Carrier Status for p.Gly61Glu and p.Arg368His CYP1B1 Mutations Causing Primary Congenital Glaucoma in Iran.

Ali Heshmati,Marjan Dadashzadeh,Parisa Zamanparvar,Elahe Elahi,Peyman Taghizadeh,Mahsa Alizadeh,Mehdi Yaseri,Hamid Ahmadieh,Fatemeh Suri,Hajar Khatami,Hassan Behboudi,Monireh Moradkhah Navi

doi:10.18502/jovr.v16i4.9747

Abstract

PurposeTo 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.MethodsPopulation-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.ResultsNine 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.ConclusionThe 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.

Highlights

Carrier Status of CYP1B1 Mutations; Heshmati et al Glaucoma is a major cause of irreversible blindness worldwide.[1]
On the basis of the anatomy of the anterior chamber drainage angle and age of onset, primary glaucoma is classified as primary congenital glaucoma (PCG; OMIM 231300), primary open angle glaucoma (POAG), and primary angle closure glaucoma (PACG)
Whereas earlier genetic screenings pertaining to glaucoma were performed using DNA extracted from the peripheral blood, DNA extracted from cells in the saliva was used in the present study.[15, 17]

Summary

Introduction

Glaucoma is a major cause of irreversible blindness worldwide.[1]. On the basis of the anatomy of the anterior chamber drainage angle and age of onset, primary glaucoma is classified as primary congenital glaucoma (PCG; OMIM 231300), primary open angle glaucoma (POAG), and primary angle closure glaucoma (PACG). PCG which is the subject of this report is the most severe form of glaucoma.[2] It is characterized by an anatomical defect (trabeculodysgenesis) in the trabecular meshwork and the age of onset in the neonatal period or before the age of three years.[3] PCG occurs in both sporadic and familial patterns. Inheritance is usually autosomal recessive.[3, 4] While less common than the adult onset forms, PCG is an important cause of childhood blindness.[5, 6] The incidence of PCG is geographically and ethnically variable, and highest in populations with high rates of consanguineous marriages such as Saudi Arabia (1:2500).[7, 8]

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