Carrier Status for p.Gly61Glu and p.Arg368His CYP1B1 Mutations Causing Primary Congenital Glaucoma in Iran
Purpose: To estimate carrier frequencies of CYP1B1 mutations p.Gly61Glu and p.Arg368His, respectively, in Talesh and the east of Guilan province in Iran with a maximum error of 2%. Previously, it was shown that these CYP1B1 mutations may be relatively prevalent in these regions.
Methods: Population-based screenings were performed. DNA was extracted from saliva samples of 1036 individuals from Talesh and 3029 individuals from the east of Guilan. P.Gly61Glu and p.Arg368His screenings were performed, respectively, by RFLP and ARMS-based PCR protocols. For confirmation, the DNA of individuals with mutations was sequenced using the Sanger protocol.
Results: Nine individuals from Talesh (0.86%; 95%CI: 0.45–1.64%) carried the p.Gly61Glu mutation, and 73 from the east of Guilan (2.41%; 95%CI: 1.91–3.04%) carried p.Arg368His. There was no significant difference in frequencies between urban and rural regions of the various cities, nor among four cities within the east of Guilan.
Conclusion: The frequencies of p.Gly61Glu carriers in Talesh and of p.Arg368His carriers in the east of Guilan were within the 95% confidence interval of a previous study based on screenings of fewer individuals. The reliability of the recent estimates is higher, as the confidence interval for p.Gly61Glu decreased from 6.5% to 1.19% and the interval for p.Arg368His decreased from 4% to 1.13%. Based on the new findings, the maximum expected frequency of p.Gly61Glu carriers in Talesh is 1.64%, and of p.Arg368His carriers in the east of Guilan is 3%. The need for performing premarital screenings in the respective cities can be evaluated.
CYP1B1, Guilan, Iran, p.Arg368His, p.Gly61Glu, Primary Congenital Glaucoma
1. Foster PJ, Buhrmann R, Quigley HA, Johnson GJ. The definition and classification of glaucoma in prevalence surveys. Br J Ophthalmol 2002;86:238–243.
2. Lewis CJ, Hedberg-Buenz A, DeLuca AP, Stone EM, Alward WLM, Fingert JH. Primary congenital and developmental glaucomas. Hum Mol Genet 2017;26:R28–R36.
3. Sarfarazi M, Stoilov I, Schenkman JB. Genetics and biochemistry of primary congenital glaucoma. Ophthalmol Clin North Am 2003;16:543–554.
4. Souma T, Tompson SW, Thomson BR, Siggs OM, Kizhatil K, Yamaguchi S, et al. Angiopoietin receptor TEK mutations underlie primary congenital glaucoma with variable expressivity. J Clin Invest 2016;126:2575–2587.
5. Gilbert CE, Canovas R, de Canovas RK, Foster A. Causes of blindness and severe visual impairment in children in Chile. Dev Med Child Neurol 1994;36:326–333.
6. Tabbara KF, Badr IA. Changing pattern of childhood blindness in Saudi Arabia. Br J Ophthalmol 1985;69:312– 315.
7. Bejjani BA, Stockton DW, Lewis RA, Tomey KF, Dueker DK, Jabak M, 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.
8. Hewitt A, Mackinnon J, Elder J, Giubilato A, Craig J, Mackey A. Familial transmission patterns of infantile glaucoma in Australia. Invest Ophthalmol Vis Sci 2005;46:3207.
9. Narooie-Nejad M, Paylakhi SH, Shojaee S, Fazlali Z, Rezaei Kanavi M, Nilforushan N, et al. Loss of function mutations in the gene encoding latent transforming growth factor beta binding protein 2, LTBP2, cause primary congenital glaucoma. Hum Mol Genet 2009;18:3969–3977.
10. Firasat S, Riazuddin SA, Hejtmancik JF, Riazuddin S. Primary congenital glaucoma localizes to chromosome 14q24.21-24.3 in two consanguineous Pakistani families. Mol Vis 2008;14:1659–1665.
11. Young TL, Whisenhunt KN, Jin J, LaMartina SM, Martin SM, Souma T, et al. SVEP1 as a genetic modifier of TEK-related primary congenital glaucoma. Invest Ophthalmol Vis Sci 2020;61:6.
12. Zhou X, Fan N, Liu X. Advances in molecular genetics of glaucoma. Zhonghua Shiyan Yanke Zazhi/Chinese J Exp Ophthalmol 2015;33:263–269.
13. Plášilová 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;36:290–294.
14. 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;42:2211–2216.
15. Chakrabarti S, Kaur K, Kaur I, Mandal AK, Parikh RS, Thomas R, et al. Globally, CYP1B1 mutations in primary congenital glaucoma are strongly structured by geographic and haplotype backgrounds. Invest Ophthalmol Vis Sci 2006;47:43–47.
16. Chitsazian F, Tusi BK, Elahi E, Saroei HA, Sanati MH, Yazdani S, et al. CYP1B1 mutation profile of Iranian primary congenital glaucoma patients and associated haplotypes. J Mol Diagnostics 2007;9:382–393.
17. Qashqai M, Suri F, Yaseri M, Elahi E. P.Gly61Glu and P.Arg368His mutations in CYP1B1 that cause congenital glaucoma may be relatively frequent in certain regions of Gilan province, Iran. J Ophthalmic Vis Res 2018;13:403–410.
18. Katibeh M, Behboudi H, Moradian S, Alizadeh Y, Beiranvand R, Sabbaghi H, et al. Rapid assessment of avoidable blindness and diabetic retinopathy in Gilan province, Iran. Ophthalmic Epidemiol 2017;24:381–387.
19. Armitage P, Beery. G. Statistical methods medical scientific. Wiley; 1987.
20. Ahmed S. Methods in survey sampling survey errors [dissertation on the internet]. The Johns Hopkins University; 2009. Available from: http://ocw.jhsph.edu/ courses/statmethodsforsamplesurveys/pdfs/lecture4.pdf
21. Hadipour Dehshal M, Ahmadvand A, Yousefi Darestani S, Manshadi M, Abolghasemi H. Secular trends in the national and provincial births of new thalassemia cases in Iran from 2001 to 2006. Hemoglobin 2013;37:124–137.
22. Madan N, Sharma S, Sood S, Colah R, Bhatia H. Frequency of β-thalassemia trait and other hemoglobinopathies in northern and western India. Indian J Hum Genet 2010;16:16–25.
23. Ratbi I, Génin E, Legendre M, Le Floch A, Costa C, Cherkaoui-Deqqaqi S, et al. Cystic fibrosis carrier frequency and estimated prevalence of the disease in Morocco. J Cyst Fibros 2008;7:440–443.
24. Chitsazian F. Assessment of frequency of mutation in exon 3 of CYP1B1 in 60 Iranian PCG patients. Master’s Degree thesis, University of Tehran, 2007.