Ballardin Demetra, Cruz-Gamero Jose M, Bienvenu Thierry, Rebholz Heike
INSERM U1266, Institute of Psychiatry and Neuroscience of Paris, Université de Paris, Paris, France.
GHU-Paris Psychiatrie et Neurosciences, Hôpital Sainte Anne, Paris, France.
Front Mol Biosci. 2022 May 26;9:850559. doi: 10.3389/fmolb.2022.850559. eCollection 2022.
In recent years, variants in the catalytic and regulatory subunits of the kinase CK2 have been found to underlie two different, yet symptomatically overlapping neurodevelopmental disorders, termed Okur-Chung neurodevelopmental syndrome (OCNDS) and Poirier-Bienvenu neurodevelopmental syndrome (POBINDS). Both conditions are predominantly caused by missense or nonsense mono-allelic variants. They are characterized by a generalized developmental delay, intellectual disability, behavioral problems (hyperactivity, repetitive movements and social interaction deficits), hypotonia, motricity and verbalization deficits. One of the main features of POBINDS is epilepsies, which are present with much lower prevalence in patients with OCNDS. While a role for CK2 in brain functioning and development is well acknowledged, these findings for the first time clearly link CK2 to defined brain disorders. Our review will bring together patient data for both syndromes, aiming to link symptoms with genotypes, and to rationalize the symptoms through known cellular functions of CK2 that have been identified in preclinical and biochemical contexts. We will also compare the symptomatology and elaborate the specificities that distinguish the two syndromes.
近年来，已发现激酶CK2的催化亚基和调节亚基中的变异是两种不同但症状重叠的神经发育障碍的基础，这两种障碍分别称为奥库尔 - 钟氏神经发育综合征（OCNDS）和波里尔 - 比安弗努神经发育综合征（POBINDS）。这两种病症主要由错义或无义单等位基因变异引起。它们的特征包括广泛性发育迟缓、智力残疾、行为问题（多动、重复动作和社交互动缺陷）、肌张力减退、运动能力和语言表达缺陷。POBINDS的主要特征之一是癫痫，而在OCNDS患者中癫痫的患病率要低得多。虽然CK2在大脑功能和发育中的作用已得到充分认可，但这些发现首次明确将CK2与特定的脑部疾病联系起来。我们的综述将汇集这两种综合征的患者数据，旨在将症状与基因型联系起来，并通过在临床前和生化背景中已确定的CK2的已知细胞功能来解释这些症状。我们还将比较症状学并阐述区分这两种综合征的特异性。
