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M. Ali, A. Booth, A.-L. Murphy, G. Williams, H. Jafri, Y. Rashid, C. F. Inglehearn, M. McKibbin; Primary Congenital Glaucoma (PCG) in Pakistan. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5122.
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PCG usually manifests within the first three years of life and is characterised by high intra-ocular pressure (IOP) which, if uncontrolled, rapidly leads to optic nerve damage and permanent loss of vision. Affected children typically present with tearing, photophobia, corneal clouding and enlargement of the globe or cornea. It is inherited as a recessive condition and has been linked to three loci, GLC3A on 2p21 where the responsible gene is CYP1B1, and GLC3B and 3C on chromosomes 1p36 and 14q24 respectively, for which the genes involved remain to be identified. This study investigated the genetic basis and phenotype of PCG in consanguineous Pakistani pedigrees.
Three consanguineous PCG families from Northern Pakistan were investigated. Affected individuals underwent ophthalmic examination. DNA was extracted from venous blood samples. Linkage to known PCG loci was screened for using highly informative microsatellite markers genotyped on an ABI3130 DNA Analyser. Exons of CYP1B1 were then PCR amplified and sequenced.
Affected family members exhibited photophobia and nystagmus from birth. Those who had undergone drainage surgery had small, phthisical eyes, while untreated individuals had corneal clouding, raised IOP and buphthalmos (corneal diameters up to 15mm). No obvious difference was observed between families. Microsatellite genotyping revealed linkage to GLC3A (CYP1B1) in two families, while a third was linked to GLC3C. Mutation screening in the CYP1B1 linked families showed that one was homozygous for the previously reported missense mutation R390H while the second was a compound heterozygote for R390H and a novel mutation, S464T.
We report a new PCG mutation in CYP1B1 and show that the R390H mutation, previously reported in US patients of Asian origin and in an Iranian patient series, is also present in multiple Pakistani PCG cases, suggesting that this may be a common cause of PCG in Asian cases. These findings give a preliminary view of the relative frequencies of the different forms of PCG in Pakistan.
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