About MEAJO | Editorial board | Search | Ahead of print | Current Issue | Archives | Instructions to authors | Online submission | Subscribe | Advertise | Contact | Login 
Middle East African Journal of Ophthalmology Middle East African Journal of Ophthalmology
Users Online: 915   Home Print this page Email this page Small font sizeDefault font sizeIncrease font size

  Table of Contents 
Year : 2011  |  Volume : 18  |  Issue : 1  |  Page : 7-16  

Primary congenital glaucoma and the involvement of CYP1B1

1 Kallam Anji Reddy Molecular Genetics Laboratory, Prof. Brien Holden Eye Research Centre, L.V. Prasad Eye Institute, Hyderabad, India
2 Jasti V Ramanamma Childrens Eye Care Center, Prof. Brien Holden Eye Research Centre, L.V. Prasad Eye Institute, Hyderabad, India

Date of Web Publication19-Jan-2011

Correspondence Address:
Subhabrata Chakrabarti
Champalimaud Translational Centre, Prof. Brien Holden Eye Research Centre, L.V. Prasad Eye Institute, Banjara Hills, Hyderabad - 500 034
Login to access the Email id

Source of Support: Study was partially supported by a grant from the Champalimaud Foundation, Portugal and the Department of Biotechnology, Government of India, through a Program Support Grant (BT/01/ COE/06/02/10) to Dr. Subhabrata Chakrabarti,, Conflict of Interest: None

DOI: 10.4103/0974-9233.75878

Rights and Permissions

Primary congenital glaucoma (PCG) is an autosomal recessive disorder in children due to the abnormal development of the trabecular meshwork and the anterior chamber angle. With an onset at birth to early infancy, PCG is highly prevalent in inbred populations and consanguinity is strongly associated with the disease. Gene mapping of PCG-affected families has identified three chromosomal loci, GLC3A, GLC3B and GLC3C, of which, the CYP1B1 gene on GLC3A harbors mutations in PCG. The mutation spectra of CYP1B1 vary widely across different populations but are well structured based on geographic and haplotype backgrounds. Structural and functional studies on CYP1B1 have suggested its potential role in the development and onset of glaucomatous symptoms. A new locus (GLC3D) harboring the LTBP2 gene has been characterized in developmental glaucoma but its role in classical cases of PCG is yet to be understood. In this review, we provide insight into PCG pathogenesis and the potential role of CYP1B1 in the disease phenotype.

Keywords: CYP1B1, Gene, Glaucoma, Mutation

How to cite this article:
Kaur K, Mandal AK, Chakrabarti S. Primary congenital glaucoma and the involvement of CYP1B1. Middle East Afr J Ophthalmol 2011;18:7-16

How to cite this URL:
Kaur K, Mandal AK, Chakrabarti S. Primary congenital glaucoma and the involvement of CYP1B1. Middle East Afr J Ophthalmol [serial online] 2011 [cited 2021 Dec 5];18:7-16. Available from: http://www.meajo.org/text.asp?2011/18/1/7/75878

   Introduction Top

Primary congenital glaucoma (PCG) is an ocular developmental anomaly that occurs due to the obstruction in the drainage of the aqueous humor outflow caused by the abnormal development of the trabecular meshwork (TM) and the anterior chamber angle. [1] PCG manifests during neonatal or early infantile period and is characterized by elevated intraocular pressure (IOP), megalocornea, and Haab's striae. Additional clinical features include corneal edema due to the elevated IOP that results in corneal haze, photophobia, ephiphora, and blepharospasm. [1]

   Prevalence of PCG Worldwide Top

The prevalence of PCG ranges from 1 in 1250 among the Gypsy population of Slovakia, 1 in 2,500 among the Saudi Arabians to 1 in 20,000 in the Western populations. [2],[3] The high rate of consanguinity among Slovakian Gypsies accounts for the increased prevalence of PCG. In Southern India, the prevalence of PCG is estimated at 1 in 3300 live births accounting for 4.2% of overall childhood blindness. [4]

Genetics of PCG

The genetic basis of the disease was based on the segregation of PCG in families. For the first time, the endemic occurrence of PCG was observed in the Jewish population of Algiers. Later PCG was suggested to be an autosomal recessive disorder based on its inheritance pattern in a Swedish family. [5] The high rate of concordance among monozygotic and disconcordance among the dizygotic twins also provided an additional genetic basis for PCG. [2] The autosomal recessive mode of inheritance was also supported by the prevalence of consanguinity among the affected families and was the most common mode of inheritance reported in various studies. [5] However, pseudominance has been observed in some pedigrees due to high rate of consanguinity and inbreeding in certain ethnic groups. [6]

Candidate Loci in PCG

Currently, three chromosomal loci have been implicated in PCG on GLC3A at 2p21-22, [7] GLC3B at 1p36.2-36.1, [8] and GLC3C at 14q24.3. [9]

(a) GLC3A

The GLC3A locus was mapped based on a study on 17 Turkish families comprising 113 individuals. [7] These families had a diagnosis of bilateral PCG within the first 6 months of birth without any other associated abnormality. Linkage analysis and further refinement suggested that 85% of the families showed homogeneity to the linked markers indicating that this region (2p21-22) was a major locus for PCG. This region was termed as GLC3A, where "GLC" was the designated symbol for glaucoma, "3" for congenital glaucoma and "A" as the first mapped locus in PCG. [7]

A similar study on seven PCG Slovakian Rom families based on homozygosity mapping and recombination events mapped the disease locus at an interval of 8 cM between D2S1788 and D2S1356. Genetic homogeneity in all these families was attributed to endogamy and high rate of inbreeding. [10]

(b) GLC3B

The second PCG locus was mapped to 1p36.2-36.1 through a study of eight PCG families that did not reveal linkage to GLC3A. [8] A whole genome scan was conducted on these families with 126 short tandem repeat (STR) markers. The position of GLC3B was confirmed and the significant heterogeneity indicated the existence of another locus for PCG. [8]

(c) GLC3C

The third locus for PCG was mapped to 14q24.3 and was named as GLC3C. [9] This study was carried out on a five-generation consanguineous family. On exclusion of GLC3A and GLC3B in this family, a whole genome scan was done with 235 STRs that led to the identification of homozygosity with only marker (D14S53) at 14q in the all the affected members. Further refinement revealed the homozygosity of the haplotype in all the affected members. [9]

   Identification of Candidate Genes Top

In 1995, Sarfarazi and co-workers established the critical region for the identification of the candidate gene on GLC3A using Yeast artificial chromosome (YAC) screening and radiation hybrid mapping. [7] On the basis of sequence tagged sites (STS) and expressed sequence tag (EST) maps of the human genome, the position of various STR markers linked to GLC3A was refined. [11] The critical region for GLC3A harbored two genes, human cytochrome P4501B1 (CYP1B1) and protein kinase interferon-inducible double stranded RNA-activated gene (PRKR), and a guanine nucleotide exchange factor for RAS (hSOS1). The splicing factor, arginine/serine-rich, 7 (SFRS7) gene was also mapped within the critical region by a BLAST search. As the pathophysiology of PCG was unknown and there was no prior evidence of an association of these genes to the disease phenotype, all of these were considered potential candidates. The coding regions of these genes were screened by direct sequencing that excluded hSOS1 and PRKR as no variations were observed between them. However three different frameshift mutations were detected (two deletions and one insertion) in CYP1B1 in three families that segregated in the affected individuals and were absent in 470 normal chromosomes.

The GLC3B (1p36.2-1p36.1) has been reported to be a GC-rich region and harbors a number of tumor suppressor genes. [12] These genes are associated with various malignancies yet none of them have segregated with PCG. Similarly, seven genes are known to harbor the GLC3C region: Neurexin 3A, Nuclear Receptor ERRB2, KIAA0759, Glutathione Transferase Zeta 1, Maleylacetoacetate Isomerase, Serine Palmitoyl Transferase Subunit II and Alk B protein Homologue. However, none of these genes have been characterized so far in PCG.

Cytochrome P4501B1 (CYP1B1; 2p21-2p22)

The CYP1B1 gene harbors more than 70 mutations in PCG among various ethnic groups ( http://www.hgmd.cf.ac.uk/ac/index.php ). The cytochrome P450 (CYP450) is a superfamily of closely related heme proteins found throughout the phylogenetic spectrum of plants and animals. The term CYP450 arises from the presence of a heme group and their maximum absorption at 450 nm, which is unique for these proteins and serves as their signature. [13] Cytochrome P450 proteins have an average mass of approximately 50 kDa. These are mostly membrane bound, anchored to the endoplasmic reticular membrane or the inner mitochondrial membrane with few soluble forms found in bacteria. [14] Structurally they consist of a hydrophobic amino terminal region, a proline-rich region, a carboxyl terminal portion that consists of a set of conserved core structures and signature sequences and a substrate binding region, which is a less conserved region between the hinge region and the conserved core structure. [14]

The cytochrome P450 1B1 (CYP1B1) is the only member in the CYP1B subfamily and shares 40% homology with two members in the CYP1A subfamily (CYP1A1 and CYP1A2). [15] CYP1B1 has the highest catalytic activities toward several polycyclic aromatic hydrocarbons that are the most potent inducers of mammary tumors and lung cancers. [16] Apart from these exogenous compounds CYP1B1 is also involved in the metabolism of endogeneous steroids such as 17β estradiol. A significantly higher expression with elevated 4-hydroxy estradiol production has been found in various tumor tissues including breast, uterus, prostate, lungs, than in the normal tissues.

It has been demonstrated that single nucleotide polymorphisms (SNPs) in CYP1B1 (R48G, A119S, and V432L) exhibit altered kinetics for hydroxylation of estradiol. [17],[18] These SNPs show significant associations with various cancers with respect to the genotypic and allelic frequencies in patients than controls. [19],[20],[21] Thus alterations in these residues are likely to affect the activity of the enzyme and may influence the susceptibility of individuals toward endogenous and exogenous carcinogens. [22]

CYP1B1 expression in Ocular Tissues

CYP1B1 protein expresses in various human ocular tissues including cornea, ciliary body, iris, and retina. However, no expression has been identified in TM. Interestingly, an increased CYP1B1 expression has been identified in fetal eyes compared to the adult eyes. This observation makes it tempting to speculate that CYP1B1 in the eye metabolizes an important substrate that plays a key role in the development and maturation of ocular tissues. [23] However, an entirely opposite scenario has been observed in the mouse ocular tissues. For example, a study that evaluated the spatio-temporal expression of CYP1B1 in mouse eye ontogeny revealed that the expression increases with age. [24] Based on the observations of these two studies, it can be suggested that CYP1B1 expression pattern is different in these two species.

Use of CYP1B1 Knockout Mice to Determine Its role in PCG pathogenesis

To investigate the role of CYP1B1 in PCG, Cyp1b1 knockout ( Cyp1b1 -/- ) mice were generated by targeted gene disruption in embryonic stem cells. However, gross examination of the eyes of these Cyp1b1 -/- mice neither showed any evidence of glaucoma nor any systemic abnormalities suggesting that CYP1B1 is not required for mammalian development. [25]

Similarly, the Cyp1b1 -/- mice created by Libby and co-workers (2003) showed no gross abnormalities with their IOP being indistinguishable from the wild mice. [26] However, histological and electron microscopic analysis revealed abnormalities in the eyes of Cyp1b1 -/- mice such as small or no Schlemm's canal, basal lamina extending from the cornea over the TM and attachments of iris to TM and peripheral cornea. These observations indicate that even though the Cyp1b1 -/- mice did not exhibit features of classical PCG, the anterior chamber angle abnormalities indicated the potential role of CYP1B1 in the development of these ocular structures. [26]

Potential Role of CYP1B1 in development through retinoic acid-mediated signaling

CYP1B1 has been shown to metabolize the two step oxidative synthesis of retinoic acid (RA) from retinol. RA is a ligand for various nuclear receptor proteins and is known to regulate morphogenesis. The two step oxidative synthesis of RA can be metabolized by various retinaldehyde dehydrogenases (RALDH) such as RALDH-1, RALDH-2, and RALDH-3. In order to correlate the RA synthesis by CYP1B1, Chambers and co-workers (2007) studied regions in chicks, which are rich in RA production and CYP1B1 synthesis but are deficient in RALDH expression. [27] These authors studied the ectopic expression of CYP1B1 and in turn its effect on the transcription of developmental genes, which are known to be regulated by RA. Furthermore, they found that ectopic expression of CYP1B1 resulted in the downregulation of two such developmental genes, i.e. Shh (sonic hedgehog homolog of drosophila) that regulates the vertebrate organogenesis and Nkx6.1 (NK homeobox family 6), involved in the development of beta cells in endocrine pancreas. [27] Based on these findings, it was suggested that CYP1B1 might play an important role in the development via RA-mediated signaling pathways.

Mutation spectrum of CYP1B1 worldwide

More than 70 distinct mutations ( http://www.hgmd.cf.ac.uk/ac/index.php ) in CYP1B1 have been described in PCG indicating the genetic heterogeneity of the condition [Table 1]. The prevalence of CYP1B1 mutations ranges from 20% in Japanese, [28] 33.3% in Indonesians, [29] 44% among Indians, [30] 50% among the Brazilians [6] to almost 100% among the Saudi Arabians [31] and Slovakian Gypsies. [32] The relatively higher prevalence of these mutations in the latter two populations could be attributed to consanguinity and inbreeding.
Table 1 :Worldwide distribution of CYP1B1 mutations

Click here to view

The majority of these mutations are missense mutations affecting the amino acid residues located either in the hinge region or the conserved core structures in the cytosolic region [Table 2]. These mutations, therefore, are expected to interfere with fundamental properties of the protein such as folding, heme binding, substrate accommodation, and interaction with the redox partner. [14] As these mutations have been identified throughout the gene, there are no major hot spot regions in the CYP1B1.
Table 2 :Distribution of different types of CYP1B1 mutations worldwide

Click here to view

Prevalent Mutations in CYP1B1

Among the various CYP1B1 mutations, the G61E was the most prevalent mutation in 69.3% (43/62) of Saudi Arabians and 29% (30/104) of Iranian patients [Table 3]. Apart from G61E, the R390H and R368H mutations were also identified with a higher frequency (20.1% and 10.6%, respectively) in Iranian patients. In the Saudi Arabian population, 44.2% (19/43) of the patients with G61E did not manifest the disease at presentation, indicating the incomplete penetrance of this mutation. [31] In the Iranian population, 26/29 cases with G61E were bilateral with an age of onset within 3 months of life and raised IOP. [36]
Table 3 :Prevalent CYP1B1 mutations in different PCG populations

Click here to view

E387K was the only mutation identified in all the 20 PCG cases among the Slovakian gypsies suggesting a single ancestral mutational event [Table 3]. The common haplotype background of the patients harboring this mutation further confirmed the founder effect of E387K mutation in this population. [32]

In the Brazilian population, 4340delG was the most predominant mutation identified in 23% (12/52) of cases [Table 3]. All patients with 4340delG had bilateral disease with an age at onset within the first month of life and IOP ranging from 25 to 55 mmHg. [6]

The R368H mutation was the most predominant CYP1B1 mutant allele identified in PCG among Indian cases [Table 3]. However, clinically there was no association of severity of the disease phenotype with this mutation. [37],[42]

Clustering of prevalent CYP1B1 mutations on Common Haplotype Backgrounds

Haplotypes generated with five intagenic SNPs (R48G, A119S, V432L, D449D and N453S) in CYP1B1 in different populations indicated that the "C-G-G-T-A" was the most prevalent haplotype amongst PCG cases harboring CYP1B1 mutations, while the "G-T-C-C-A" was the most common haplotype among the controls. [39] Most of the common mutations in different populations were found to cluster on the "C-G-G-T-A" haplotype and thus this must have been an ancient haplotype. An extensive haplotype analysis supplemented by evolutionary insights suggested that the clustering of mutations from different geographical regions on the same haplotype background is suggestive of their common founder effects. Also, the occurrence of the same mutation on similar haplotype backgrounds in different geographical regions is probably due to human migration. [39] This phenomenon has also been observed in cases with CYP1B1 mutations in primary open angle and primary angle closure glaucomas. [57]

Interaction of CYP1B1 with Other Genes

Myocilin (MYOC), a candidate gene for juvenile and adult onset forms of primary open angle glaucoma, may have been involved with CYP1B1 through a digenic mechanism in a glaucoma family of East Indian (Guyanese) origin. It has been suggested that congenital glaucoma and juvenile glaucoma are allelic variants of CYP1B1 and that CYP1B1 and MYOC might act through common biochemical pathways with CYP1B1 acting as a modifier for MYOC. [58] Digenic interactions of MYOC and CYP1B1 alleles have also been reported in cases of PCG. [59]

CYP1B1 has also been reported to interact with tyrosinase (Tyr), a candidate gene for ocular albinism that codes for a protein which converts tyrosine to L-dopa, a precursor of catecholamines and an important regulator in development. Tyr has been identified as a modifier in iridocorneal angle defects present in CYP1B1 knockout mice. It has been observed that mice lacking both CYP1B1 and Tyr had severe iridocorneal angle malformations than those lacking only CYP1B1. [26] Also some albinos are reported to have anterior segment dysgenesis and congenital glaucoma suggesting the possible role of Tyr in congenital glaucoma. It has been hypothesized that Tyr may affect the angle development through modulation of L-dopa as treatment of L-dopa was found to prevent the severe angle dysgenesis present in mice lacking both CYP1B1 and Tyr.

However, TYR did not show any association with human PCG patients. Bidinost and co-workers (2006) conducted a genome wide scan on 97 individuals from 17 Saudi Arabian families of whom, 58 had homozygous or compound heterozygous mutations in CYP1B1.[60] The genome wide scan did not show any significant evidence for a co-segregating locus and resequencing of TYR did not reveal any mutations in PCG. Thus, it was suggested that TYR was not a modifier for CYP1B1 mutations in humans and the possible role of TYR in normal human eye development may be different from that in the mouse. [60]

CYP1B1 mutations with PCG pathogenesis

The exact role of CYP1B1 in the development of eye and its association with PCG is not known. Various in silico and in vitro studies have been carried out to determine the impact of the mutations in CYP1B1 on the structure and function of the protein. The findings of these studies can help in a better understanding of the association of CYP1B1 with the disease pathogenesis.

Recently, Hollander and co-workers tried to correlate CYP1B1 mutations with the degree of angle dysgenesis observed histologically and disease severity in terms of age at diagnosis and difficulty in controlling IOP in six congenital glaucoma patients. [61] Their findings suggested that CYP1B1 mutations could be classified based on histological findings, which may be used to correlate these mutations with disease severity.

Certain CYP1B1 mutations have been analyzed in-silico for their possible impact on the protein structure and function. Comparative modeling of the human CYP1b1 using the X-ray structure of CYP2c9 as a template along with molecular dynamics simulations revealed several structural differences that would potentially impact the functional domains. [62]

In vitro studiesto determine the effect of CYP1B1 mutations on the stability and function of the protein was carried out by Jansson and co-workers. [63] These authors studied the effect of two missense mutations (G61E and R469W) on the stability and enzymatic activity of CYP1B1. It was observed that G61E mutant had lost 60% of its stability, while R469W retained about 80% of the stability compared to the wild type. The effects of the mutants on the function of protein were further determined by an enzymatic assay that further confirmed their decreased metabolic activity (50-70%) for all the substrates when compared to the wild protein. [63]

Similarly, Bagiyeva and co-workers compared the enzymatic activity of the two other mutant (R117W and G329V) proteins with the wild type. While there was no apparent difference in the expression levels of wild type and mutant proteins, there was a decreased enzymatic activity of mutant proteins compared to the wild type. This was attributed to the slow CYP1B1 traffic through ER in cases of mutant CYP1B1 that further contributed to the lower enzyme activity and that could lead to PCG pathogenesis. [38]

Hypothesis for the Possible Role of CYP1B1 in PCG Pathogenesis

Although the exact function of CYP1B1 protein in the eye is still unclear but as it is a mono-oxygenase, the following scenarios may be expected for its role in the development of the eye.

CYP1B1 is involved in the generation of some morphogen that plays an important role in the development of the TM and other components in the outflow system by regulating the spatial and temporal expression of genes controlling anterior chamber angle development. Hence mutations in CYP1B1 might result in the absence of the morphogen, which in turn alters the expression of genes. [14]

Alternatively, CYP1B1 eliminates some active morphogen and prevents its signal capacity from dispersing beyond the specific cells upon which it must act. Hence the mutations in CYP1B1 might result in the accumulation of this metabolite producing toxic effects, which in turn may lead to developmental arrest. [14]

Although the absence of the orthologous enzyme in mouse (knockout mouse) did not show any evidence of glaucoma, this might be due to the less sensitive methods having been used to evaluate glaucomatous changes in the mouse. In addition, the mouse phenotype may differ from humans, since the anterior chamber angle has undergone evolutionary changes as evident from the differences in the TM in humans and higher apes as opposed to a reticular type meshwork in lower organisms. [14],[64]

A recent study carried by Rojas and coworkers [65] attempted to determine the pathogenic mechanisms of the disease by comparing trabeculectomy specimens of congenital glaucoma patients with normal human eyes, both at the histological and ultrastructural levels. They found accumulation of amorphous material in the TM, insertion of iris in TM, bulky endothelial cells in Schlemms canal, and increase in the size of trabeculae. Based on these findings, it was concluded that abnormalities in the TM structure could result in the disease phenotype. [65]

Genotype Phenotype Correlation with Respect to CYP1B1 Mutations

Despite a number of PCG-associated mutations in CYP1B1, little evidence exists of direct correlation of the mutant genotype with the disease phenotype. Such an association has been demonstrated in a Brazilian population where the most prevalent mutation (4340delG), identified in 21 out of 52 (20.2%) of the PCG cases, exhibited a very severe phenotype. [6] The clinical evaluation of 12 individuals with this mutation revealed that all were bilateral cases, with an early onset of the disease (≤1 month of life) and with a maximum IOP ranging between 25 and 55 mmHg. These patients had a poor response to surgery when compared to those who did not have this mutation. [6]

On the other hand there are some reports about the variable expression of the disease phenotype. Four affected individuals in an American PCG family were found to be compound heterozygotes for the E387K and 268del SNF. But only two of them manifested a severe form of the disease with IOP of 25 and 28 mmHg in the right and left eyes, respectively, and corneal edema, whereas, the other two did not show any symptoms until their mid-teens. [52]

Two PCG patients along with a JOAG case from Costa Rica were reported to harbor the same homozygous (g.8037-8046dup) mutation. [53] These patients had a maximum IOP of 22 and 24 mmHg, respectively. The former patient underwent two surgeries in the right eye and six surgeries in the left eye, whereas the latter patient underwent two surgeries in both eyes. All the three cases did not harbor any MYOC mutation. The presence of the same mutated allele resulting in manifestation of the disease symptoms at different age indicates the possible relationship between the genotype and the environmental factors.

A study from India on 146 Indian PCG patients tried to correlate the genotype of patients screened for six different mutations (Ins376 A, P193L, E229K, R390C, G61E and R368H) to disease severity. Accordingly, a severity index was prepared that included corneal diameter, IOP, cup to disk ratio, corneal clarity, and last recorded visual acuity. [42] Cases with frameshift mutation (ins376A) had the worst phenotype followed by those with homozygous R390C mutation. In addition 80% of the cases with E229K, 72% with R368H, 66.7% with G61E and 62.5% with P193L exhibited a severe phenotype in at least one eye. [42]

A study on the Arab-Bedouin PCG cases determined the prognostic factors for surgical outcomes in cases that underwent intervention within the first 3 months of birth. [66] The initial measure of outcome was based on surgical intervention, which was considered successful when normal IOP (<21 mmHg) was attained without antiglaucoma medication. The final outcome was considered a success when IOP was between 5 and 21 mmHg at the end of 2 year follow-up without anti-glaucoma medication irrespective of the number of surgical interventions. It was observed that among the patients with a failure in the first outcome, the initial IOP was higher (40.47 ± 11.06) compared to the group with lower IOP (34.14 ± 4.95) where it was a success. [68] However, there was no association with the mean age at intervention, corneal diameter, and cup to disk ratio with the final outcome. [66]

   Conclusions Top

PCG is a clinical and genetically heterogeneous condition with CYP1B1 as the major candidate gene. PCG-associated CYP1B1 mutations have been reported worldwide in different populations with varying prevalence. However, CYP1B1 alone cannot explain the overall genetic contributions in PCG. The exact role of this gene in the pathophysiology of the disease remains unknown. However, various in vitro and in-silico studies have demonstrated the pathogenic nature of the identified mutations. While several studies have been undertaken on PCG and CYP1B1 but there is a dearth of studies in understanding the genetic basis of cases without CYP1B1 mutations. Some attempts in understanding the molecular involvement of candidate genes such as MYOC and FOXC1 have not indicated any major involvements. [59],[67] The mapping of a new locus (GLC3D) on 14q24, which is distal to GLC3C has been characterized to harbor mutations in the LTBP2 gene in developmental glaucomas. [68] While this is a promising development but its role in classic cases of PCG and those devoid of mutations in CYP1B1 would be interesting.

Since PCG is a congenital disorder, an early and reliable diagnosis is vital, so that appropriate and prompt medical and/or surgical intervention can be initiated. This could prevent unwanted vision loss and also reduce the burden of childhood blindness. Some attempts in understanding the molecular basis through genome wide association studies and whole genome resequencing approaches are underway and may provide valuable insight regarding the underlying mechanisms. A comprehensive understanding of PCG-associated mutations in candidate genes would be helpful in developing a reliable diagnostic method for screening in the predisposed families that would eventually aid in predictive testing and better prognosis.

   Acknowledgements Top

The study was partially supported by a grant from the Champalimaud Foundation, Portugal and the Department of Biotechnology, Government of India, through a Program Support Grant (BT/01/COE/06/02/10) to Dr. Subhabrata Chakrabarti.

   References Top

1.Mandal AK, Netland PA. The pediatric glaucomas. Elsevier's Butterworth Heinemann; 2006.  Back to cited text no. 1
2.Gencik A. Epidemiology and genetics of primary congenital glaucoma in Slovakia: Description of a form of primary congenital glaucoma in gypsies with autosomal recessive inheritance and complete penetrance. Dev Ophthalmol 1989;16:76-115.  Back to cited text no. 2
3.Gencik A, Gencikova A, Ferák V. Population genetical aspects of primary congenital glaucoma: I, Incidence, prevalence, gene frequency, and age of onset. Hum Genet 1982;61:193-7.  Back to cited text no. 3
4.Dandona L, Williams JD, Williams BC, Rao GN. Population - based assessment of childhood blindness in Southern India. Arch Ophthalmol 1998;116:545-46.  Back to cited text no. 4
5.Sarfarazi M, Stoilov I. Molecular genetics of primary congenital glaucoma. Eye 2000;14:422-8.  Back to cited text no. 5
6.Stoilov IR, Costa VP, Vasconcellos JP, Melo MB, Betinjane AJ, Carani JC, et al. Molecular genetics of primary congenital glaucoma in Brazil. Invest Ophthalmol Vis Sci 2002;43:1820-7.  Back to cited text no. 6
7.Sarfarazi M, Akarsu AN, Hossain A, Turacli ME, Aktan SG, Barsoum-Homsy M, et al. Assignment of a locus (GLC3A) for primary congenital glaucoma (Buphthalmos) to 2p21 and evidence for genetic heterogeneity. Genomics 1995;30:171-7.  Back to cited text no. 7
8.Akarsu AN, Turacli ME, Aktan SG, Barsoum-Homsy M, Chevrette L, Sayli BS, et al. A second locus (GLC3B) for primary congenital glaucoma (Buphthalmos) maps to the 1p36 region. Hum Mol Genet 1996;5:1199-203.  Back to cited text no. 8
9.Stoilov IR, Sarfarazi M. Third genetic locus (GLC3C) for primary congenital glaucoma (PCG) maps to chromosome 14q24.3. Invest Ophthalmol Vis Sci 2002;43E3015.  Back to cited text no. 9
10.Plásilová M, Feráková E, Kádasi L, Poláková H, Gerinec A, Ott J, et al. Linkage of autosomal recessive primary congenital glaucoma to the GLC3A locus in Roms (Gypsies) from Slovakia. Hum Hered 1998;48:30-3.  Back to cited text no. 10
11.Stoilov I, Akarsu AN, Sarfarazi M. Identification of three different truncating mutations in cytochrome P450 1B1 (CYP1B1) as the principal cause of primary congenital glaucoma (buphthalmos) in families linked to the GLC3A locus on chromosome 2p21. Hum Mol Genet 1997;6:641-7.  Back to cited text no. 11
12.Saccone S, De Sario A, Della Valle G, Bernardi G. The highest gene concentrations in the human genome are in telomeric bands of metaphase chromosomes. Proc Natl Acad Sci USA 1992;89:4913-7.  Back to cited text no. 12
13.Hasler JA, Estabrook R, Murray M, Pikuleva I. Pharmacogenetics of cytochromes P450. Mole Aspects Med 1999;20:25-137.   Back to cited text no. 13
14.Stoilov I, Jansson I, Sarfarazi M, Schenkman JB. Role of cytochrome P-450 in development. Drug Metabol Drug Interact 2001;18:33-55.  Back to cited text no. 14
15.Murray GI, Melvin WT, Greenlee WF, Burke MD. Regulation, function, and tissue-specific expression of cytochrome P450 CYP1B1. Annu Rev Pharmacol Toxicol 2001;41:297-316.  Back to cited text no. 15
16.Shimada T, Hayes CL, Yamazaki H, Amin S, Hecht SS, Guengerich FP, et al. Activation of chemically diverse procarcinogens by human cytochrome P-4501B1. Cancer Res 1996;56:2979-84.  Back to cited text no. 16
17.Shimada T, Watanabe J, Inoue K, Guengerich FP, Gillam EM. Specificity of 17β-oestradiol and benzo (a) pyrene oxidation by polymorphic human cytochrome P4501B1 variants substituted at residues 48,119 and 432. Xenobiotica 2001;31:163-76.  Back to cited text no. 17
18.Akillu E, Oscarson M, Hidestrand M, Leidvik B, Otter C, Ingelman-Sundberg M. Functional analysis of six different polymorphic CYP1B1 enzyme variants found in an Ethopian population. Mol Paharmacol 2002;61:586-94.  Back to cited text no. 18
19.Tanaka Y, Sasaki M, Kaneuchi M, Shiina H, Igawa M, Dahiya R. Polymorphisms of the CYP1B1 gene have higher risk for prostate cancer. Biochem Biophys Res Commun 2002;296:820-6.  Back to cited text no. 19
20.Watanabe J, Shimada T, Gillam EM, Ikuta T, Suemasu K, Higashi Y, et al. Association of CYP1B1 genetic polymorphism with incidence to breast and lung cancer. Pharmacogenetics 2000;10:25-33.  Back to cited text no. 20
21.Zheng W, Xie DW, Jin F, Cheng JR, Dai Q, Wen WQ, et al. Genetic polymorphism of cytochrome P450-1B1 and risk of breast cancer. Cancer Epidemiol Biomarkers Prev 2000;9:147-50.  Back to cited text no. 21
22.Lewis DF, Gillam EM, Everett SA, Shimada T. Molecular modelling of human CYP1B1 substrate interactions and investigation of allelic variant effects on metabolism. Chem Biol Interactions 2003;145:281-95.  Back to cited text no. 22
23.Doshi M, Marcus C, Bejjani BA, Edward DP. Immunolocalization of CYP1B1 in normal, human, fetal and adult eyes. Exp Eye Res 2006;82:24-32.  Back to cited text no. 23
24.Choudhary D, Jansson I, Rezaul K, Han DK, Sarfarazi M, Schenkman JB. Cyp1b1 protein in the mouse eye during development: An immunohistochemical study. Drug Metab Dispos 2007;35:987-94.  Back to cited text no. 24
25.Buters JT, Sakai S, Richter T, Pineau T, Alexander DL, Savas U, et al. Cytochrome P450 CYP1B1 determines susceptibility to 7, 12-dimethylbenz[a]anthracene-induced lymphomas. Proc Natl Acad Sci U S A 1999;96:1977-82.  Back to cited text no. 25
26.Libby RT, Smith RS, Savinova OV, Zabaleta A, Martin JE, Gonzalez FJ, et al. Modification of ocular defects in mouse developmental glaucoma models by tyrosinase. Science 2003;299:1578-81.  Back to cited text no. 26
27.Chambers D, Wilson L, Malcolm M, Lumsden A. RALDH-independent generation pf retinoic acid during vertebrate embryogenesis by CYP1B1. Development 2007;134:1369-83.  Back to cited text no. 27
28.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;42:2211-6.  Back to cited text no. 28
29.Sitorus R, Ardjo SM, Lorenz B, Preising M. CYP1B1 gene analysis in primary congenital glaucoma in Indonesian and European patients. J Med Genet 2003;40:e9.   Back to cited text no. 29
30.Chakrabarti S, Ghanekar Y, Kaur K, Kaur I, Mandal AK, Rao KN, et al. A polymorphism in the CYP1B1 promoter is functionally associated with primary congenital glaucoma. Hum Mol Genet 2010;19:4083-90.  Back to cited text no. 30
31.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;12:367-74.  Back to cited text no. 31
32.Plásilovs M, Stoilov I, Sarfarazi M, Kádasi L, et al. Identification of a single ancestral CYP1B1 mutation in Slovak Gypsies (Roms) affected with primary congenital glaucoma. J Med Genet 1999;36:290-4.  Back to cited text no. 32
33.Panicker SG, Reddy AB, Mandal AK, Ahmed N, Nagarajaram HA, Hasnain SE, et al. Identification of novel mutations causing familial primary congenital glaucoma in Indian pedigrees. Invest Ophthalmol Vis Sci 2002;43:1358-66.  Back to cited text no. 33
34.Reddy AB, Panicker SG, Mandal AK, Hasnain SE, Balasubramanian D. Identification of R368H as a predominant CYP1B1 allele causing primary congenital glaucoma in Indian patients. Invest Ophthalmol Vis Sci 2003;44:4200-3.  Back to cited text no. 34
35.Stoilov I, Akarsu AN, Alozie I, Child A, Barsoum-Homsy M, Turacli ME, et al. Sequence analysis and homology modeling suggest that primary congenital glaucoma on 2p21 results from mutations disrupting either the hinge region or the conserved core structures of cytochrome P4501B1. Am J Hum Genet 1998;62:573-84.  Back to cited text no. 35
36.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 Diagn 2007;9:382-93.  Back to cited text no. 36
37.Reddy AB, Kaur K, Mandal AK, Panicker SG, Thomas R, Hasnain SE, et al. Mutation spectrum of the CYP1B1 gene in Indian primary congenital glaucoma patients. Mol Vis 2004;10:696-702.  Back to cited text no. 37
38.Bagiyeva S, Marfany G, Gonzalez-Angulo O, Gonzalez-Duarte R. Mutational screening of CYP1B1 in Turkish PCG families and functional analyses of newly detected mutations. Mol Vis 2007;13:1458-68.  Back to cited text no. 38
39.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;47:43-7.  Back to cited text no. 39
40.Lσpez-Garrido MP, Sαnchez-Sαnchez F, Lσpez-Martνnez F, Aroca-Aguilar JD, Blanco-Marchite C, Coca-Prados M, et al. Heterozygous CYP1B1 gene mutations in Spanish patients with primary open-angle glaucoma. Mol Vis 2006;12:748-55.  Back to cited text no. 40
41.Belmouden A, Melki R, Hamdani M, Zaghloul K, Amraoui A, Nadifi S, et al. A novel frameshift founder mutation in the cytochrome P450 1B1 (CYP1B1) gene is associated with primary congenital glaucoma in Morocco. Clin Genet 2002;62:334-9.  Back to cited text no. 41
42.Panicker SG, Mandal AK, Reddy AB, Gothwal VK, Hasnain SE. Correlation between genotype and phenotype in Indian primary congenital glaucoma patients. Invest Ophthalmol Vis Sci 2004;45:1149-56.  Back to cited text no. 42
43.Kumar A, Basavaraj MG, Gupta SK, Qamar I, Ali AM, Bajaj V, et al. Role of CYP1B1, MYOC, OPTN, and OPTC genes in adult-onset primary open-angle glaucoma: Predominance of CYP1B1 mutations in Indian patients. Mol Vis 2007;13:667-76.  Back to cited text no. 43
44.Acharya M, Mookherjee S, Bhattacharjee A, Bandyopadhyay AK, Daulat Thakur SK, Bhaduri G, et al. Primary role of CYP1B1 in Indian juvenile-onset POAG patients. Mol Vis 2006;12:399-404.  Back to cited text no. 44
45.Colomb E, Kaplan J, Garchon HJ. Novel cytochrome P4501B1 (CYP1B1) mutations in patients with primary congenital glaucoma in France. Hum Mut 2003;22:496.  Back to cited text no. 45
46.Melki R, Colomb E, Lefort N, Brιzin AP, Garchon HJ. CYP1B1 mutations in French patients with early-onset primary open-angle glaucoma. J Med Genet 2004;41:647-51.  Back to cited text no. 46
47.Dimasi DP, Hewitt AW, Straga T, Pater J, MacKinnon JR, Elder JE, et al. Prevalence of CYP1B1 mutations in Australian patients with primary congenital glaucoma. Clin Genet 2007;72:255-60.  Back to cited text no. 47
48.Ohtake Y, Tanino T, Suzuki Y, Miyata H, Taomoto M, Azuma N, et al. Phenotype of cytochrome P4501B1 gene (CYP1B1) mutations in Japanese patients with primary congenital glaucoma. Br J Ophthalmol 2003;87:302-4.  Back to cited text no. 48
49.Michels-Rautenstrauss KG, Mardin CY, Zenker M, Jordan N, Gusek-Schneider GC, Rautenstrauss BW. Primary congenital glaucoma: Three case reports on novel mutations and combinations of mutations in the GLC3A (CYP1B1) gene. J Glaucoma 2001;10:354-7.  Back to cited text no. 49
50.Alfadhli S, Behbehani A, Elshafey A, Abdelmoaty S, Al-Awadi S. Molecular and clinical evaluation of primary congenital glaucoma in Kuwait. Am J Ophthalmol 2006;141:512-6.  Back to cited text no. 50
51.Bejjani BA, Lewis RA, Tomey KF, Anderson KL, Dueker DK, Jabak M, et al. Mutations in CYP1B1, the gene for cytochrome P4501B1, are the predominant cause of primary congenital glaucoma in Saudi Arabia. Am J Hum Genet 1998;62:325-33.  Back to cited text no. 51
52.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:e6.  Back to cited text no. 52
53.Chavarrνa-Soley G, Rautenstrauss BI, Azofeifa J. Glaucoma in Costa Rica: Initial approaches. Rev Biol Trop 2004;52:507-20.  Back to cited text no. 53
54.Curry SM, Daou AG, Hermanns P, Molinari A, Lewis RA, Bejjani BA. Cytochrome P4501B1 mutations cause only part of primary congenital glaucoma in Ecuador. Ophthal Genet 2004;25:3-9.  Back to cited text no. 54
55.Messina-Baas OM, Gonzαlez-Huerta LM, Chima-Galαn C, Kofman-Alfaro SH, Rivera-Vega MR, Babayαn-Mena I, et al. Molecular analysis of the CYP1B1 gene: Identification of novel truncating mutations in patients with primary congenital glaucoma. Ophthal Res 2007;39:17-23.  Back to cited text no. 55
56.El-Ashry MF, Abd El-Aziz MM, Bhattacharya SS. A clinical and molecular genetic study of Egyptian and Saudi Arabian patients with primary congenital glaucoma (PCG). J Glaucoma 2007;16:104-11.  Back to cited text no. 56
57.Chakrabarti S, Devi KR, Komatireddy S, Kaur K, Parikh RS, Mandal AK, et al. Glaucoma-associated CYP1B1 mutations share similar haplotype backgrounds in POAG and PACG phenotypes. Invest Ophthalmol Vis Sci 2007;48:5439-44.  Back to cited text no. 57
58.Vincent AL, Billingsley G, Buys Y, Levin AV, Priston M, Trope G, et al. Digenic inheritance of early-onset glaucoma: CYP1B1, a potential modifier gene. Am J Hum Genet 2002;70:448-60.  Back to cited text no. 58
59.Kaur K, Reddy AB, Mukhopadhyay A, Mandal AK, Hasnain SE, Ray K, et al. Myocilin gene implicated in primary congenital glaucoma. Clin Genet 2005;67:335-40.  Back to cited text no. 59
60.Bidinost C, Hernandez N, Edward DP, Al-Rajhi A, Lewis RA, Lupski JR, et al. Of mice and men: Tyrosinase modification of congenital glaucoma in mice but not in humans. Invest Ophthalmol Vis Sci 2006;47:1486-90.  Back to cited text no. 60
61.Hollander DA, Sarfarazi M, Stoilov I, Wood IS, Fredrick DR, Alvarado JA. Genotype and phenotype correlations in congenital glaucoma. Trans Am Ophthalmol Soc 2006;104:183-95.  Back to cited text no. 61
62.Achary MS, Reddy AB, Chakrabarti S, Panicker SG, Mandal AK, Ahmed N, et al. Disease-causing mutations in proteins: Structural analysis of the CYP1B1 mutations causing primary congenital glaucoma in humans. Biophys J 2006;91:4329-39.  Back to cited text no. 62
63.Jansson I, Stoilov I, Sarfarazi M, Schenkman JB. Effect of two mutations of human CYP1B1, G61E and R469W, on stability and endogenous steroid substrate metabolism. Pharmacogenetics 2001;11:793-801.  Back to cited text no. 63
64.Gonzalez FJ, Kimura S. Study of P450 function using gene knockout and transgenic mice. Arch Biochem Biophys 2003;409:153-8.  Back to cited text no. 64
65.Rojas B, Ramνrez AI, de-Hoz R, Salazar JJ, Remνrez JM, Triviρo A. Structural changes of the anterior chamber angle in primary congenital glaucoma with respect to normal development. Arch Soc Esp Oftalmol 2006;81:65-71.  Back to cited text no. 65
66.Levy J, Carmi R, Rosen S, Lifshitz T. Primary congenital glaucoma presenting within the first three months of life in a Bedouin population: Prognostic factors. J Glaucoma 2005;14:139-44.  Back to cited text no. 66
67.Chakrabarti S, Kaur K, Rao KN, Mandal AK, Kaur I, Parikh RS, et al. The transcription factor gene FOXC1 exhibits a limited role in primary congenital glaucoma. Invest Ophthalmol Vis Sci 2009;50:75-83.  Back to cited text no. 67
68.Ali M, McKibbin M, Booth A, Parry DA, Jain P, Riazuddin SA, et al. Null mutations in LTBP2 cause primary congenital glaucoma. Am J Hum Genet 2009;84:664-71.  Back to cited text no. 68


  [Table 1], [Table 2], [Table 3]

This article has been cited by
1 Risk factors of ocular morbidity among under-five years old children in Khartoum State- Sudan- 2020
Mohanad Kamaleldin Mahmoud Ibrahim, Jacqueline Elizabeth Wolvaardt, Mustafa Khidir Mustafa Elnimeiri
Health Science Reports. 2021; 4(2)
[Pubmed] | [DOI]
2 Associations of CYP2B6 genetic polymorphisms with Hirschsprung’s disease in a southern Chinese population
Yanqing Liu, Chaoting Lan, Bingxiao Li, Ning Wang, Xiaoyu Zuo, Lihua Huang, Yuxin Wu, Yun Zhu
Journal of Clinical Laboratory Analysis. 2021;
[Pubmed] | [DOI]
3 Mutational analysis of CYP1B1 gene in Iranian pedigrees with glaucoma reveals known and novel mutations
Babak Emamalizadeh, Yousef Daneshmandpour, Somayeh Kazeminasb, Ehsan Aghaei Moghadam, Zahra Bahmanpour, Elham Alehabib, Somayeh Alinaghi, Azadeh Doozandeh, Minoo Atakhorrami, Hossein Darvish
International Ophthalmology. 2021; 41(10): 3269
[Pubmed] | [DOI]
4 Risk Factors for Blindness in Children With Primary Congenital Glaucoma—Follow-up of a Registry Cohort
Rayan Alshigari, Alia Freidi, Ches Souru, Deepak P. Edward, Rizwan Malik
American Journal of Ophthalmology. 2021; 224: 238
[Pubmed] | [DOI]
5 Genetic Epidemiology of Primary Congenital Glaucoma in the 22 Arab Countries: A Systematic Review
Sara Jemmeih, Shaza Malik, Sarah Okashah, Hatem Zayed
Ophthalmic Epidemiology. 2021; : 1
[Pubmed] | [DOI]
6 Combined trabeculotomy-trabeculectomy for primary congenital glaucoma: long-term experience from a tertiary referral centre in a developing nation
Anil K. Mandal, Vijaya K. Gothwal, Rohit Khanna
Acta Ophthalmologica. 2021;
[Pubmed] | [DOI]
7 Prenatal diagnosis of primary congenital glaucoma and histopathological features in a fetal globe with cytochrome p4501B1 mutations
Mozhgan Rezaei Kanavi, Shahin Yazdani, Elahe Elahi, Mehraban Mirrahimi, Maryam Hajizadeh, Sepideh Khodaverdi, Fatemeh Suri
European Journal of Ophthalmology. 2021; : 1120672121
[Pubmed] | [DOI]
8 Absence of Cytochrome P450-1b1 Increases Susceptibility of Pressure-Induced Axonopathy in the Murine Retinal Projection
Naseem Amirmokhtari, Brian D. Foresi, Shiv S. Dewan, Rachida A. Bouhenni, Matthew A. Smith
Frontiers in Cell and Developmental Biology. 2021; 9
[Pubmed] | [DOI]
9 Novel compound heterozygous mutations in CYP1B1 identified in a Chinese family with developmental glaucoma
Suping Cai, Daren Zhang, Xiaodong Jiao, Tingting Wang, Mengjie Fan, Yun Wang, James Hejtmancik, Xuyang Liu
Molecular Medicine Reports. 2021; 24(5)
[Pubmed] | [DOI]
10 Correlation of histopathology of trabecular meshwork with clinical features in primary congenital glaucoma
Rinky Agarwal, Seema Sen, Seema Kashyap, Tanuj Dada, Tapas Chandra Nag, Viney Gupta, Ramanjit Sihota
British Journal of Ophthalmology. 2020; : bjophthalm
[Pubmed] | [DOI]
11 Screening of West Siberian patients with primary congenital glaucoma for CYP1B1 gene mutations
D. E. Ivanoshchuk, S. V. Mikhailova, O. G. Fenkova, E. V. Shakhtshneider, A. Z. Fursova, I. V. Bychkov, M. I. Voevoda
Vavilov Journal of Genetics and Breeding. 2020; 24(8): 861
[Pubmed] | [DOI]
12 Primary Congenital Glaucoma: Trends in Presentation Over 3 Decades at a Tertiary Eye Care Center in India
Anil K. Mandal, Shaik S. Sulthana, Vijaya K. Gothwal
Journal of Glaucoma. 2020; 29(11): 1095
[Pubmed] | [DOI]
13 Girl Power in Glaucoma: The Role of Estrogen in Primary Open Angle Glaucoma
Kyrylo Fotesko, Bo Schneider Vohra Thomsen, Miriam Kolko, Rupali Vohra
Cellular and Molecular Neurobiology. 2020;
[Pubmed] | [DOI]
14 Bioinformatics analysis of CYP1B1 mutation hotspots in Chinese primary congenital glaucoma patients
Zhiying Ou, Guangjian Liu, Wenping Liu, Yehua Deng, Ling Zheng, Shu Zhang, Guangqiang Feng
Bioscience Reports. 2018; 38(4)
[Pubmed] | [DOI]
15 Research progress on human genes involved in the pathogenesis of glaucoma (Review)
Hong-Wei Wang, Peng Sun, Yao Chen, Li-Ping Jiang, Hui-Ping Wu, Wen Zhang, Feng Gao
Molecular Medicine Reports. 2018;
[Pubmed] | [DOI]
16 CYP1B1 and MYOC Mutations in Vietnamese Primary Congenital Glaucoma Patients
Tan Do,William Shei,Pham Thi Minh Chau,Doan Le Trang,Victor H.K. Yong,Xiao Yu Ng,Yue Ming Chen,Tin Aung,Eranga N. Vithana
Journal of Glaucoma. 2016; 25(5): e491
[Pubmed] | [DOI]
17 Genotype-Phenotype Correlation in Moroccan Patients With Primary Congenital Glaucoma
Amina Berraho,Aziza Serrou,Nabila Fritez,Abdessamad El Annas,Fatiha Bencherifa,Fatima Gaboun,Latifa Hilal
Journal of Glaucoma. 2015; 24(4): 297
[Pubmed] | [DOI]
18 Genotype/Phenotype Correlation in Primary Congenital Glaucoma Patients in the Lebanese Population: A Pilot Study
Christiane Al-Haddad,Marwan Abdulaal,Rebecca Badra,Anita Barikian,Bahaa Noureddine,Chantal Farra
Ophthalmic Genetics. 2014; : 1
[Pubmed] | [DOI]
19 CYP1B1 genotype influences the phenotype in primary congenital glaucoma and surgical treatment
X. Chen,Y. Chen,L. Wang,D. Jiang,W. Wang,M. Xia,L. Yu,X. Sun
British Journal of Ophthalmology. 2013;
[Pubmed] | [DOI]
20 CYP1B1, MYOC, and LTBP2 Mutations in Primary Congenital Glaucoma Patients in the United States
Sing-Hui Lim,Khanh-Nhat Tran-Viet,Tammy L. Yanovitch,Sharon F. Freedman,Thomas Klemm,Whitney Call,Caldwell Powell,Ajay Ravichandran,Ravikanth Metlapally,Erica B. Nading,Steve Rozen,Terri L. Young
American Journal of Ophthalmology. 2013; 155(3): 508
[Pubmed] | [DOI]
21 Screening of the LTBP2 gene in a north Indian population with primary congenital glaucoma
Mohanty, K. and Tanwar, M. and Dada, R. and Dada, T.
Molecular Vision. 2013; 19: 78-84
22 CYP1B1, MYOC, and LTBP2 mutations in primary congenital glaucoma patients in the United States
Lim, S.-H. and Tran-Viet, K.-N. and Yanovitch, T.L. and Freedman, S.F. and Klemm, T. and Call, W. and Powell, C. and Ravichandran, A. and Metlapally, R. and Nading, E.B. and Rozen, S. and Young, T.L.
American Journal of Ophthalmology. 2013; 155(3): 508-517
23 Ophthalmic genetics: Moving forward
Abu-Amero, K.K.
Middle East African Journal of Ophthalmology. 2011; 18(1): 1
24 Screening of CYP1B1 and LTBP2 genes in Saudi families with primary congenital glaucoma: Genotype-phenotype correlation
Abu-Amero, K.K. and Osman, E.A. and Mousa, A. and Wheeler, J. and Whigham, B. and Rand Allingham, R. and Hauser, M.A. and Al-Obeidan, S.A.
Molecular Vision. 2011; 17: 2911-2919


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

  In this article
    Prevalence of PC...
    Identification o...
    Article Tables

 Article Access Statistics
    PDF Downloaded447    
    Comments [Add]    
    Cited by others 24    

Recommend this journal