Screening glaucoma genes in adult glaucoma suggests a multiallelic contribution of CYP1B1 to open-angle glaucoma phenotypes - PubMed (original) (raw)
Screening glaucoma genes in adult glaucoma suggests a multiallelic contribution of CYP1B1 to open-angle glaucoma phenotypes
Hussain Y Patel et al. Clin Exp Ophthalmol. 2012 May-Jun.
Abstract
Background: Despite increasing knowledge of the genetic pathophysiology of glaucoma, mutations in known genes account for less than 15% of disease. Gene screening predominantly remains a research tool rather than an essential part of the clinical work-up. We aimed to determine the mutational spectrum and frequency in the genes implicated in glaucoma, in a range of glaucoma and 'glaucoma suspect' (GS) participants, with a positive family history.
Methods: Observational large case series. One hundred fifteen patients recruited from public hospital and private clinics had diagnoses of GS, ocular hypertension, pseudoexfoliative glaucoma (PXG) or primary open-angle glaucoma (POAG), and at least one affected family member. In a university laboratory, DNA samples were screened for mutations in all coding exons of MYOC and CYP1B1, and OPTN (exons 4, 5 and 16). WDR36 (exons 1, 4, 5, 8, 11, 13 and 17) was screened in those with CYP1B1 changes. LOXL1 risk variants were screened in PXG pedigrees. Cascade screening of family members was undertaken.
Results: Seven out of one hundred fifteen (6.1%) individuals had at least one pathogenic or hypomorphic CYP1B1 allele associated with GS, POAG (5) and PXG phenotypes, including two novel sequence variations (p.Ser6Gly, p.Val243Leu). No pathogenic MYOC change was detected. Five individuals (4.3%) carried an OPTN sequence variation. Three of the seven with CYP1B1 changes had polygenic changes.
Conclusions: Mutational analysis of known glaucoma genes in a mixed glaucoma population replicates the reported frequency of pathogenic CYP1B1 changes. Heterozygous CYP1B1 changes occurred at a greater frequency than other genes. Glaucoma pathogenesis in the clinic setting is genetically heterogeneous and may be polygenic.
© 2011 The Authors. Clinical and Experimental Ophthalmology © 2011 Royal Australian and New Zealand College of Ophthalmologists.
Similar articles
- Role of CYP1B1, MYOC, OPTN, and OPTC genes in adult-onset primary open-angle glaucoma: predominance of CYP1B1 mutations in Indian patients.
Kumar A, Basavaraj MG, Gupta SK, Qamar I, Ali AM, Bajaj V, Ramesh TK, Prakash DR, Shetty JS, Dorairaj SK. Kumar A, et al. Mol Vis. 2007 Apr 30;13:667-76. Mol Vis. 2007. PMID: 17563717 Free PMC article. - Correction of the disease phenotype of myocilin-causing glaucoma by a natural osmolyte.
Jia LY, Gong B, Pang CP, Huang Y, Lam DS, Wang N, Yam GH. Jia LY, et al. Invest Ophthalmol Vis Sci. 2009 Aug;50(8):3743-9. doi: 10.1167/iovs.08-3151. Epub 2009 Feb 21. Invest Ophthalmol Vis Sci. 2009. PMID: 19234343 - Genetics of primary glaucoma.
Khan AO. Khan AO. Curr Opin Ophthalmol. 2011 Sep;22(5):347-55. doi: 10.1097/ICU.0b013e32834922d2. Curr Opin Ophthalmol. 2011. PMID: 21730848 Review. - SNPs and interaction analyses of myocilin, optineurin, and apolipoprotein E in primary open angle glaucoma patients.
Fan BJ, Wang DY, Fan DS, Tam PO, Lam DS, Tham CC, Lam CY, Lau TC, Pang CP. Fan BJ, et al. Mol Vis. 2005 Aug 29;11:625-31. Mol Vis. 2005. PMID: 16148883 - [From gene to disease; primary open-angle glaucoma and three known genes: MYOC, CYP1B1 and OPTN].
Bergen AA, Leschot NJ, Hulsman CA, De Smet MD, De Jong PT. Bergen AA, et al. Ned Tijdschr Geneeskd. 2004 Jul 3;148(27):1343-4. Ned Tijdschr Geneeskd. 2004. PMID: 15283026 Review. Dutch.
Cited by
- Loss of optineurin in vivo results in elevated cell death and alters axonal trafficking dynamics.
Paulus JD, Link BA. Paulus JD, et al. PLoS One. 2014 Oct 16;9(10):e109922. doi: 10.1371/journal.pone.0109922. eCollection 2014. PLoS One. 2014. PMID: 25329564 Free PMC article. - Analysis of CYP1B1 in pediatric and adult glaucoma and other ocular phenotypes.
Reis LM, Tyler RC, Weh E, Hendee KE, Kariminejad A, Abdul-Rahman O, Ben-Omran T, Manning MA, Yesilyurt A, McCarty CA, Kitchner TE, Costakos D, Semina EV. Reis LM, et al. Mol Vis. 2016 Oct 17;22:1229-1238. eCollection 2016. Mol Vis. 2016. PMID: 27777502 Free PMC article. - Association of WDR36 polymorphisms with primary open angle glaucoma: A systematic review and meta-analysis.
Liu K, He W, Zhao J, Zeng Y, Cheng H. Liu K, et al. Medicine (Baltimore). 2017 Jun;96(26):e7291. doi: 10.1097/MD.0000000000007291. Medicine (Baltimore). 2017. PMID: 28658128 Free PMC article. Review. - Association of a polymorphism in the BIRC6 gene with pseudoexfoliative glaucoma.
Ayub H, Micheal S, Akhtar F, Khan MI, Bashir S, Waheed NK, Ali M, Schoenmaker-Koller FE, Shafique S, Qamar R, Hollander AI. Ayub H, et al. PLoS One. 2014 Aug 13;9(8):e105023. doi: 10.1371/journal.pone.0105023. eCollection 2014. PLoS One. 2014. PMID: 25118708 Free PMC article. - Next-generation sequencing-based gene panel tests for the detection of rare variants and hypomorphic alleles associated with primary open-angle glaucoma.
Milla E, Laguna J, Alforja MS, Pascual B, Gamundi MJ, Borràs E, Hernán I, Muniesa MJ, Pazos M, Duch S, Carballo M, Jodar M; EMEIGG group. Milla E, et al. PLoS One. 2024 Jan 19;19(1):e0282133. doi: 10.1371/journal.pone.0282133. eCollection 2024. PLoS One. 2024. PMID: 38241218 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources