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Identification of Reln Variant P.(Ser2486gly) in an Iranian Family With Ankylosing Spondylitis; the First Association of Reln and As Publisher Pubmed



Garshasbi M1 ; Mahmoudi M2, 3 ; Razmara E1 ; Vojdanian M2, 3 ; Aslani S2 ; Farhadi E2, 3 ; Jensen LR4, 5 ; Arzaghi SM6 ; Poursani S2, 3 ; Bitaraf A7 ; Eidi M1 ; Gharehdaghi EE1 ; Kuss AW4 ; Jamshidi A2, 3
Authors
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Authors Affiliations
  1. 1. Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, 14115-111, Iran
  2. 2. Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Inflammation Research Center, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany
  5. 5. Interfaculty Institute of Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany
  6. 6. Elderly Health Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
  7. 7. Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran

Source: European Journal of Human Genetics Published:2020


Abstract

Ankylosing spondylitis (AS) is a common complex inflammatory disease; however, up to now distinct genes with monogenic pattern have not been reported for this disease. In the present study, we report a large Iranian family with several affected members with AS. DNAs of the three affected and two healthy cases were chosen for performing whole-exome sequencing (WES). After several filtering steps, candidate variants in the following genes were detected: RELN, DNMT1, TAF4β, MUC16, DLG2, and FAM208. However, segregation analysis confirmed the association of only one variant, c.7456A>G; p.(Ser2486Gly) in the RELN gene with AS in this family. In addition, in silico predictions supported the probable pathogenicity of this variant. In this study, for the first time, we report a novel variant in the RELN gene, c.7456A>G; p.(Ser2486Gly), which completely co-segregates with AS. This association suggests potential insights into the pathophysiological bases of AS and it could broaden horizons toward new therapeutic strategies. © 2020, The Author(s), under exclusive licence to European Society of Human Genetics.
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