Molecular Genetics and Functional Genomics, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Rare and Complex Epilepsy Unit, Department of Neuroscience, Bambino Gesu' Children's Hospital, IRCCS, Rome, Italy.
Neurosci Biobehav Rev. 2023 Sep;152:105299. doi: 10.1016/j.neubiorev.2023.105299. Epub 2023 Jun 28.
'Dominant mutations in CAMK2B, encoding a subunit of the calcium/calmodulin-dependent protein kinase II (CAMK2), a serine/threonine kinase playing a key role in synaptic plasticity, learning and memory, underlie a recently characterized neurodevelopmental disorder (MRD54) characterized by delayed psychomotor development, mild to severe intellectual disability, hypotonia, and behavioral abnormalities. Targeted therapies to treat MRD54 are currently unavailable. In this review, we revise current knowledge on the molecular and cellular mechanisms underlying the altered neuronal function associated with defective CAMKIIβ function. We also summarize the identified genotype-phenotype correlations and discuss the disease models that have been generated to profile the altered neuronal phenotype and understand the pathophysiology of this disease.
CAMK2B 编码钙/钙调蛋白依赖性蛋白激酶 II（CAMK2）的亚基，CAMK2 是一种丝氨酸/苏氨酸激酶，在突触可塑性、学习和记忆中起关键作用。CAMK2B 中的显性突变是一种新描述的神经发育障碍（MRD54）的基础，其特征为精神运动发育迟缓、轻度至重度智力障碍、张力减退和行为异常。目前尚无针对 MRD54 的靶向治疗方法。在这篇综述中，我们修改了与 CAMKIIβ 功能缺陷相关的改变神经元功能的分子和细胞机制的现有知识。我们还总结了已确定的基因型-表型相关性，并讨论了已生成的疾病模型，以描述改变的神经元表型并了解该疾病的病理生理学。
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