Dataset Information

Identification of RELN variant p.(Ser2486Gly) in an Iranian family with ankylosing spondylitis; the first association of RELN and AS.

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.

SUBMITTER: Garshasbi M

PROVIDER: S-EPMC7253431 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Identification of RELN variant p.(Ser2486Gly) in an Iranian family with ankylosing spondylitis; the first association of RELN and AS.

Garshasbi Masoud M Mahmoudi Mahdi M Razmara Ehsan E Vojdanian Mahdi M Aslani Saeed S Farhadi Elham E Jensen Lars Riff LR Arzaghi Seyed Masoud SM Poursani Shiva S Bitaraf Amirreza A Eidi Milad M Gharehdaghi Elika Esmaeilzadeh EE Kuss Andreas Walter AW Jamshidi Ahmadreza A

European journal of human genetics : EJHG 20200130 6

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. ...[more]

PMID: 32001840

Similar Datasets

Project description:BackgroundAnkylosing spondylitis (AS) is a chronic autoimmune disease affecting the sacroiliac joint. To date, few studies have examined the association between long non-coding RNAs (lncRNAs) and AS pathogenesis. As such, we herein sought to characterize patterns of AS-related lncRNA expression and to evaluate the potential role played by these lncRNAs in this complex autoimmune context.MethodsWe conducted a RNA-seq analysis of peripheral blood mononuclear cell (PBMC) samples isolated from five AS patients and corresponding controls. These data were then leveraged to characterize AS-related lncRNA expression patterns. We further conducted GO and KEGG enrichment analyses of the parental genes encoding these lncRNAs, and we confirmed the validity of our RNA-seq data by assessing the expression of six lncRNAs via qRT-PCR in 15 AS and control patient samples. Pearson correlation analyses were additionally employed to examine the associations between the expression levels of these six lncRNAs and patient clinical index values.ResultsWe detected 56,575 total lncRNAs in AS and control patient samples during our initial RNA-seq analysis, of which 200 and 70 were found to be up- and down-regulated (FC > 2 or < 0.05; P < 0.05), respectively, in AS samples relative to controls. In qRT-PCR validation assays, we confirmed the significant upregulation of NONHSAT118801.2, ENST00000444046, and NONHSAT183847.1 and the significant downregulation of NONHSAT205110.1, NONHSAT105444.2, and NONHSAT051856.2 in AS patient samples. We further found the expression of NONHSAT118801.2 and NONHSAT183847.1 to be positively correlated with disease severity.ConclusionOverall, our findings highlight several lncRNAs that are specifically expressed in PBMCs of AS patients, indicating that they may play key functions in the pathogenesis of this autoimmune disease. Specifically, we determined that NONHSAT118801.2 and NONHSAT183847.1 may influence the occurrence and development of AS.

Dataset Information

Identification of RELN variant p.(Ser2486Gly) in an Iranian family with ankylosing spondylitis; the first association of RELN and AS.

Publications

Identification of RELN variant p.(Ser2486Gly) in an Iranian family with ankylosing spondylitis; the first association of RELN and AS.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets