Primary Congenital Glaucoma Patients Research Articles

Intraocular pressure measurement by three different tonometers in primary congenital glaucoma.

Purpose:To determine the agreement between intraocular pressure (IOP) measurements using an automated non-contact tonometer (NCT), Goldmann applanation tonometer (GAT), and the ocular response analyzer (ORA) in subjects with primary congenital glaucoma (PCG).Methods:Twenty-nine eyes of 17 PCG patients underwent IOP measurements using NCT, GAT and ORA. Variables obtained by the ORA were corneal-compensated IOP (IOPcc), Goldmann-correlated IOP (IOPg), corneal hysteresis (CH), and corneal resistance factor (CRF). A difference more than 1.5 mmHg for IOP was considered as clinically relevant.Results:Mean age of the patients was 12 years. Mean IOP (±standard deviation, SD) was 15.3 ± 2.8 mmHg (GAT), 15.5 ± 6.0 (NCT), 19.2 ± 7.0 (IOPg), and 21.1 ± 7.9 (IOPcc); (P = 0.001). Except for NCT vs. GAT (P = 1.0), the average IOP difference between each pair of measurements was clinically relevant. The 95% limits of agreements were − 10.2 to 10.3 mmHg (NCT vs. GAT), −7.8 to 15.3 (IOPg vs. GAT), and − 8.1 to 19.0 (IOPcc vs. GAT). The differences in IOP measurements increased significantly with higher average IOP values (r = 0.715, P = 0.001, for NCT vs. GAT; r = 0.802, P < 0.001, for IOPg vs. GAT; and r = 0.806, P < 0.001, for IOPcc vs. GAT). CH showed a significant association with differences in IOP measurements only for IOPcc vs. GAT (r = 0.830, P < 0.001).Conclusion:Mean IOP obtained by NCT was not significantly different from that of GAT, but ORA measured IOPs were significantly higher than both other devices.

Mutation spectrum of CYP1B1 in Chinese patients with primary open-angle glaucoma

PurposeThe CYP1B1 gene has been shown to be related to primary open-angle glaucoma (POAG). This study aimed to identify the mutation profile of CYP1B1 in Chinese individuals with POAG.MethodsThe study...

CYP1B1 mutations in patients with primary congenital glaucoma from Saudi Arabia.

BackgroundCYP1B1 is the most commonly mutated gene in primary congenital glaucoma (PCG). This study was undertaken to identify mutations in CYP1B1 in the Western region of Saudi Arabia.MethodsBlood of patients who had typical findings of PCG, were screened by direct sequencing of all coding exons and splice junctions of the CYP1B1 gene.Results34 patients were studied; 18 patients belonged to 8 families, and 16 patients were non-familial, isolated PCG. Consanguinity was found in 27/34 (79.4%) of cases. All patients were diagnosed to have bilateral PCG at birth except one child, who had glaucoma in the right eye. More males (61.8%) were affected than females (38.2%). 79.4% (27/34) of patients were solved with pathogenic mutations and 20.6% (7/34) remained unsolved. Of the solved ones, 22.2% (6/27) of patients carry a pathogenic allele on one allele while the other allele remained yet to be determined. Direct sequencing of exon 2 revealed two pathogenic variants (p.Gly61Glu, p.Glu229Lys). P.Gly61Glu substitution was found both homozygously in 63% (17/27) of cases, and heterozygously in one patient. P.Glu229Lys variant was found heterozygous in 3.7% (1/27) of cases. One pathogenic variant (p.Arg469Trp) was found in exon 3, and is present homozygously in 14.8% (4/27) of cases while four patients have this variant heterozygously. All mutations were reported previously in the Saudi population, except p.Glu229Lys. Severe cases were associated with p.Gly61Glu, and p.Arg469Trp in 50% and 30% of ten patients respectively.ConclusionsThis study confirms that CYP1B1 mutations are the most frequent cause of PCG in the Saudi population, with p.Gly61Glu being the major disease-associated mutation. P.Glu229Lys is a newly discovered mutation in our PCG patients. Patient lacking mutation in CYP1B1 gene seems likely, to have another genetic loci involved in the pathogenesis of the disease, and need further study. Genetic studies of recessive diseases such as PCG is important in consanguineous populations, since it will increase awareness and allows genetic counseling to be offered to patients and their relatives. This will not only reduce the disease to be inherited to future generations, but will also reduce the disease burden in the community.

Identification of novel CYP1B1 gene mutations in patients with primary congenital and primary open-angle glaucoma.

CYP1B1 is the most commonly mutated gene in primary congenital glaucoma (PCG), and mutations have also been identified in primary open-angle glaucoma (POAG). This study was undertaken to describe mutations in CYP1B1 in patients and families with PCG and POAG from Pakistan. Case-control series. Forty families, 190 sporadic POAG cases and 140 controls from Pakistan. Patients and healthy individuals of one consanguineous Pakistani family were genotyped with high-resolution single nucleotide polymorphism microarrays. Homozygosity mapping was performed using HomozygosityMapper. Direct sequencing of CYP1B1 gene was performed in probands of the families, sporadic POAG cases and control individuals. Mutations in the CYP1B1 gene in PCG and POAG patients. Homozygosity mapping in a consanguineous Pakistani family revealed one 11-Mb homozygous region encompassing the CYP1B1 gene. A homozygous CYP1B1 missense mutation (p.Arg390His) was identified in this family. Sequence analysis of CYP1B1 in 39 additional families revealed one known and three novel homozygous mutations in PCG (p.Ala288Pro, p.Asp242Ala, p.Arg355* and p.Arg290Profs*37). In POAG, one novel heterozygous missense mutation (p.Asp316Val) was identified in one family and a previously reported mutation (p.Glu229Lys) was identified in three families. Analysis of CYP1B1 in a panel of 190 sporadic POAG patients revealed three novel heterozygous variants (p.Thr234Lys, p.Ala287Pro and p.Gln362*) and three previously reported heterozygous variants (p.Gly61Glu, p.Glu229Lys and p.Arg368His). The p.Glu229Lys variant was significantly associated with POAG (P = 0.03; odds ratio 2.49). This study confirms that CYP1B1 mutations are associated with POAG and PCG in the Pakistani population.

CYP1B1 gene mutations causing primary congenital glaucoma in Tunisia.

Primary congenital glaucoma (PCG) is responsible for a significant proportion of childhood blindness in Tunisia. Early prevention based on genetic diagnosis is therefore required. This study sought to determine the frequency of CYP1B1 (cytochrome P450, family 1, subfamily B, polypeptide 1) mutations in 18 PCG patients, recruited from Central and Southern of Tunisia. Genomic DNA was extracted and the coding regions of CYP1B1 were analysed by direct sequencing. A phylogenetic network of CYP1B1 haplotypes was drawn using the median-joining algorithm. Sequence analysis revealed a "tetra-allelic mutation" (two novel mutations, p.F231I and p.P437A in the homozygous state) in one patient. The healthy members of his family carried those variations on the same allele. Two previously described mutations p.G61E and c.535delG were also identified in the homozygous state in seven and two probands, respectively. Seven single-nucleotide polymorphisms were identified and used to generate haplotypes. Our results showed that the CYP1B1 mutations were present in 55% of Tunisian PCG patients' alleles. Haplotype analysis allowed us to define the proto-haplotype and to confirm historical migratory flows. Establishment of PCG genetic aetiology in Tunisia will improve genetic diagnosis and counselling.

Identification of missing genetic variants in primary congenital glaucoma (776.8)

Background and Objective: Variations in the cytochrome P450, family 1, subfamily B, polypeptide 1 (CYP1B1) gene and mutations in the latent transforming growth factor beta binding protein 2 (LTBP2) gene cause autosomal recessive Primary Congenital Glaucoma (PCG). However, in India, only 45% of PCG patients harbor alterations in the CYP1B1 gene. The present study aimed to identify novel genetic variations contributing to unexplained PCG cases in India.Methods: 112 unrelated Indian PCG patients in whom neither chromosome carried a CYP1B1 or an LTBP2 mutation, and 106 matched controls, were recruited for this study. DNA isolated from each case and control was screened for a total of 906,600 single nucleotide polymorphism (SNP) loci using an Affymetrix 6.0 whole genome genotyping array. The marker data were first used for an association analysis followed by multiple test corrections, after an initial adjustment for population stratification. A second approach undertaken in this study was detection of regions of homozygosity (ROH) across all autosomes that are significantly found more often in cases than in normal controls.Results: Eleven SNPs in 5 genes and intergenic regions showed statistically significant association with PCG. These genes are neuronal growth regulator 1 (NEGR1) [1p31.1], glutamate receptor, ionotropic, kainate 4 (GRIK4) [11q22.3], plexin domain containing 2 (PLXDC2) [10p12.31], YY1 associated factor 2 (YAF2) [12q12] and copine IV (CPNE4) [3q22.1]. The results of the ROH analysis have indicated the presence of two regions of homozygosity that cover two important genes, namely kelch‐like family member 26 (KLHL26) [19p13.11] and teashirt zinc finger homeobox 2 (TSHZ2) [20q13.2].Conclusions: The present study has identified likely locations of new putative genes underlying PCG. These genes have previously not been associated with any type of glaucoma, but the products of these genes appear to be involved in pathways related to eye development and physiology.Grant Funding Source: Department of Biotechnology

Corneal sensitivity and morphology of the corneal subbasal nerve plexus in primary congenital glaucoma

To quantify the corneal subbasal nerve density and the total number of nerve fibers in primary congenital glaucoma (PCG) and to evaluate their impact on corneal sensitivity. Forty eyes of 26 PCG patients were compared with 40 eyes randomly selected from 40 non-glaucoma patients who populated the control group. Central corneal sensitivity (CCS) was assessed by means of Cochet-Bonnet esthesiometry. The mean subbasal nerve density and the total number of nerve fibers were quantified by laser-scanning confocal microscopy. Normality of data was assessed by Kolmogorov-Smirnov testing. Differences in parameters were assessed with Student's t-test, while correlations with CSS were assessed with Pearson's correlation. Significant differences were identified in the mean subbasal nerve density (2108 ± 692 μm in PCG, 2642 ± 484 μm in controls, P = 0.003) and in the total number of nerve fibers (12.3 ± 4.2 in PCG, 15.4 ± 3.1 in controls, P = 0.02). Both groups presented comparable mean CCS and tortuosity. Both groups presented strong correlations between CCS and mean nerve density (r = 0.57 in PCG, r = 0.67 in controls, all P < 0.05), and between CCS and total number of nerve fibers (r = 0.55 in PCG, r = 0.56 in controls, all P < 0.05). PCG exerts significant changes in both the mean subbasal nerve density and the total number of nerve fibers. However, these changes do not appear to affect central corneal sensitivity.

A retrospective and consecutive study of viscocanalostomy versus trabeculectomy for primary congenital glaucoma

Background Surgical interventions are the main treatment for primary congenital glaucoma (PCG). This study aimed to compare the efficacy and safety between viscocanalostomy and mitomycin C (MMC)-trabeculectomy in patients with PCG. Methods A total number of 43 patients with PCG who underwent either viscocanalostomy (group 1) or MMC- trabeculectomy (group 2) between June 2003 and June 2008 were retrospectively reviewed. The patients' intraocular pressures (IOPs) were examined before surgery and on day 1, week 1, month 1, month 6, and month 12 post-operative. Mean horizontal corneal diameters, success rates, intra- and post-operative complications were compared between the two groups. Results Pre-operative IOPs were (31.96±3.90) mmHg in group 1 and (32.56±4.00) mmHg in group 2. At the last visit, IOPs were (16.78±2.20) mmHg and (15.77±2.60) mmHg, respectively (P &lt;0.001); the complete success rates of group 1 and group 2 were 45.9% and 67.4%, respectively, and the difference was not statistically significant (P=0.158). There were no major complications occurred in the two groups. Conclusions Both viscocanalostomy and trabeculectomy can lower IOP in PCG patients effectively. Although there was no major complications occurred in both groups, viscocanlostomy may decrease the probability of postoperative haemorrhage, hypotony, cataract, or choroid effusion.

Primary and Secondary Congenital Glaucoma: Baseline Features From a Registry at King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia

To compare the demographic and clinical distribution of primary and secondary congenital glaucoma from a registry at King Khaled Eye Specialist Hospital. Registry-based cohort study. Review of registry data that included new patients with congenital glaucoma seen between 2001 and 2003 (29 months); analysis of the demographic data and clinical features of primary and secondary congenital glaucoma at presentation. A total of 325 eyes of 180 patients were included. Most patients had primary congenital glaucoma (80%). The mean (± SD) age at presentation for primary congenital glaucoma was 3.8 ± 10.7 months and for secondary congenital glaucoma was 4.3 ± 7.9 months. Most primary congenital glaucoma and secondary congenital glaucoma patients had bilateral disease (82.6%; 74.3%). Primary congenital glaucoma was equally distributed by sex but secondary congenital glaucoma was 1.5-fold more common in male patients. A positive family history was elicited in 30%, and almost 60% had a history of consanguinity in both groups. The mean intraocular pressure and corneal diameter were comparable in both groups but the axial length was significantly longer in primary congenital glaucoma and cup-to-disc (C/D) ratio greater in secondary congenital glaucoma. In the primary congenital glaucoma group, corneal haze showed a significant relationship with most clinical parameters. In primary congenital glaucoma, a positive correlation was noted between age at presentation and increasing corneal diameter and axial length but a negative relationship was noted with C/D ratio and corneal haze, whereas for secondary congenital glaucoma only axial length was positively correlated. The congenital glaucoma registry provides unique baseline data on primary congenital glaucoma and secondary congenital glaucoma in Saudi Arabia that will enable us to better understand the disease in the Kingdom and region.

CYP1B1, MYOC, and LTBP2 Mutations in Primary Congenital Glaucoma Patients in the United States

To screen primary congenital glaucoma patients in the United States for sequence variants within the CYP1B1, LTBP2, and MYOC genes using Sanger and whole exome sequencing. Retrospective case-control study. Fifty-seven primary congenital glaucoma patients (47 families), 71 unaffected family members of the primary congenital glaucoma probands, and 101 healthy unrelated individuals were recruited from a single institution. Sanger sequencing of the primary congenital glaucoma gene, CYP1B1, was performed on 47 proband deoxyribonucleic acid samples. Simultaneously, whole exome sequencing was conducted on 3 families, each including more than 1 affected individual. Concurrently, 33 of 47 primary congenital glaucoma probands with extended family deoxyribonucleic acid samples were screened for LTBP2 and MYOC gene mutations. Exome-sequenced variations were validated by additional Sanger sequencing to confirm segregation of filtered disease-causing single nucleotide variations. Seven primary congenital glaucoma families (14.9%) manifested disease phenotypes attributable to CYP1B1 mutations. One primary congenital glaucoma family possessed homozygous mutant alleles, whereas 6 families carried compound heterozygous mutations. Five novel combinations of compound heterozygous mutations were identified, of which 2 combinations were found with whole exome sequencing. No disease-causing mutations within the LTBP2 and MYOC genes were discovered. This study analyzed CYP1B1, LTBP2, and MYOC mutations in a cohort of primary congenital glaucoma patients from the United States, applying whole exome sequencing as a complementary tool to Sanger sequencing. Whole exome sequencing, coupled with Sanger sequencing, may identify novel genes in primary congenital glaucoma patients who have no mutations in known primary congenital glaucoma genes.

A clinical and molecular genetics study of primary congenital glaucoma in South Korea

ObjectivesTo investigate the clinical manifestations associated with the mutation spectrums of the human cytochrome P450 (CYP1B1) and myocilin (MYOC) genes in South Korean patients with primary congenital glaucoma (PCG).MethodsEighty-five unrelated...

Comparison of dynamic contour tonometry and Goldmann applanation tonometry in relation to central corneal thickness in primary congenital glaucoma

To compare intraocular pressure (IOP) measurements obtained with dynamic contour tonometer (DCT) and Goldmann applanation tonometer (GAT), and to investigate their relationship to central corneal thickness (CCT) in primary congenital glaucoma (PCG) eyes. Thirty-one eyes of 31 PCG patients (25.7 ± 7.2 years old) were examined. PCG was defined as elevated IOP, enlarged corneal diameter (buphthalmos), Haab's striae and abnormal findings at gonioscopy. The mean of three measurements of GAT, DCT (quality scores 1 and 2), and CCT were obtained and assessed for agreement by means of Bland-Altman plot and for Spearman correlation test. Mean CCT was 534 ± 72.3 μm (range: 430 to 610 μm). Mean IOP measurements were 15.1 ± 4.2 mmHg (range: 5.5 to 22.7 mmHg) for DCT and 14.5 ± 5.6 mmHg (range: 7.0 to 34.0 mmHg) for GAT (P = 0.244). Spearman correlation tests showed that IOP difference (DCT - GAT) was not correlated with CCT (r (2) = 0.023, P = 0.417). IOP measurements by DCT were weakly but statistically correlated with those obtained with GAT (r(2) = 0.213, P = 0.0089). Bland-Altman analysis revealed poor agreement between DCT and GAT readings, considering the 95 % confidence intervals of ± 10.45 mmHg. The differences between DCT and GAT readings were not influenced by CCT in this series of patients. Considering the weak correlation and the poor agreement observed between GAT and DCT measurements and that they both may be affected by corneal biomechanical changes, these methods should not be used interchangeably, and may possibly give no meaningful IOP values in PCG patients.

Genotype/Phenotype Correlation in Primary Congenital Glaucoma Patients From Different Ethnic Groups of the Israeli Population

To investigate the roles of CYP1B1 and MYOC mutations and characterize the phenotype of primary congenital glaucoma in Israeli patients from 3 different ethnic backgrounds. Interventional case series. This institutional study included 34 Israeli primary congenital glaucoma patients (26 families) comprising 9 Jews (9 families), 17 non-Bedouin Muslim Arabs (10 families), and 8 Druze (7 families). The patients and their relatives (n = 99) were screened for CYP1B1 and MYOC mutations. Mutations in the CYP1B1 gene were detected in 12 of 26 families (46%) with primary congenital glaucoma (5 Muslim Arab, 5 Druze, and 2 Jewish). The Jewish families had compound heterozygous mutations and digenic mutations (ie, an Ashkenazi family had mutations in the CYP1B1 gene [Arg368His, R48G, A119S, and L432V haplotypes] and an Ashkenazi-Sephardic family had a mutation on the CYP1B1 gene [1908delA, Sephardic] with a second missense mutation on the MYOC gene [R76K, Ashkenazi]). The Muslim Arabs and Druze tended to have a more severe phenotype than that of the Jews. The phenotype and spectrum of the CYP1B1 and MYOC mutation roles in the clinical characteristics of primary congenital glaucoma varied according to ethnicity. The rarity of mutations in the CYP1B1 gene among Ashkenazi primary congenital glaucoma patients indicates that a different locus may be involved in the phenotype.

Identification of novel disease gene for primary congenital glaucoma (PCG) through homozygosity mapping and next‐generation sequencing strategies in a large consanguineous pedigree

Abstract Purpose Primary congenital glaucoma (PCG) is caused by developmental anomalies of the trabecular meshwork and the anterior chamber angle resulting in an increased ocular pressure (IOP) and optic nerve damage. In general PCG displays an autosomal recessive inheritance pattern and is genetically heterogeneous. To date, three PCG loci are known, namely GLC3A, GLC3B and GLC3C, and two causal genes have been identified, CYP1B1 located in the GLC3A locus and LTPB2 located at 1.3 MB proximal to the GLC3C locus. The purpose of the current study is to identify the causal disease gene in a large consanguineous family with PCG, originating from Jordany. CYP1B1 mutations and linkage to the LTBP2, GLCB3 and GLCC3 locus were previously excluded. Methods In a first step, DNA from members from the consanguineous family will be genotyped by 250K GeneChip Mapping Affymetrix arrays. Homozygosity mapping will be applied to identify potential disease loci, using a homemade Perl script. Next, microsatellite analysis will be performed in order to confirm findings and to narrow down candidate regions. Subsequently, candidate regions of interest will be captured (Agilent) and sequenced on the Illumina Genome Analyser IIx (GAIIx). Gene and variant prioritization will be done using in‐house developed software, followed by segregation analysis and screening in control individuals. At last, a cohort of 30 molecularly unsolved PCG patients will be screened for mutations in the newly identified disease. Conclusion The identification of a new disease gene for PCG may lead to better insights into the molecular pathogenesis of glaucoma, and might uncover novel therapeutic strategies.

CYP1B1 Gene Analysis in Primary Congenital Glaucoma Brazilian Patients

To determine the spectrum of CYP1B1 gene mutations in Brazilian patients with primary congenital glaucoma, and to correlate the presence of alterations in the CYP1B1 gene sequence with clinical aspects of the disease. Thirty nonrelated patients with primary congenital glaucoma were studied. Molecular analysis consisted of the codifying region sequencing (exons 2 and 3) and intron/exon boundaries. CYP1B1 gene mutations were present in 9 (30%) of the 30 patients. The structural changes in the CYP1B1 gene previously described in the literature and observed in our study were Q19X, P437L, A443G, g.4340delG, g.7901_79013delGAGTGCAGGCAGA, g.8182delG, and g.8214_8215delG. Three new mutations were observed: 4635delT, 4523delC, and L378Q, in addition to 3793T→C, R48G, A119S, L432V, D449D, and N453S polymorphisms. Patients carrying CYP1B1 gene mutations needed more surgical procedures to control intraocular pressure, either when both eyes were evaluated (P=0.003) or when the worst eye of the patient was analyzed (P=0.011). In relation to the number of affected eyes, all patients with mutations (n=9/9) developed bilateral glaucoma, whereas 11/21 patients without mutations in the CYP1B1 gene had bilateral glaucoma (P=0.013). In this group of primary congenital glaucoma patients, a 30% mutation frequency in the CYP1B1 gene was observed. The presence of mutations was associated with a more severe form of the disease, requiring more surgeries for intraocular pressure control and with a higher rate of bilateral cases.

Mutation spectrum of the CYP1B1 gene for congenital glaucoma in the Japanese population

Mutations of the CYP1B1 gene cause primary congenital glaucoma (PCG), Peters anomaly, and juvenile open-angle glaucoma (JOAG). The aim of this study was to determine the spectrum and role of the CYP1B1 gene in Japanese patients with PCG or JOAG. Genomic DNA was extracted from the leukocytes of 18 unrelated patients with PCG and 21 unrelated patients with JOAG. All of the patients developed high intraocular pressure (IOP) before the age of 35 years. One hundred unrelated healthy adults with normal IOP were examined in the same way. The three exons of the CYP1B1 gene were amplified by polymerase chain reaction and directly sequenced. Mutational screening and sequence analyses of the CYP1B1 gene revealed four mutations in four patients with PCG: p.Asp192Val, c.4776insAT, p.Val364Met, and p.Asp430Glu. The first three mutations have been reported in other Japanese PCG patients, but Asp430Glu is a new mutation. No mutations were found in the CYP1B1 gene of the JOAG patients. PCG in approximately 20% of Japanese patients may be associated with CYP1B1 mutations, but JOAG is not. The three mutations p.Asp192Val, c.4776insAT, and p.Val364Met appear to be common in the Japanese population and might be useful in genetic screening for PCG.

Genetic variants of CYP1B1 and WDR36 in the patients with primary congenital glaucoma and primary open angle glaucoma from saint-Petersburg

In 32 patients with primary congenital glaucoma (PCG), a search for mutations in the myocilin (MYOC), cytochrome P450B1 (CYP1B1), and WDR36 genes was performed. The Q368X mutation in myocilin gene, typical of the patients with adult-onset primary open-angle glaucoma (POAG), was not detected in the PCG patients. Screening of the CYP1B1 introns 2 and 3 for the presence of mutations in PCG patients revealed only six DNA polymorphisms, including IVS1-12ntT>C (g.3793 T>C), A119S (g.4160 G>T; GCC>TCC), G188G (g.4369 C>A; GGC>GGA), L432V (G.8131 C>G; CTG>GTG), D449D (g.8184 C>T; GAC>GAT), and N453S (g.8195 A>G; AAC>AGC) (nucleotide numbering is given in accordance with the GenBank sequence U56438). In the groups of PCG patients and donors without eye diseases, the frequencies of these variants were not statistically significantly different, pointing to the neutrality of these polymorphisms. Furthermore, the CYP1B1 polymorphism L432V, considered to be associated with POAG in some world populations, was not associated with this disease in the patients from St. Petersburg. DNA collections obtained from the POAG and PCG patients and from the control group were tested for the carriage of the worldwide distributed mutations of the WRD36 gene, D658G, R529Q, A449T, and N355S. D658G variant was found with equally low frequencies in the groups of POAG and PCG patients, as well as in the control group. Mutations A449T and R529Q were found only once each, while mutation N355S was not detected in any of the groups examined. Our results indicate that the WDR36 variants make no substantial contribution to the development of POAG and PCG in the patients from St. Petersburg and represent normal DNA polymorphism. It is likely that in most of the PCG patients from the population examined the disease is not associated with the CYP1B1 gene defects.

A novel mutation of CYP1B1 gene in primary congenital glaucoma

To investigate the distribution of the CYP1B1 (Cytochrome P450, family 1, subfamily B, polypeptide 1) gene mutations in primary congenital glaucoma (PCG) in Hunan Province. Case-control study. Thirteen cases of PCG from different districts of Hunan province were collected in this study. Direct sequencing was used to evaluate the coding and the promoter regions of the CYP1B1 gene in PCG patients. A novel pathogenic mutation (c.C319G, L107V) was identified in a PCG patient in our study and it was a missense mutation in exon 2. Additionally, four single nucleotide polymorphisms(SNPs) were found in PCG patients, including R48G, A119S, V432L and D449D. A novel CYP1B1 gene mutation (L107V) may be the cause for primary congenital glaucoma in Hunan Province.

Quality of life in patients with primary congenital glaucoma following antiglaucoma surgical management

To evaluate the 23-item scale of Quality of Life (QOL) for patients with primary congenital glaucoma (PCG). It was a cross-sectional study. The QOL scale specific for patients with PCG was firstly evaluated on 51 patients with PCG following antiglaucoma surgery at last followup visit (7.80 years +/- 2.93 years with a median at 7 years) and 50 participants with normal visual acuity (VA) as control. All participants were aged 5-20 years old. The QOL of PCG was evaluated with type of disease, severity, surgical outcome, postoperative VA, age, gender and personality by using single-factor correlation analysis and multiple-factor stepwise regression analysis. The PCG-QOL scale achieved good reliability, validity and responsibility for PCG and 23-item were all qualified for QOL evaluation of PCG. The total scores of QOL in patients with PCG were significantly lower than those of normal individuals (PCG 60.22 +/- 10.02,normal individuals 71.41 +/- 10.11; t = 5.682, P = 0.000). Single-factor correlation analysis showed that the total scores of QOL were associated significantly with the severity of glaucoma (F = 24.026, P = 0.000), surgical outcome (t = 2.638, P = 0.009) and postoperative VA (F = 11.248, P = 0.000); The visual function scores were associated significantly with the severity (F = 12.677, P = 0.000) and postoperative VA (F = 10.369, P = 0.000). The self-care ability scores were associated significantly with the severity (F = 11.064, P = 0.000) and surgical outcome (t = 2.297, P = 0.042). The social and mental scores were all correlated significantly with the severity (F = 6.869, P = 0.020; F = 5.721, P = 0.019) and personality (t = 4.352, P = 0.009; t = 2.297, P = 0.042). Multiple-factor stepwise regression analysis showed that there were significant correlations between total scores and the severity (P3 = -6.985, P = 0.001), postoperative VA (beta = -4.978, P = 0.003) and personality (13 = -5.201, P = 0.020). The PCG-QOL scale could be used for evaluating the QOL of PCG patients aged 5-20 years. The main factors that influence on the QOL of patients with PCG are severity of the disease, postoperative VA and personality. Preventing progression of glaucoma, improving VA and giving right psychological guidance may improve the QOL of patients with PCG.

A Clinical and Molecular Genetic Study of German Patients with Primary Congenital Glaucoma

To estimate an accurate incidence rate for CYP1B1 mutations in German patients with primary congenital glaucoma (PCG). Observational case series. Blood was obtained from 39 unrelated patients of German origin with clear clinical features of PCG and screened for mutations in the CYP1B1 gene using direct deoxyribonucleic acid sequencing. One hundred ethnically matched control subjects were screened for novel sequence variants using restriction fragment length polymorphism and denaturing high-performance liquid chromatography. Sequence analysis identified 11 different mutations in 7 patients (18%). Four patients were compound heterozygotes, 2 subjects heterozygous, and 1 homozygous for CYP1B1 mutations. One deletion (c.199_206del8) and 3 missense mutations (L177P, F190L, and S282N) were novel. None of the novel missense mutations identified was found in normal controls. Our results indicate that only a minor proportion of German PCG patients harbor mutations in the CYP1B1 gene and are in line with similar studies from other ethnic populations in which the rate of consanguinity is low. In addition, this is the first report discussing the phenotypes of German PCG patients with and without CYP1B1 mutations.