J Pediatr Genet 2024; 13(04): 277-282
DOI: 10.1055/s-0043-1774294
Original Article

CYP1B1 and MYOC Gene Analysis of Patients with Primary Congenital Glaucoma in the Cukurova Region of Türkiye

1   Ophthalmology Department, Seyhan State Hospital, Adana, Türkiye
,
2   Ophthalmology Department, Cukurova University Faculty of Medicine, Adana, Türkiye
,
3   Medical Genetics Department, Cukurova University Faculty of Medicine, Adana, Türkiye
,
2   Ophthalmology Department, Cukurova University Faculty of Medicine, Adana, Türkiye
,
2   Ophthalmology Department, Cukurova University Faculty of Medicine, Adana, Türkiye
› Author Affiliations
Funding None.

Abstract

The aim of this study was to investigate the CYP1B1 and MYOC genes in patients with primary congenital glaucoma (PCG) from the Cukurova region (located in the south of Türkiye) and reveal the relationship between gene mutations and clinical severity of the disease. Molecular genetic and clinical study was conducted in 42 eyes of 26 patients who were followed for a diagnosis of PCG. The clinical diagnosis was concluded by ophthalmological examination under general anesthesia or slit-lamp biomicroscopy, gonioscopy, and measurement of the intraocular pressure. A CYP1B1 gene mutation was detected in 12 patients (46.2%). Two of these patients had a combination of CYP1B1 and MYOC mutations. The most common pathogenic variant, c.1405C > T (p.R469W) (n = 5), was present in patients with mutations, and the prognosis was poor compared with other modifications (p = 0.014). The second most common variant was c.3987G > A (p.G61E) (n = 3), which was associated with a good prognosis. The incidence of buphthalmos and the mean horizontal corneal diameter were higher in patients with mutations in the CYP1B1 and MYOC genes. All parents were found to be carriers of the mutation gene. This is the report on molecular genetic analysis of PCG in the southern region of Türkiye. Some specific genetic variants may have an effect on the prognosis of the disease. However, patients without mutations in these case groups may have mutations in genes yet to be identified.



Publication History

Received: 31 January 2023

Accepted: 03 August 2023

Article published online:
06 September 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
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  • 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 (02) 171-177
  • 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 (08) 1199-1203
  • 3 Sarfarazi M, Stoilov I, Schenkman JB. Genetics and biochemistry of primary congenital glaucoma. Ophthalmol Clin North Am 2003; 16 (04) 543-554 , vi
  • 4 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 (03) 367-374
  • 5 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 (01) e6-e6
  • 6 Chen Y, Jiang D, Yu L. et al. CYP1B1 and MYOC mutations in 116 Chinese patients with primary congenital glaucoma. Arch Ophthalmol 2008; 126 (10) 1443-1447
  • 7 Coêlho REA, Sena DR, Santa Cruz F. et al. CYP1B1 gene and phenotypic correlation in patients from northeastern Brazil with primary congenital glaucoma. J Glaucoma 2019; 28 (02) 161-164
  • 8 Lundvall A, Svedberg H, Chen E. Application of the ICare rebound tonometer in healthy infants. J Glaucoma 2011; 20 (01) 7-9
  • 9 Fang L, Guo X, Yang Y. et al. Trabeculotomy versus combined trabeculotomy-trabeculectomy for primary congenital glaucoma: study protocol of a randomised controlled trial. BMJ Open 2020; 10 (02) e032957
  • 10 Plásilová M, Stoilov I, Sarfarazi M, Kádasi L, Feráková E, Ferák V. Identification of a single ancestral CYP1B1 mutation in Slovak Gypsies (Roms) affected with primary congenital glaucoma. J Med Genet 1999; 36 (04) 290-294
  • 11 Chang TC, Cavuoto KM. Surgical management in primary congenital glaucoma: four debates. J Ophthalmol 2013; 2013: 612708
  • 12 de Silva DJ, Khaw PT, Brookes JL. Long-term outcome of primary congenital glaucoma. J AAPOS 2011; 15 (02) 148-152
  • 13 Zhang L, Savas U, Alexander DL, Jefcoate CR. Characterization of the mouse Cyp1B1 gene. Identification of an enhancer region that directs aryl hydrocarbon receptor-mediated constitutive and induced expression. J Biol Chem 1998; 273 (09) 5174-5183
  • 14 Zhao Y, Sorenson CM, Sheibani N. Cytochrome P450 1B1 and primary congenital glaucoma. J Ophthalmic Vis Res 2015; 10 (01) 60-67
  • 15 Li N, Zhou Y, Du L, Wei M, Chen X. Overview of cytochrome P450 1B1 gene mutations in patients with primary congenital glaucoma. Exp Eye Res 2011; 93 (05) 572-579
  • 16 Do T, Shei W, Chau PTM. et al. vd. CYP1B1 and MYOC mutations in Vietnamese primary congenital glaucoma patients. J Glaucoma 2016; 25 (05) e491-e498
  • 17 Stoilov IR, Costa VP, Vasconcellos JP. et al. Molecular genetics of primary congenital glaucoma in Brazil. Invest Ophthalmol Vis Sci 2002; 43 (06) 1820-1827
  • 18 Benson MT, Nelson ME. Cyclocryotherapy: a review of cases over a 10-year period. Br J Ophthalmol 1990; 74 (02) 103-105
  • 19 Mikstacka R, Dutkiewicz Z. New perspectives of CYP1B1 inhibitors in the light of molecular studies. Processes (Basel) 2021; 9 (05) 817
  • 20 Lewis CJ, Hedberg-Buenz A, DeLuca AP, Stone EM, Alward WLM, Fingert JH. Primary congenital and developmental glaucomas. Hum Mol Genet 2017; 26 (R1): R28-R36
  • 21 Yang M, Guo X, Liu X. et al. Investigation of CYP1B1 mutations in Chinese patients with primary congenital glaucoma. Mol Vis 2009; 15: 432-437
  • 22 Ava S, Demirtaş AA, Karahan M, Erdem S, Oral D, Keklikçi U. Genetic analysis of patients with primary congenital glaucoma. Int Ophthalmol 2021; 41 (07) 2565-2574
  • 23 Ng PC, Henikoff S. SIFT: predicting amino acid changes that affect protein function. Nucleic Acids Res 2003; 31 (13) 3812-3814
  • 24 Weisschuh N, Wolf C, Wissinger B, Gramer E. A clinical and molecular genetic study of German patients with primary congenital glaucoma. Am J Ophthalmol 2009; 147 (04) 744-753
  • 25 Chavarria-Soley G, Michels-Rautenstrauss K, Caliebe A, Kautza M, Mardin C, Rautenstrauss B. Novel CYP1B1 and known PAX6 mutations in anterior segment dysgenesis (ASD). J Glaucoma 2006; 15 (06) 499-504
  • 26 Kelberman D, Islam L, Jacques TS. et al. CYP1B1-related anterior segment developmental anomalies novel mutations for infantile glaucoma and von Hippel's ulcer revisited. Ophthalmology 2011; 118 (09) 1865-1873