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.

中文翻译：

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在一个患有强直性脊柱炎的伊朗家庭中鉴定RELN变体p。（Ser2486Gly）；RELN和AS的第一个关联。

强直性脊柱炎（AS）是一种常见的复杂性炎性疾病。然而，到目前为止，尚未报道该疾病具有单基因模式的独特基因。在本研究中，我们报告了一个伊朗大家庭，其中有几个受影响的AS成员。选择三个受影响的病例和两个健康的病例的DNA进行全外显子测序（WES）。经过几个过滤步骤后，检测到以下基因的候选变体：RELN，DNMT1，TAF4β，MUC16，DLG2和FAM208。然而，分离分析证实只有一种变体，即c.7456A> G的关联。该家族中具有AS的RELN基因中的p。（Ser2486Gly）。另外，计算机模拟预测支持该变体的可能致病性。在这项研究中，我们首次报道了RELN基因的一个新变异体，即c.7456A> G。第（Ser2486Gly），与AS完全隔离。这种关联表明对AS的病理生理基础有潜在的见解，并且可以为新的治疗策略开阔眼界。