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:: Volume 8, Issue 3 (Int J Mol Cell Med 2019) ::
Int J Mol Cell Med 2019, 8(3): 179-190 Back to browse issues page
Identification of PROS1 as a Novel Candidate Gene for Juvenile Retinitis Pigmentosa
Ata Bushehri1, Davood Zare-abdollahi1, Afagh Alavi1, Alireza Dehghani2, Mohammadreza Mousavi-mircala3, Hamid Reza Khorram Khorshid 4
1- Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
2- Department of Ophthalmology, Eye Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
3- Department of Ophthalmology, Tabriz University of Medical Sciences, Tabriz, Iran.
4- Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran. , hhhkhkh@yahoo.com
Abstract:   (1164 Views)
Homozygous mutations of PROS1, encoding vitamin K-dependent protein S (PS), have been reported so far to be associated with purpura fulminans, a characteristic fatal venous thromboembolic disorder. The current work for the first time reports the clinical phenotype in patients with juvenile retinitis pigmentosa harboring a novel likely pathogenic variant in thePROS1 gene. Whole-exome sequencing was performed on the probands of a cohort with inherited retinal disease. Detailed phenotyping was performed, including clinical evaluation, electroretinography, fundus photography and spectral-domain optical coherence tomography. Analysis of whole-exome and Sanger sequencing led to the identification of a homozygous missense substitution (c.G122C:p.R41P) in PROS1 in affected individuals from two unrelated consanguineous families of Persian origin which had classic retinitis pigmentosa with no history of the venous thromboembolic disorder. This variant was segregated, fully congruous with the phenotype in all family members. Consistently, none of 1000 unrelated healthy individuals from the same population carried the mentioned variant, according to the Iranian national genome database (Iranome) and additional in-house exome control data. This study provides inaugural clinical traces for different roles of PS as a ligand for TAM receptor-mediated efferocytosis at the retinal pigmented epithelium; the R41P variant may affect proper folding of PS needed for γ-carboxylation and extra-cellular secretion. That conformational change may also lead to defective apoptotic cell phagocytosis resulting in postnatal degeneration of photoreceptors.
Keywords: Retinitis pigmentosa, RP, PROS1, protein S, TAM receptor, efferocytosis, apoptosis
Full-Text [PDF 391 kb]   (171 Downloads)    
Type of Study: Original Article | Subject: Genetics & Disease
Received: 2019/06/4 | Accepted: 2019/12/15 | Published: 2020/04/26
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Bushehri A, Zare-abdollahi D, Alavi A, Dehghani A, Mousavi-mircala M, Khorram Khorshid H R. Identification of PROS1 as a Novel Candidate Gene for Juvenile Retinitis Pigmentosa. Int J Mol Cell Med. 2019; 8 (3) :179-190
URL: http://ijmcmed.org/article-1-1102-en.html


Volume 8, Issue 3 (Int J Mol Cell Med 2019) Back to browse issues page
International Journal of Molecular and Cellular Medicine (IJMCM) International Journal of Molecular and Cellular Medicine (IJMCM)
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