Original articleCytochrome P450 1B1 gene mutations in Japanese patients with primary congenital glaucoma1☆,
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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
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Cited by (57)
Childhood Glaucomas
2015, Glaucoma: Second EditionOverview of Cytochrome P450 1B1 gene mutations in patients with primary congenital glaucoma
2011, Experimental Eye ResearchCitation Excerpt :Finally, DNA mutations within the CYP1B1 gene were identified in 542 patients with PCG reported in 52 scientific articles. Table 1 showed the studies included in the overview (Alfadhli et al., 2006; Bagiyeva et al., 2007; Bar-Yosef et al., 2010; Bejjani et al., 1998, 2000; Belmouden et al., 2002; Brinkmann et al., 2006a, b; Campos-Mollo et al., 2009; Chakrabarti et al., 2003; Chavarria-Soley et al., 2006; Chen et al., 2008; Chitsazian et al., 2007; Colomb et al., 2003; Curry et al., 2004; Della Paolera et al., 2010; Dimasi et al., 2007; El-Ashry et al., 2007; El-Gayar et al., 2009; Firasat et al., 2008; Fuse et al., 2010; Hilal et al., 2010; Hollander et al., 2006; Huang et al., 2009; Huang et al., 2007; Jiang et al., 2007; Kakiuchi-Matsumoto et al., 2001; Lopez-Garrido et al., 2009; Martin et al., 2000; Mashima et al., 2001; Messina-Baas et al., 2007; Michels-Rautenstrauss et al., 2001; Nirmaladevi et al., 2006a, b; Panicker et al., 2004; Plasilova et al., 1999; Ramprasad et al., 2007; Reddy et al., 2004, 2003; Sena et al., 2004; Sitorus et al., 2003; Sivadorai et al., 2008; Stoilov et al., 1998, 1997, 2002; Strom et al., 2006; Suri et al., 2009; Tanwar et al., 2009a, 2009b; Weisschuh et al., 2009; Yang et al., 2009; Zenteno et al., 2008). Altogether, 147 distinct mutations were observed in 542 patients.
A Clinical and Molecular Genetic Study of German Patients with Primary Congenital Glaucoma
2009, American Journal of OphthalmologyMeta-analysis of CYP1B1 gene mutations in primary congenital glaucoma patients
2021, European Journal of Ophthalmology
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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.