Intellectual disability (ID) describes a wide range of serious human diseases caused by defects in central nervous system development and function. Some mutant genes have been found to be associated with these diseases, but not all cases can be explained, thus suggesting that other disease‐causing genes have not yet been discovered. Sialic acid is involved in a number of key biological processes, including embryo formation, nerve cell growth, and cancer cell metastasis, and very recently it has been suggested that N‐acetylneuraminic acid synthase‐mediated synthesis of sialic acid is required for brain and skeletal development. CMP‐sialic acid synthetase (CMAS) is one of four enzymes involved in NeuNAc metabolism, as it catalyzes the formation of CMP‐NeuNAc. Before the present study, no links between mutations in CMAS and incidences of human ID had been reported. In the current study, we recruited a recessive nonsyndromic ID pedigree with consanguineous marriage in which all patients have typical clinical manifestations of ID. We identified the NM_018686.3:c.563G > A (p.Arg188His) substitution in CMAS as being responsible for the disease in this family. Conservation analysis, structural prediction, and enzyme activity experiments demonstrated that (p.Arg188His) influences protein dimerization and alters CMAS enzyme activity. Our results offer a new orientation for future research and clinical diagnosis.

中文翻译：

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CMAS 纯合突变导致哈萨克家庭常染色体隐性智力障碍

智力障碍 (ID) 描述了由中枢神经系统发育和功能缺陷引起的一系列严重的人类疾病。已发现一些突变基因与这些疾病有关，但并非所有病例都能得到解释，从而表明尚未发现其他致病基因。唾液酸参与许多关键的生物过程，包括胚胎形成、神经细胞生长和癌细胞转移，最近有人提出，大脑和骨骼需要 N-乙酰神经氨酸合酶介导的唾液酸合成。发展。CMP-唾液酸合成酶 (CMAS) 是参与 NeuNAc 代谢的四种酶之一，因为它催化 CMP-NeuNAc 的形成。在本研究之前，没有报道 CMAS 突变与人类 ID 发生率之间存在联系。在目前的研究中，我们招募了一个具有近亲婚姻的隐性非综合征 ID 谱系，其中所有患者都具有 ID 的典型临床表现。我们确定 CMAS 中的 NM_018686.3:c.563G > A (p.Arg188His) 替代是导致该家族疾病的原因。保守性分析、结构预测和酶活性实验表明 (p.Arg188His) 影响蛋白质二聚化并改变 CMAS 酶活性。我们的结果为未来的研究和临床诊断提供了新的方向。CMAS 中的 (p.Arg188His) 替代是导致该家族疾病的原因。保守性分析、结构预测和酶活性实验表明 (p.Arg188His) 影响蛋白质二聚化并改变 CMAS 酶活性。我们的结果为未来的研究和临床诊断提供了新的方向。CMAS 中的 (p.Arg188His) 替代是导致该家族疾病的原因。保守性分析、结构预测和酶活性实验表明 (p.Arg188His) 影响蛋白质二聚化并改变 CMAS 酶活性。我们的结果为未来的研究和临床诊断提供了新的方向。