Abstract
Primary congenital glaucoma (PCG) is the most common childhood glaucoma affecting children from birth to age 3 years and is a major cause of blindness in this young population.
Mutations in the CYP1B1 gene, associated with GLC3 locus, have been found to cause PCG in children worldwide and are the dominant genetic cause for pediatric glaucoma in the Middle East and Central Europe. Our study in a small number of Indonesian and European PCG families supports the previous studies that reported mutations of the CYP1B1 gene being responsible for the PCG phenotype. A different pattern of CYP1B1 disease-causing mutations and benign variants appears to exist in Indonesian patients when compared to patients from other ethnic backgrounds.
Other genes such as LTBP2 and PXDN gene have been reported recently by several studies as being associated with pediatric glaucoma.
The exact mechanisms of how these gene abnormalities actually cause primary congenital glaucoma remain unclear. However, with the promising research progress so far, it is hoped that we will understand more about the pathogenesis of this disease and eventually potential new molecular targets to treat this threatening blindness disease in children will be developed in the near future.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Cascella R, Strafella C, Germani C, Novelli G, Ricci F, Zampatti S, et al. The Genetics and the Genomics of Primary Congenital Glaucoma [Internet]. BioMed Res Int. 2015 [cited 2017 Oct 18].
Sitorus RS, Abidin MS, Prihartono J. Causes and temporal trends of childhood blindness in Indonesia: study at schools for the blind in Java. Br J Ophthalmol. 2007 Sep;91(9):1109–13.
Bejjani BA, Lewis RA, Tomey KF, Anderson KL, Dueker DK, Jabak M, 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 Feb;62(2):325–33.
Abu-Amero KK, Osman EA, Mousa A, Wheeler J, Whigham B, Allingham RR, et al. Screening of CYP1B1 and LTBP2 genes in Saudi families with primary congenital glaucoma: genotype-phenotype correlation. Mol Vis. 2011;17:2911–9.
Rauf B, Irum B, Kabir F, Firasat S, Naeem MA, Khan SN, et al. A spectrum of CYP1B1 mutations associated with primary congenital glaucoma in families of Pakistani descent. Hum Genome Var. 2016;3:hgv201621.
Sarfarazi M, Stoilov I. Molecular genetics of primary congenital glaucoma. Eye. 2000 May;14(3b):422–8.
Friedman JS, Ma W. Glaucoma genetics present and future. Clin Genet. 1999;55:71–9.
Stoilov IR, Sarfarazi M. The third genetic locus (GLC3C) for primary congenital glaucoma (PCG) maps to chromosome 14q24.3. Fort Lauderdale: Association for Research in Vision and Ophthalmology; 2002.
Tang YM, Wo YY, Stewart J, Hawkins AL, Griffin CA, Sutter TR, et al. Isolation and characterization of the human cytochrome P450 CYP1B1 gene. J Biol Chem. 1996;271:28324–30.
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;36:290–4.
Sitorus R, Ardjo SM, Lorenz B, Preising M. CYP1B1 gene analysis in primary congenital glaucoma in Indonesian and European patients. J Med Genet. 2003;40(1):9e–9.
Stoilov I, Akarsu AN, Alozie I, Child A, Barsoum-Homsy M, Turacli ME, 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;62:573–84.
Vincent A, Billingsley G, Priston M, Williams-Lyn D, Sutherland J, Glaser T, et al. Phenotypic heterogeneity of CYP1B1: mutations in a patient with Peters’ anomaly. J Med Genet. 2001;38:324–6.
Vincent AL, Billingsley GD, Priston MK, Williams-Lyn D, Sutherland J, Glaser T, et al. Phenotypic heterogeneity of CYP1B1 suggested by mutations in a patient with Peters’ anomaly. Am J Hum Genet. 2000;67:411.
Stoilov IR, Costa VP, Vasconcellos JP, Melo MB, Betinjane AJ, Carani JC, et al. Molecular genetics of primary congenital glaucoma in Brazil. Invest Ophthalmol Vis Sci. 2002;43:1820–7.
McLellan RA, Oscarson M, Hidestrand M, Leidvik B, Jonsson E, Otter C, et al. Characterization and functional analysis of two common human cytochrome P450 1B1 variants. Arch Biochem Biophys. 2000;378:175–81.
Mashima Y, Suzuki Y, Sergeev Y, Ohtake Y, Tanino T, Kimura I, et al. Novel cytochrome P4501B1 (CYP1B1) gene mutations in Japanese patients with primary congenital glaucoma. Invest Ophthalmol Vis Sci. 2001;42:2211–6.
Sutter TR, Tang YM, Hayes CL, Wo YY, Jabs EW, Li X, 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;269:13092–9.
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;6:641–7.
Yosra B, Salim BY, Nesrine A, Rim K, Rym K, Moncef K, et al. CYP1B1 gene mutations causing primary congenital glaucoma in Tunisia. Ann Hum Genet. 2014;78(4):255–63.
Lim S-H, Tran-Viet K-N, Yanovitch TL, Freedman SF, Klemm T, Call W, et al. CYP1B1, MYOC, and LTBP2 mutations in primary congenital glaucoma patients in the United States. Am J Ophthalmol. 2013;155(3):508–517.e5.
Millá E, Mañé B, Duch S, Hernan I, Borràs E, Planas E, et al. Survey of familial glaucoma shows a high incidence of cytochrome P450, family 1, subfamily B, polypeptide 1 (CYP1B1) mutations in non-consanguineous congenital forms in a Spanish population. Mol Vis. 2013;19:1707–22.
Kim H-J, Suh W, Park SC, Kim CY, Park KH, Kook MS, et al. Mutation spectrum of CYP1B1 and MYOC genes in Korean patients with primary congenital glaucoma. Mol Vis. 2011;17:2093–101.
Hilal L, Boutayeb S, Serrou A, Refass-Buret L, Shisseh H, Bencherifa F, et al. Screening of CYP1B1 and MYOC in Moroccan families with primary congenital glaucoma: three novel mutations in CYP1B1. Mol Vis. 2010 Jul 2;16:1215–26.
Campos-Mollo E, López-Garrido M-P, Blanco-Marchite C, Garcia-Feijoo J, Peralta J, Belmonte-Martínez J, et al. CYP1B1 mutations in Spanish patients with primary congenital glaucoma: phenotypic and functional variability. Mol Vis. 2009;15:417–31.
Chen Y, Jiang D, Yu L, Katz B, Zhang K, Wan B, et al. CYP1B1 and MYOC mutations in 116 Chinese patients with primary congenital glaucoma. Arch Ophthalmol Chic Ill. 2008;126(10):1443–7.
El-Ashry MF, Abd El-Aziz MM, Bhattacharya SS. A clinical and molecular genetic study of Egyptian and Saudi Arabian patients with primary congenital glaucoma (PCG). J Glaucoma. 2007 Jan;16(1):104–11.
Zhao Y, Sorenson CM, Sheibani N. Cytochrome P450 1B1 and primary congenital Glaucoma. J Ophthalmic Vis Res. 2015;10(1):60–7.
Micheal S, Siddiqui SN, Zafar SN, Iqbal A, Khan MI, den Hollander AI. Identification of novel variants in LTBP2 and PXDN using whole-exome sequencing in developmental and congenital glaucoma. PLoS One. 2016;11(7):e0159259.
Acknowledgments
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Ethics declarations
The author declares that this manuscript is written in accordance with the ethical standards and comply with the ethical requirements.
In this manuscript, permission from the copyright holder (BMJ Publishing Group Ltd.) has been taken for the excerpts from copyrighted works such as illustrations, tables, animations, or text quotations included.
Rights and permissions
Copyright information
© 2019 Springer Nature Singapore Pte Ltd.
About this chapter
Cite this chapter
Sitorus, R.S. (2019). CYP1B1 Gene Mutation in Primary Congenital Glaucoma. In: Prakash, G., Iwata, T. (eds) Advances in Vision Research, Volume II. Essentials in Ophthalmology. Springer, Singapore. https://doi.org/10.1007/978-981-13-0884-0_27
Download citation
DOI: https://doi.org/10.1007/978-981-13-0884-0_27
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-13-0883-3
Online ISBN: 978-981-13-0884-0
eBook Packages: MedicineMedicine (R0)