Dataset Information

Sequence analysis of four vitamin D family genes (VDR, CYP24A1, CYP27B1 and CYP2R1) in Vogt-Koyanagi-Harada (VKH) patients: identification of a potentially pathogenic variant in CYP2R1.

ABSTRACT: BACKGROUND:VKH is a rare autoimmune disease. Decreased level of vitamin D has recently been found to be involved in the pathogenesis of Vogt-Koyanagi-Harada (VKH) disease. This study was designed to screen the vitamin D pathway genes for pathogenic mutations, if any, in VKH patients. METHODS:Genomic DNA was extracted from blood samples collected from patients with VKH disease and healthy controls. Entire coding region, exon-intron junctions of four genes were sequenced in DNA from 39 Saudi VKH patients and 50 ethnically matched healthy individuals. All patients and controls were unrelated. RESULTS:Vitamin D levels in VKH patients were found either insufficient (21-29 ng/mL) or deficient (<20 ng/mL). Sequencing analysis of the VDR, CYP24A1, CYP27B1 and CYP2R1 detected twelve nucleotide changes in these genes in our cohort of 39 patients; 4 of which were non-coding, 6 were synonymous coding and 2 were non-synonymous coding sequence changes. All synonymous coding variants were benign polymorphisms with no apparent clinical significance. A non-synonymous coding sequence variant (c.2 T?>?C; p.1Met?) found in VDR is an initiation coding change and was detected in control individuals as well, while another variant (c.852G?>?A; p.284 M?>?I) found in CYP2R1 is predicted to be disease causing by mutationtaster software. This potentially pathogenic variant was found in 17 out of 39 VKH patients. CONCLUSIONS:Screening of four Vitamin D pathway genes in 39 VKH patients shows that a potentially pathogenic sequence variant in CYP2R1 may cause VKH in a subset of patients. These findings support the previous observation that low vitamin D levels might play a role in VKH pathogenesis and mutations in genes involved in vitamin D anabolism and catabolism might be of importance in VKH pathobiology.

SUBMITTER: Al-Barry MA

PROVIDER: S-EPMC5050582 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Sequence analysis of four vitamin D family genes (VDR, CYP24A1, CYP27B1 and CYP2R1) in Vogt-Koyanagi-Harada (VKH) patients: identification of a potentially pathogenic variant in CYP2R1.

Al-Barry Ma'an Abdullah MA Albalawi Alia M AM Sayf Mohammed Abu MA Badawi Abdulrahman A Afzal Sibtain S Latif Muhammad M Samman Mohammed I MI Basit Sulman S

BMC ophthalmology 20161004 1

<h4>Background</h4>VKH is a rare autoimmune disease. Decreased level of vitamin D has recently been found to be involved in the pathogenesis of Vogt-Koyanagi-Harada (VKH) disease. This study was designed to screen the vitamin D pathway genes for pathogenic mutations, if any, in VKH patients.<h4>Methods</h4>Genomic DNA was extracted from blood samples collected from patients with VKH disease and healthy controls. Entire coding region, exon-intron junctions of four genes were sequenced in DNA from ...[more]

PMID: 27716192

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Project description:ImportanceTo our knowledge, a set of well-defined diagnostic criteria is not yet developed for the diagnosis of Vogt-Koyanagi-Harada (VKH) disease.ObjectiveTo develop and evaluate a set of diagnostic criteria for VKH disease using data from Chinese patients.Design, setting, and participantsThis case-control study reviewed medical records of patients from a tertiary referral center between October 2011 and October 2016. Data from 634 patients with VKH disease and 623 patients with non-VKH uveitis from southern China were used to develop the Diagnostic Criteria for VKH Disease (DCV). Data from an additional group of 537 patients with a definite VKH disease diagnosis and 525 patients with non-VKH uveitis from northern China were used to evaluate the diagnostic criteria.Main outcomes and measuresSensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and receiver operating characteristic.ResultsOf the 1257 patients used to construct the DCV, 665 (52.9%) were male, and the mean (SD) age at disease onset was 38.6 (13.6) years. The 3-class model and 21 clinical findings were selected by latent class analysis. Variables with a high positive rate in the early-phase or late-phase VKH group or high specificity constituted essential parameters. Constellations of these essential parameters constructed the DCV. The sensitivity and NPV of the DCV were higher than those of the Revised Diagnostic Criteria for VKH Disease (RDC) (sensitivity: 94.6% vs 71.9%; difference, 22.7%; 95% CI, 18.5-27.0; NPV: 94.3% vs 76.6%; difference, 17.7%; 95% CI, 13.9-21.5). The specificity and PPV of the DCV were not different from that of the RDC (specificity: 92.2% vs 93.9%; difference, 1.7%; 95% CI, -1.4 to 4.8; PPV: 89.3% vs 92.3%; difference, 3.0%; 95% CI, -1.4 to 4.8). The area under the receiver operating characteristic curve of the DCV and the RDC were 0.934 (95% CI, 0.917-0.951) and 0.829 (95% CI, 0.803-0.855), respectively.Conclusions and relevanceThe DCV were developed and evaluated using data from Chinese patients with VKH disease and showed a high sensitivity, NPV, and area under the receiver operating characteristic curve in comparison with the RDC. However, they were developed using a retrospective analysis and should be evaluated in prospective studies in other racial/ethnic populations.

Dataset Information

Sequence analysis of four vitamin D family genes (VDR, CYP24A1, CYP27B1 and CYP2R1) in Vogt-Koyanagi-Harada (VKH) patients: identification of a potentially pathogenic variant in CYP2R1.

Publications

Sequence analysis of four vitamin D family genes (VDR, CYP24A1, CYP27B1 and CYP2R1) in Vogt-Koyanagi-Harada (VKH) patients: identification of a potentially pathogenic variant in CYP2R1.

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