Identification of RELN variant p.(Ser2486Gly) in an Iranian family with ankylosing spondylitis; the first association of RELN and AS
Identification of RELN variant p.(Ser2486Gly) in an Iranian family with ankylosing spondylitis; the first association of RELN and AS
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DOI：
10.1038/s41431-020-0573-4
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发表时间：
2020-01-30
影响因子：
5.2
通讯作者：
Jamshidi, Ahmadreza
中科院分区：
文献类型：
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作者：
Garshasbi, Masoud;Mahmoudi, Mahdi;Jamshidi, Ahmadreza
强直性脊柱炎（Ankylosing spondylitis，AS）是一种常见的复杂性炎症性疾病，但迄今为止，尚未发现与AS相关的单基因模式的基因。在本研究中，我们报告了一个大的伊朗家庭与几个受影响的成员与AS。选择三名受影响的患者和两名健康患者的DNA进行全外显子组测序（WES）。经过几个过滤步骤后，检测到以下基因中的候选变体：DNMN、DNMT 1、TAF 4 β、MUC 16、DLG 2和FAM 208。然而，分离分析证实了只有一个变异体，c.7456A>G; p。该家族中AS患者RELN基因中的Ser 2486 Gly。此外，计算机模拟预测支持该变体的可能致病性。在这项研究中，我们第一次报告了一个新的变异体，c.7456A>G; p.（Ser 2486 Gly），其与AS完全共分离。这种关联表明了对AS病理生理基础的潜在见解，它可以拓宽新的治疗策略的视野。
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, TAF4 beta, 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.