A de novo TOP2B variant associated with global developmental delay and autism spectrum disorder

Abstract

Abstract Background 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. Methods 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. Results 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. Conclusion Our study supports the finding that TOP2B variants may cause NDDs.

Keywords

• autism spectrum disorder
• global developmental delay
• TOP2B
• whole‐exome sequencing