Abstract
Epidemiologic and genetic/molecular research on glaucoma in Iran started within the past decade. A population-based study on the epidemiology of glaucoma in Yazd, a city in central Iran, revealed that 4.4% of studied individuals were affected with glaucoma: 1.6% with high tension primary open angle glaucoma (POAG), 1.6% with normal tension POAG, and 0.4% each with primary angle closure glaucoma (PACG) and pseudoexfoliation glaucoma (PEXG), and other types of secondary glaucoma. Two notable observations were the relatively high frequency of normal tension glaucoma cases (1.6%) and the large fraction of glaucoma affected individuals (nearly 90%) who were unaware of their condition. The first and most subsequent genetic studies on glaucoma in Iran were focused on primary congenital glaucoma (PCG) showing that cytochrome P450 1B1 (CYP1B1) is the cause of PCG in the majority of Iranian patients, many different CYP1B1 mutations are present among Iranian patients but only four mutations constitute the vast majority, and the origins of most mutations in the Iranians are identical by descent (IBD) with the same mutations in other populations. Furthermore, most of the PCG patients are from the northern and northwestern provinces of Iran. A statistically significant male predominance of PCG was observed only among patients without CYP1B1 mutations. Clinical investigations on family members of PCG patients revealed that CYP1B1 mutations exhibit variable expressivity, but almost complete penetrance. A great number of individuals harboring CYP1B1 mutations become affected with juvenile onset POAG. Screening of JOAG patients showed that an approximately equal fraction of the patients harbor CYP1B1 and (myocilin) MYOC mutations; MYOC is a well-known adult onset glaucoma causing gene. Presence of CYP1B1 mutations in JOAG patients suggests that in some cases, the two conditions may share a common etiology. Further genetic analysis of Iranian PCG patients led to identification of Latent-transforming growth factor beta-binding protein 2 (LTBP2) as a causative gene for both PCG and several diseases which are often accompanied by glaucomatous presentations, such as Weill-Marchesani syndrome 3 (WMS3). The findings on LTBP2 have contributed to recognize the importance of the extracellular matrix in pathways leading to glaucoma.
Highlights
Glaucoma is a heterogeneous group of optic neuropathies with common structural and functional manifestations
Screening for cytochrome P450 1B1 (CYP1B1) mutations in 104 Iranian primary congenital glaucoma (PCG) patients was performed in 2005‐2006.[40]. The four major outcomes of the study included, 1) CYP1B1 is the cause of PCG in the majority of Iranian patients, 2) many different CYP1B1 mutations are present among Iranian patients, 3) only four mutations constitute the vast majority of disease causing mutations in these patients, and 4) the origins of most mutations in the Iranians are identical by descent (IBD) with the same mutations in other populations, in countries neighboring Iran.[40]
Genetic studies are facilitated by the fact that a few mutations in CYP1B1 constitute the majority of CYP1B1 mutations which can be screened
Summary
Glaucoma is a heterogeneous group of optic neuropathies with common structural and functional manifestations. At the beginning of genetic studies on glaucoma in Iran in 2005, three PCG loci had been identified by linkage analysis of affected pedigrees including GLC3A (OMIM 231300),[33] GLC3B (OMIM 600975),[34] and GLC3C (OMIM 613085).[35] The only gene associated with GLC3A is CYP1B1 (OMIM 601771), identified through studying families of Turkish origin.[36] Disease‐causing mutations were recessive.
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