SYNGAP1 is a gene that encodes the cytosolic protein SYNGAP1 (SYNaptic GTPase Activating Protein), an essential component of the postsynaptic density at excitatory glutamatergic neurons. SYNGAP1 plays critical roles in synaptic development, structure, function, and plasticity. Mutations in SYNGAP1 result in a neurodevelopmental disorder termed Mental retardation‐type 5 (MRD5, OMIM #612621) with a phenotype consisting of intellectual disability, motor impairments, and epilepsy, attesting to the importance of this protein for normal brain development. Here we review the clinical and pathophysiological aspects of SYNGAP1 mutations with a focus on their effect on synaptogenesis, neural circuit function, and cellular plasticity. We conclude by comparing the molecular pathogenesis of SYNGAP1 mutations with those of another neurodevelopmental disorder that affects dendritic function and cellular plasticity, fragile X syndrome. Insights into the molecular similarities and differences underlying these disorders could lead to rationale therapy development.

中文翻译：

---

Syngap1 突变：临床、遗传和病理生理特征

SYNGAP1 是一种编码胞质蛋白 SYNGAP1（SYNaptic GTPase Activating Protein）的基因，它是兴奋性谷氨酸能神经元突触后密度的重要组成部分。SYNGAP1 在突触发育、结构、功能和可塑性中起着关键作用。SYNGAP1 突变导致神经发育障碍，称为 5 型智力迟钝（MRD5，OMIM #612621），其表型包括智力障碍、运动障碍和癫痫，证明了这种蛋白质对正常大脑发育的重要性。在这里，我们回顾了 SYNGAP1 突变的临床和病理生理学方面，重点是它们对突触发生、神经回路功能和细胞可塑性的影响。我们通过比较 SYNGAP1 突变的分子发病机制与另一种影响树突功能和细胞可塑性的神经发育障碍（脆性 X 综合征）的分子发病机制得出结论。深入了解这些疾病背后的分子相似性和差异性可能会导致合理的治疗发展。