Thrombocytopenia‐absent radius (TAR) syndrome is characterized by radial defect and neonatal thrombocytopenia. It is caused by biallelic variants of RBM8A gene (1q21.1) with the association of a null allele and a hypomorphic noncoding variant. RBM8A encodes Y14, a core protein of the exon junction complex involved in messenger RNA maturation. To date, only two hypomorphic variants have been identified. We report on a cohort of 26 patients affected with TAR syndrome and carrying biallelic variants in RBM8A . Half patients carried a 1q21.1 deletion and one of the two known hypomorphic variants. Four novel noncoding variants of RBM8A were identified in the remaining patients. We developed experimental models enabling their functional characterization in vitro. Two variants, located respectively in the 5′‐untranslated region (5′‐UTR) and 3′‐UTR regions, are responsible for a diminished expression whereas two intronic variants alter splicing. Our results bring new insights into the molecular knowledge of TAR syndrome and enabled us to propose genetic counseling for patients' families.

中文翻译：

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TAR 综合征：一组 26 名患者的临床和分子特征以及 RBM8A 新型非编码变体的描述。

血小板减少症-无桡骨（TAR）综合征的特点是桡骨缺损和新生儿血小板减少症。它是由RBM8A基因 (1q21.1)的双等位基因变异与无效等位基因和亚形非编码变异相关联引起的。RBM8A编码 Y14，这是参与信使 RNA 成熟的外显子连接复合物的核心蛋白。迄今为止，仅发现了两个亚形变体。我们报告了 26 名患有 TAR 综合征并在RBM8A 中携带双等位基因变异的患者队列。一半患者携带 1q21.1 缺失和两个已知的亚形变体之一。RBM8A 的四种新型非编码变体在其余患者中进行了鉴定。我们开发了实验模型，使其能够在体外进行功能表征。分别位于 5'-非翻译区 (5'-UTR) 和 3'-UTR 区域的两个变体导致表达减少，而两个内含子变体改变剪接。我们的研究结果为 TAR 综合征的分子知识带来了新的见解，并使我们能够为患者家属提供遗传咨询。