Original article
Cytochrome P450 1B1 gene mutations in Japanese patients with primary congenital glaucoma1,

https://doi.org/10.1016/S0002-9394(00)00808-4Get rights and content

Abstract

PURPOSE: To report a novel missense mutation and DNA polymorphism of the CYP1B1gene in Japanese patients with primary congenital glaucoma.

METHODS: A series of 11 unrelated patients with primary congenital glaucoma was examined. Patients were followed in the Kagoshima University Hospital between 1979 and 1998. DNA was extracted from leukocytes of the patients, their families, and unrelated healthy individuals. Amplicons spanning the coding regions of the CYP1B1 gene were examined by direct sequencing and enzyme-restriction detection.

RESULTS: In the 11 unrelated patients, besides the previously reported insertional mutation (1620 ins G), a novel missense mutation was identified at codons 444 to replace arginine with glutamine (R444Q) in one patient. The novel missense mutation cosegregated in the relevant family as an autosomal recessive pattern and was not found in other patients or control individuals. In addition, five polymorphic sites were found at codons 48, 119, 330, 432, and 449. These polymorphic alleles did not cosegregate with the disease, and they were found in healthy individuals as well.

CONCLUSIONS: Approximately 20% of Japanese patients with primary congenital glaucoma may be affected by mutations in the CYP1B1 gene. Further studies are justified to explore whether a relationship exists between the phenotypic expressivity of the disease and the type of mutation.

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

Cited by (0)

This work was supported by Grants-in-Aid for Scientific Research (12877279, 12671715) from the Japanese Ministry of Education, Science and Culture, Tokyo, Japan.

1

No proprietary interest.

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