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

BMC Ophthalmology

Research Article

Alia M Albalawi¹  Sulman Basit¹  Muhammad Latif¹  Mohammed I. Samman¹  Abdulrahman Badawi²  Mohammed Abu Sayf²  Ma’an Abdullah Al-Barry³  Sibtain Afzal⁴ 

[1] Center for Genetics and Inherited Diseases, Taibah University Almadinah Almunawarah, 30001, Medina, Kingdom of Saudi Arabia;College of Medicine, Taibah University Almadinah Almunawarah, Medina, Kingdom of Saudi Arabia;College of Medicine, Taibah University Almadinah Almunawarah, Medina, Kingdom of Saudi Arabia;Magribi Hospital, Almadinah Almunawarah, Medina, Kingdom of Saudi Arabia;Prince Naif Center for Immunology Research, College of Medicine, King Saud University, 11472, Riyadh, Saudi Arabia;

关键词: Vogt-Koyanagi-Harada;    Vitamin D;    Genes;    Mutations;   

DOI  :  10.1186/s12886-016-0354-6

 received in 2016-04-21, accepted in 2016-09-27,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundVKH 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.MethodsGenomic 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.ResultsVitamin 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.ConclusionsScreening 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.

【 授权许可】

CC BY   
© The Author(s). 2016