP1B1 single nucleotide polymorphisms (SNPs), g.3947 C>G (R48G) in exon 2 and 372-12 C>T in intron 1, were identified in all six patients and but not in the asymptomatic family members except the proband's grandmother. Three SNPs were identified, 730 + 35 A>G in intron 2 of MYOC and g.8131 G>C (V432L) and g.8184 T>C (D449D) in exon 3 of CYP1B1.


CONCLUSIONS
The presence of a P370L mutation of MYOC in all six glaucoma patients suggests a casual association between this mutation and juvenile glaucoma with goniodysgenesis. The possible role of SNPs of CYP1B1 in the pathogenesis of the disease remains to be elucidated.
Chen
Xiaoming
X
Ophthalmic Laboratories and Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, P. R. China.
Yan
Naihong
N
Yun
Hongmin
H
Sun
Jingjing
J
Yu
Man
M
Zhou
Jiumo
J
Cao
Guiqun
G
Yin
Hongbo
H
Li
Mao
M
Liu
Xuyang
X
D000293:Adolescent; D000328:Adult; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases; D044466:Asian People; D001483:Base Sequence; D002681:China; D003316:Corneal Diseases / Q000150:complications* / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005901:Glaucoma / Q000150:complications* / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017422:Sequence Analysis, DNA; 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