Department of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Mol Genet Genomic Med. 2020 Mar;8(3):e1145. doi: 10.1002/mgg3.1145. Epub 2020 Jan 17.
TOP2B encodes type II topoisomerase beta, which controls topological changes during DNA transcription. TOP2B is expressed in the developing nervous system and is involved in brain development and neural differentiation. Recently, a de novo missense TOP2B variant (c.187C>T) has been identified in an individual with neurodevelopmental disorder (NDD). However, the association between TOP2B variants and NDDs remains uncertain.
Trio-based whole-exome sequencing was performed on a 7-year-old girl, presenting muscle hypotonia, stereotypic hand movements, epilepsy, global developmental delay, and autism spectrum disorder. Brain magnetic resonance images were normal. She was unable to walk independently and spoke no meaningful words.
We found a de novo variant in TOP2B (NM_001330700.1:c.187C>T, p.(His63Tyr)), which is identical to the previous case. The clinical features of the two individuals with the c.187C>T variant overlapped.
Our study supports the finding that TOP2B variants may cause NDDs.
TOP2B 编码 II 型拓扑异构酶β，它控制 DNA 转录过程中的拓扑变化。TOP2B 在发育中的神经系统中表达，参与脑发育和神经分化。最近，在一名神经发育障碍（NDD）患者中发现了一种新的 TOP2B 错义变体（c.187C>T）。然而，TOP2B 变体与 NDD 之间的关联仍不确定。
对一名 7 岁女孩进行了基于三核苷酸的全外显子组测序，该女孩表现为肌肉张力减退、刻板手运动、癫痫、全面发育迟缓伴自闭症谱系障碍。脑磁共振成像正常。她无法独立行走，也不会说有意义的话。
我们发现了 TOP2B 中的一个新的变体（NM_001330700.1:c.187C>T，p.（His63Tyr）），与之前的病例相同。两个携带 c.187C>T 变体的个体的临床特征重叠。
我们的研究支持 TOP2B 变体可能导致 NDD 的发现。
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