The Genetic Characteristics in South Korean Patients With Primary Congenital Glaucoma

Study of Gene, Inheritance Pattern and Genotype - Phenotype Correlations in South Korean Patients With Primary Congenital Glaucoma

Primary congenital glaucoma, which presents at birth or in infancy, if left untreated, may threaten vision. The incidence of congenital glaucoma varies among different geographic locations and ethnic groups.

Three genetic loci for primary congenital glaucoma (GLC3A in 2p21, GLC3B in 1p36, GLC3C in 14q24.3) were identified. CYP1B1 (cytochrome P450 1B1 ) gene, in the GLC3A locus is the main known gene and different CYP1B1 mutations has been described.

The genetic characteristics in south Korean patients with primary congenital glaucoma have not been reported yet and the genotype-phenotype correlations, the prognosis and the genetic counseling have not also been established. This study represents the first repot about the rate of CYP1B1 mutations, the genotype-phenotype correlations in south Korean patients with primary congenital glaucoma.

Patients with primary congenital glaucoma and their family will be analyzed for CYP1B1 mutations by direct sequencing of polymerase chain reaction fragments. Primary congenital glaucoma will be diagnosed according to the clinical parameters by glaucoma specialists. Patients were classified to several groups according to the pattern of mutations. Clinical parameters and genotype correlation will be compared between groups

Study Overview

• Status: Unknown
• Conditions: Primary Congenital Glaucoma

Detailed Description

The incidence of congenital glaucoma varies among different geographic locations and ethnic group. The incidence of primary congenital glaucoma is supposed to be 0.01-0.03% in Western countries but it is reported higher in the Middle East. The inheritance pattern for congenital glaucoma is most commonly autosomal recessive. But the fact that sex distribution is unequal and the reduced penetration is seen in patients with family history implies that it's inheritance pattern is unclear. Approximately 10-40% patients have family background and the rate of penetration is known to about 10-40%.

Linkage studies have been genetic heterogeneity and have mapped three loci for primary congenital glaucoma (GLC3A in 2p21, GLC3B in 1p36, GLC3C in 14q24.3). Molecular screening of the gene or primary congenital glaucoma families liked to the 2p21 locus has determined that mutations in the cytochrome P450 1B1 (CYP1B1)are responsible for phenotype.

The genetic characteristics in south Korean patients with primary congenital glaucoma have not been not reported yet and the genotype-phenotype correlations, prognosis, genetic counseling have not established. So In this study, we evaluate the rate of CYP1B1 mutations in south Korean patients with primary congenital glaucoma and establish genotype-phenotype correlations.

Patients with primary congenital glaucoma and their family will be analyzed for CYP1B1 mutations by direct sequencing of polymerase chain reaction fragments. 100 ethnically matched normal individuals served as control subjects. Primary congenital glaucoma will be determined by examinations with slit lamp biomicroscopy, gonioscopy, measurement of intraocular pressure, corneal diameter and axial length, optic disc evaluation by glaucoma specialists. Patients were classified to several groups according to the pattern of mutations. Clinical parameters and genotype correlation will be compared between groups.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Chang Won Kee, M.D., Ph.D.; Phone Number: 82-2-3410-3564; Email: ckee@skku.edu
• Study Contact Backup: Name: Sung Chul Park, M.D.; Phone Number: 82-2-3410-2320; Email: being111@hotmail.com

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 135-710
    • Recruiting
    • Samsung Medical Center
    • Contact: Chang Won Kee, M.D., Ph.D.; Phone Number: 82-2-3410-3564; Email: ckee@skku.edu
    • Contact: Sung Chul Park, M.D.; Phone Number: 82-2-3410-2320; Email: being111@hotmail.com
    • Principal Investigator: Chang Won Kee, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with primary congenital glaucoma who visit the glaucoma clinic in south Korea

Description

Inclusion Criteria:

• Clinical diagnosis of primary congenital glaucoma
• Candidate for peripheral blood sampling

Exclusion Criteria:

• Congenital glaucoma which relates with other systemic disease

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Glaucoma; South korean patients with primary congenital glaucoma

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
clinical parameters of primary congenital glaucoma (age, onset time, symptom, intraocular pressure, corneal diameter, cup to disc ratio, axial length, treatment type)	March 2010

Secondary Outcome Measures

Outcome Measure	Time Frame
clinical parameters of primary congenital glaucoma (age, onset time, symptom, intraocular pressure, corneal diameter, cup to disc ratio, refraction, axial length, treatment type)	september, 2010

Collaborators and Investigators

• Sponsor: Samsung Medical Center
• Investigators: Principal Investigator: Chang Won Kee, M.D., Samsung Medical Center

Publications and helpful links

General Publications

• Sarfarazi M, Stoilov I. Molecular genetics of primary congenital glaucoma. Eye (Lond). 2000 Jun;14 ( Pt 3B):422-8. doi: 10.1038/eye.2000.126.
• Panicker SG, Mandal AK, Reddy AB, Gothwal VK, Hasnain SE. Correlations of genotype with phenotype in Indian patients with primary congenital glaucoma. Invest Ophthalmol Vis Sci. 2004 Apr;45(4):1149-56. doi: 10.1167/iovs.03-0404.
• Ho CL, Walton DS. Primary congenital glaucoma: 2004 update. J Pediatr Ophthalmol Strabismus. 2004 Sep-Oct;41(5):271-88; quiz 300-1. doi: 10.3928/01913913-20040901-11.
• Miller SJ. Genetic aspects of glaucoma. Trans Ophthalmol Soc U K (1962). 1966;86:425-34. No abstract available.
• Gencik A. Epidemiology and genetics of primary congenital glaucoma in Slovakia. Description of a form of primary congenital glaucoma in gypsies with autosomal-recessive inheritance and complete penetrance. Dev Ophthalmol. 1989;16:76-115.

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Anticipated): March 1, 2010
• Study Completion (Anticipated): September 1, 2010

Study Registration Dates

• First Submitted: November 22, 2009
• First Submitted That Met QC Criteria: November 23, 2009
• First Posted (Estimate): November 25, 2009

Study Record Updates

• Last Update Posted (Estimate): November 25, 2009
• Last Update Submitted That Met QC Criteria: November 23, 2009
• Last Verified: August 1, 2008

More Information

Terms related to this study

• Keywords: CYP1B1 gene
• Additional Relevant MeSH Terms: Eye Diseases; Congenital Abnormalities; Ocular Hypertension; Eye Abnormalities; Glaucoma, Open-Angle; Infant, Newborn, Diseases; Glaucoma; Hydrophthalmos
• Other Study ID Numbers: 2008-08-070