Skip to main content

Advertisement

SpringerLink
Log in

Mutation spectrum of the CYP1B1 gene for congenital glaucoma in the Japanese population

  • Clinical Investigation
  • Published:
Japanese Journal of Ophthalmology Aims and scope Submit manuscript

Abstract

Purpose

Mutations of the CYP1B1 gene cause primary congenital glaucoma (PCG), Peters anomaly, and juvenile open-angle glaucoma (JOAG). The aim of this study was to determine the spectrum and role of the CYP1B1 gene in Japanese patients with PCG or JOAG.

Methods

Genomic DNA was extracted from the leukocytes of 18 unrelated patients with PCG and 21 unrelated patients with JOAG. All of the patients developed high intraocular pressure (IOP) before the age of 35 years. One hundred unrelated healthy adults with normal IOP were examined in the same way. The three exons of the CYP1B1 gene were amplified by polymerase chain reaction and directly sequenced.

Results

Mutational screening and sequence analyses of the CYP1B1 gene revealed four mutations in four patients with PCG: p.Asp192Val, c.4776insAT, p.Val364Met, and p.Asp430Glu. The first three mutations have been reported in other Japanese PCG patients, but Asp430Glu is a new mutation. No mutations were found in the CYP1B1 gene of the JOAG patients.

Conclusions

PCG in approximately 20% of Japanese patients may be associated with CYP1B1 mutations, but JOAG is not. The three mutations p.Asp192Val, c.4776insAT, and p.Val364Met appear to be common in the Japanese population and might be useful in genetic screening for PCG.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Sarfarazi M, Akarsu AN, Hossain A, et al. Assignment of a locus (GLC3A) for primary congenital glaucoma (buphthalmos) to 2p21 and evidence for genetic heterogeneity. Genomics 1995;30:171–177.

    Article  CAS  PubMed  Google Scholar 

  2. Akarsu AN, Turacli ME, Aktan SG, et al. A second locus (GLC3B) for primary congenital glaucoma (buphthalmos) maps to the 1p36 region. Hum Mol Genet 1996;5:1199–1203.

    Article  CAS  PubMed  Google Scholar 

  3. Stoilov I, Sarfarazi M. Invest Ophthalmol Vis Sci 2002;43:EAbstract 3015;gene ID399565.

  4. Stoilov I, Akarsu AN, Sarfarazi M. Identification of three different truncating mutations in cytochrome P4501B1 (CYP1B1) as the principal cause of primary congenital glaucoma (buphthalmos) in families linked to the GLC3A locus on chromosome 2p21. Hum Mol Genet 1997;6:641–647.

    Article  CAS  PubMed  Google Scholar 

  5. Stoilov I, Jansson I, Sarfarazi M, Schenkman JB. Roles of cytochrome p450 in development. Drug Metab Drug Interact 2001;18:33–55.

    CAS  Google Scholar 

  6. Stoilov I, Akarsu AN, Alozie I, 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;62:573–584.

    Article  CAS  PubMed  Google Scholar 

  7. Plasilova M, Stoilov I, Sarfarazi M, Kadasi L, Ferakova E, Ferak V. Identification of a single ancestral CYP1B1 mutation in Slovak Gypsies (Roms) affected with primary congenital glaucoma. J Med Genet 1999;36:290–294.

    CAS  PubMed  Google Scholar 

  8. Bejjani BA, Stockton DW, Lewis RA, et al. Multiple CYP1B1 mutations and incomplete penetrance in an inbred population segregating primary congenital glaucoma suggest frequent de novo events and a dominant modifier locus. Hum Mol Genet 2000;9:367–374.

    Article  CAS  PubMed  Google Scholar 

  9. Martin SN, Sutherland J, Levin AV, Klose R, Priston M, Heon E. Molecular characterisation of congenital glaucoma in a consanguineous Canadian community: a step towards preventing glaucoma related blindness. J Med Genet 2000;37:422–427.

    Article  CAS  PubMed  Google Scholar 

  10. Michels-Rautenstrauss KG, Mardin CY, Zenker M, Jordan N, Gusek-Schneider GC, Rautenstrauss BW. Primary congenital glaucoma: three case reports on novel mutations and combinations of mutations in the GLC3A (CYP1B1) gene. J Glaucoma 2001;10:354–357.

    Article  CAS  PubMed  Google Scholar 

  11. Stoilov IR, Costa VP, Vasconcellos JP, et al. Molecular genetics of primary congenital glaucoma in Brazil. Invest Ophthalmol Vis Sci 2002;43:1820–1827.

    PubMed  Google Scholar 

  12. Belmouden A, Melki R, Hamdani M, et al. A novel frameshift founder mutation in the cytochrome P450 1B1 (CYP1B1) gene is associated with primary congenital glaucoma in Morocco. Clin Genet 2002;62:334–339.

    Article  CAS  PubMed  Google Scholar 

  13. Panicker SG, Reddy AB, Mandal AK, et al. Identification of novel mutations causing familial primary congenital glaucoma in Indian pedigrees. Invest Ophthalmol Vis Sci 2002;43:1358–1366.

    PubMed  Google Scholar 

  14. Reddy AB, Panicker SG, Mandal AK, Hasnain SE, Balasubramanian D. Identification of R368H as a predominant CYP1B1 allele causing primary congenital glaucoma in Indian patients. Invest Ophthalmol Vis Sci 2003;44:4200–4203.

    Article  PubMed  Google Scholar 

  15. Colomb E, Kaplan J, Garchon HJ. Novel cytochrome P450 1B1 (CYP1B1) mutations in patients with primary congenital glaucoma in France. Hum Mutat 2003;22:496.

    Article  PubMed  Google Scholar 

  16. Soley GC, Bosse KA, Flikier D, et al. Primary congenital glaucoma: a novel single-nucleotide deletion and varying phenotypic expression for the 1,546–1,555dup mutation in the GLC3A (CYP1B1) gene in 2 families of different ethnic origin. J Glaucoma 2003;12:27–30.

    Article  PubMed  Google Scholar 

  17. Melki R, Colomb E, Lefort N, Brezin AP, Garchon HJ. CYP1B1 mutations in French patients with early-onset primary open-angle glaucoma. J Med Genet 2004;41:647–651.

    Article  CAS  PubMed  Google Scholar 

  18. Sena DF, Finzi S, Rodgers K, Del Bono E, Haines JL, Wiggs JL. Founder mutations of CYP1B1 gene in patients with congenital glaucoma from the United States and Brazil. J Med Genet 2004;41:e6.

    Article  CAS  PubMed  Google Scholar 

  19. Kakiuchi T, Isashiki Y, Nakao K, Sonoda S, Kimura K, Ohba N. A novel truncating mutation of cytochrome P4501B1 (CYP1B1) gene in primary infantile glaucoma. Am J Ophthalmol 1999;128:370–372.

    Article  CAS  PubMed  Google Scholar 

  20. Ohtake Y, Kubota R, Tanino T, Miyata H, Mashima Y. Novel compound heterozygous mutations in the cytochrome P4501B1 gene (CYP1B1) in a Japanese patient with primary congenital glaucoma. Ophthalmic Genet 2000;21:191–193.

    CAS  PubMed  Google Scholar 

  21. Kakiuchi-Matsumoto T, Isashiki Y, Ohba N, Kimura K, Sonoda S, Unoki K. Cytochrome P450 1B1 gene mutations in Japanese patients with primary congenital glaucoma (1). Am J Ophthalmol 2001;131:345–350.

    Article  CAS  PubMed  Google Scholar 

  22. Mashima Y, Suzuki Y, Sergeev Y, et al. Novel cytochrome P4501B1 (CYP1B1) gene mutations in Japanese patients with primary congenital glaucoma. Invest Ophthalmol Vis Sci 2001;42:2211–2216.

    CAS  PubMed  Google Scholar 

  23. Bejjani BA, Lewis RA, Tomey KF, 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;62:325–333.

    Article  CAS  PubMed  Google Scholar 

  24. Acharya M, Mookherjee S, Bhattacharjee A, et al. Primary role of CYP1B1 in Indian juvenile-onset POAG patients. Mol Vis 2006;12:399–404.

    CAS  PubMed  Google Scholar 

  25. Churchill AJ, Yeung A. A compound heterozygous change found in Peters’ anomaly. Mol Vis 2005;11:66–70.

    CAS  PubMed  Google Scholar 

  26. Edward D, Al Rajhi A, Lewis RA, Curry S, Wang Z, Bejjani B. Molecular basis of Peters anomaly in Saudi Arabia. Ophthalmic Genet 2004;25:257–270.

    Article  CAS  PubMed  Google Scholar 

  27. Vincent A, Billingsley G, Priston M, et al. Phenotypic heterogeneity of CYP1B1: mutations in a patient with Peters’ anomaly. J Med Genet 2001;38:324–326.

    Article  CAS  PubMed  Google Scholar 

  28. Vincent A, Billingsley G, Priston M, et al. Further support of the role of CYP1B1 in patients with Peters anomaly. Mol Vis 2006;12:506–510.

    CAS  PubMed  Google Scholar 

  29. Vincent AL, Billingsley G, Buys Y, et al. Digenic inheritance of early-onset glaucoma: CYP1B1, a potential modifier gene. Am J Hum Genet 2002;70:448–460.

    Article  CAS  PubMed  Google Scholar 

  30. Chen Y, Jiang D, Yu L, et al. CYP1B1 and MYOC mutations in 116 Chinese patients with primary congenital glaucoma. Arch Ophthalmol 2008;126:1443–1447

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Ophthalmology and Visual Sciences, Tohoku University Graduate School of Medicine, Sendai, Japan

    Nobuo Fuse, Akiko Miyazawa, Toru Nakazawa & Kohji Nishida

  2. Hiraka General Hospital, Yokote, Japan

    Kana Takahashi

  3. Sendai Medical Center, Sendai, Japan

    Michiru Noro

  4. Department of Ophthalmology and Visual Sciences, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan

    Nobuo Fuse

Authors
  1. Nobuo Fuse
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Akiko Miyazawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kana Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michiru Noro
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Toru Nakazawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kohji Nishida
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nobuo Fuse.

About this article

Cite this article

Fuse, N., Miyazawa, A., Takahashi, K. et al. Mutation spectrum of the CYP1B1 gene for congenital glaucoma in the Japanese population. Jpn J Ophthalmol 54, 1–6 (2010). https://doi.org/10.1007/s10384-009-0769-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10384-009-0769-1

Keywords

Search

Navigation