Original articleCytochrome P450 1B1 gene mutations in Japanese patients with primary congenital glaucoma1☆,
Section snippets
Patients
Eleven patients were diagnosed with primary congenital glaucoma and followed up between 1979 and 1998 in the Kagoshima University Medical Center, a tertiary referral institution in the Kagoshima prefecture of southwestern Japan with an average annual new birth rate of approximately 17,000 during the study period.
The clinical information of the patients is summarized in Table 1. Each patient belonged to unrelated families who had resided in the Kagoshima prefecture; 10 patients were sporadic and
Disease-causative mutations
One patient (Case 1) showed a novel mutation in the CYP1B1 gene that is responsible for primary congenital glaucoma. This mutation consisted of an alteration of nucleotide 1677 from guanine to adenine that resulted in amino acid substitution from arginine to glutamine at codon 444 (R444Q) in exon 3 (Figure 1). Taq I–restriction detection revealed that the patient had homozygous mutant alleles and that the family members were either heterozygous with mutant and wild-type allele or homozygous
Case 1
A 6-year-old Japanese female (Table 1), who was found to have the R444Q mutation, was referred by a local doctor for ophthalmologic studies because, although she had been visually asymptomatic with normal physical and mental developments, she was found at the preschool vision check-up to have unsatisfactory vision in the right eye. Her parents were first cousins but were healthy, and there was no contributory family history. On examination, best visual acuity was 0.6 in RE and 1.2 in LE.
Discussion
Previous studies reported a wide range of mutations in the coding regions of the CYP1B1 gene in patients with primary congenital glaucoma. The current Human Gene Mutation Database Cardiff compiles a total of 22 mutations of the gene among patients in the Mid East and Western countries, consisting of 13 missense or nonsense amino acid substitutions, four small deletions, three small insertions, and two gross abnormalities. 10
These mutations were homozygous or compound heterozygous in affected
References (13)
- et al.
Assignment of a locus (GLC3A) for primary congenital glaucoma (Buphthalmos) to 2p21 and evidence for genetic heterogeneity
Genomics
(1995) - et al.
Sequence analysis and homology modeling suggest that primary congenital glaucoma on 2p21 results from mutations disrupting either the hinge region or the conserved core structures of cytochrome P4501B1
Am J Hum Genet
(1998) - et al.
Mutations in CYP1B1, the gene for cytochrome P4501B1, are the predominant cause of primary congenital glaucoma in Saudi Arabia
Am J Hum Genet
(1998) - et al.
A novel truncating mutation of cytochrome P4501B1 (CYP1B1) gene in primary infantile glaucoma
Am J Ophthalmol
(1999) - et al.
Complete cDNA sequence of a human dioxin-inducible mRNA identifies a new gene subfamily of cytochrome P450 that maps to chromosome 2
J Biol Chem
(1994) - et al.
Isolation and characterization of the human cytochrome P450 CYP1B1 gene
J Biol Chem
(1996)
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This work was supported by Grants-in-Aid for Scientific Research (12877279, 12671715) from the Japanese Ministry of Education, Science and Culture, Tokyo, Japan.
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No proprietary interest.