TY - JOUR
T1 - Genotype and Phenotype Correlations in Congenital Glaucoma
T2 - CYP1B1 Mutations, Goniodysgenesis, and Clinical Characteristics
AU - Hollander, David A.
AU - Sarfarazi, Mansoor
AU - Stoilov, Ivaylo
AU - Wood, Irmgard S.
AU - Fredrick, Douglas R.
AU - Alvarado, Jorge A.
N1 - Funding Information:
This study was supported by the Peter and Mimi Haas Foundation, That Man May See (TMMS) Inc, San Francisco, California, Research to Prevent Blindness, New York, New York, and National Institutes of Health (EY011095), Bethesda, Maryland. The authors indicate no financial conflict of interest. Involved in collection, management, analysis and interpretation of data, and preparation of the data and revision including references (D.A.H., J.A.A., M.S., I.S., I.W., D.F.); Involved in collection of data (D.A.H., J.A.A., I.W., M.S., I.S.); and involved in management, statistical analysis and interpretation of the data, and preparation of the manuscript (D.A.H., J.A.A., M.S., I.S.).
PY - 2006/12
Y1 - 2006/12
N2 - Purpose: To determine whether there is a correlation among mutations in the cytochrome P4501B1 gene (CYP1B1), the degree of angle dysgenesis observed histologically, and disease severity in congenital glaucoma. Design: Interventional case series. Methods: Direct DNA sequencing was used to screen six unrelated children with congenital glaucoma, each set of parents, and all siblings for CYP1B1 mutations. Specimens of the anterior chamber angle obtained at trabeculectomy were examined histologically to identify abnormalities of the aqueous outflow pathway. CYP1B1 mutations were correlated with both the degree of angle dysgenesis and the patients' disease severity (age at diagnosis, difficulty in achieving intraocular pressure [IOP]) control. Results: Four (66.7%) of the six patients were compound heterozygotes for mutations in the CYP1B1 gene. Seven of the eight CYP1B1 mutations were identified, including two novel mutations (R117P, C209R) and five others previously described (G61E, R368H, R390H, E229K, 4340delG). The cases were divided on the basis of histological phenotype into categories of (1) severe goniodysgenesis highlighted by the agenesis of the canal of Schlemm (two patients), (2) moderate goniodysgenesis characterized by the presence of a band of collagenous tissue (CT) in the trabecular meshwork (TM) and/or the juxtacanalicular tissues (JXT) (three patients), and (3) mild goniodysgenesis with deposition of a mucopolysaccharide material in the JXT (one patient). CYP1B1 mutations were identified in both cases of severe angle dysgenesis and two of three cases of moderate dysgenesis. Disease severity closely correlated with the degree of angle dysgenesis. Conclusions: Most patients in our cohort had compound heterozygous CYP1B1 mutations. Specific CYP1B1 mutations may be associated with severe or moderate angle abnormalities.
AB - Purpose: To determine whether there is a correlation among mutations in the cytochrome P4501B1 gene (CYP1B1), the degree of angle dysgenesis observed histologically, and disease severity in congenital glaucoma. Design: Interventional case series. Methods: Direct DNA sequencing was used to screen six unrelated children with congenital glaucoma, each set of parents, and all siblings for CYP1B1 mutations. Specimens of the anterior chamber angle obtained at trabeculectomy were examined histologically to identify abnormalities of the aqueous outflow pathway. CYP1B1 mutations were correlated with both the degree of angle dysgenesis and the patients' disease severity (age at diagnosis, difficulty in achieving intraocular pressure [IOP]) control. Results: Four (66.7%) of the six patients were compound heterozygotes for mutations in the CYP1B1 gene. Seven of the eight CYP1B1 mutations were identified, including two novel mutations (R117P, C209R) and five others previously described (G61E, R368H, R390H, E229K, 4340delG). The cases were divided on the basis of histological phenotype into categories of (1) severe goniodysgenesis highlighted by the agenesis of the canal of Schlemm (two patients), (2) moderate goniodysgenesis characterized by the presence of a band of collagenous tissue (CT) in the trabecular meshwork (TM) and/or the juxtacanalicular tissues (JXT) (three patients), and (3) mild goniodysgenesis with deposition of a mucopolysaccharide material in the JXT (one patient). CYP1B1 mutations were identified in both cases of severe angle dysgenesis and two of three cases of moderate dysgenesis. Disease severity closely correlated with the degree of angle dysgenesis. Conclusions: Most patients in our cohort had compound heterozygous CYP1B1 mutations. Specific CYP1B1 mutations may be associated with severe or moderate angle abnormalities.
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U2 - 10.1016/j.ajo.2006.07.054
DO - 10.1016/j.ajo.2006.07.054
M3 - Article
C2 - 17157584
AN - SCOPUS:33845186799
SN - 0002-9394
VL - 142
SP - 993-1004.e2
JO - American journal of ophthalmology
JF - American journal of ophthalmology
IS - 6
ER -