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 M^{2, 3} ; Razmara E¹ ; Vojdanian M^{2, 3} ; Aslani S² ; Farhadi E^{2, 3} ; Jensen LR^{4, 5} ; Arzaghi SM⁶ ; Poursani S^{2, 3} ; Bitaraf A⁷ ; Eidi M¹ ; Gharehdaghi EE¹ ; Kuss AW⁴ ; Jamshidi A^{2, 3}
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.