Identification of de novo CSNK2A1 and CSNK2B variants in cases of global developmental delay with seizures.,Journal of Human Genetics

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Identification of de novo CSNK2A1 and CSNK2B variants in cases of global developmental delay with seizures.
Journal of Human Genetics ( IF 2.6 ) Pub Date : 2019-01-17 , DOI: 10.1038/s10038-018-0559-z
Mitsuko Nakashima _{1,

2} , Jun Tohyama ₃ , Eiji Nakagawa ₄ , Yoshihiro Watanabe ₅ , Ch'ng Gaik Siew ₆ , Chieng Siik Kwong ₇ , Kaori Yamoto ₈ , Takuya Hiraide ₈ , Tokiko Fukuda ₈ , Tadashi Kaname ₉ , Kazuhiko Nakabayashi ₁₀ , Kenichiro Hata ₁₀ , Tsutomu Ogata ₈ , Hirotomo Saitsu ₁ , Naomichi Matsumoto ₂

Affiliation

Department of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Department of Child Neurology, Nishi-Niigata Chuo National Hospital, Niigata, Japan.
Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan.
Department of Pediatrics, Yokohama City University Medical Center, Yokohama, Japan.
Department of Genetics, Kuala Lumpur Hospital, Kuala Lumpur, Malaysia.
Department of Pediatrics, Sarawak General Hospital, Sarawak, Malaysia.
Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Department of Genome Medicine, National Research Institute for Child Health and Development, Tokyo, Japan.
Department of Maternal-Fetal Biology, National Research Institute for Child Health and Development, Tokyo, Japan.

Casein kinase 2 (CK2) is a serine threonine kinase ubiquitously expressed in eukaryotic cells and involved in various cellular processes. In recent studies, de novo variants in CSNK2A1 and CSNK2B, which encode the subunits of CK2, have been identified in individuals with intellectual disability syndrome. In this study, we describe four patients with neurodevelopmental disorders possessing de novo variants in CSNK2A1 or CSNK2B. Using whole-exome sequencing, we detected two de novo variants in CSNK2A1 in two unrelated Japanese patients, a novel variant c.571C>T, p.(Arg191*) and a recurrent variant c.593A>G, p.(Lys198Arg), and two novel de novo variants in CSNK2B in Japanese and Malaysian patients, c.494A>G, p.(His165Arg) and c.533_534insGT, p.(Pro179Tyrfs*49), respectively. All four patients showed mild to profound intellectual disabilities, developmental delays, and various types of seizures. This and previous studies have found a total of 20 CSNK2A1 variants in 28 individuals with syndromic intellectual disability. The hotspot variant c.593A>G, p.(Lys198Arg) was found in eight of 28 patients. Meanwhile, only five CSNK2B variants were identified in five individuals with neurodevelopmental disorders. We reviewed the previous literature to verify the phenotypic spectrum of CSNK2A1- and CSNK2B-related syndromes.

中文翻译：

在癫痫发作导致全球发育延迟的情况下，从头鉴定CSNK2A1和CSNK2B变异。

酪蛋白激酶2（CK2）是在真核细胞中普遍表达并参与各种细胞过程的丝氨酸苏氨酸激酶。在最近的研究中，已经在患有智力障碍综合症的个体中发现了编码CK2亚基的CSNK2A1和CSNK2B的从头变异。在这项研究中，我们描述了4名在CSNK2A1或CSNK2B中具有从头变异的神经发育障碍患者。使用全外显子测序，我们在两名不相关的日本患者中检测到CSNK2A1中的两个从头变异，一个新变异c.571C> T，p。（Arg191 *）和一个复发变异c.593A> G，p。（Lys198Arg），以及日本和马来西亚患者CSNK2B中的两个新的从头突变，分别是c.494A> G，第p。（His165Arg）和c.533_534insGT，第p。（Pro179Tyrfs * 49）。所有四名患者均表现出轻度至重度智力障碍，发育迟缓和各种类型的癫痫发作。这项研究和以前的研究已经在28名患有智力障碍的个体中发现了总共20种CSNK2A1变体。在28位患者中的8位患者中发现了热点变异c.593A> G，p。（Lys198Arg）。同时，在五个具有神经发育障碍的个体中仅鉴定出五个CSNK2B变异体。我们回顾了以前的文献，以验证CSNK2A1和CSNK2B相关综合征的表型谱。

更新日期：2019-01-26

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