Abstract
Heterozygous missense mutations in TUBB3 have been implicated in various neurological disorders encompassing either isolated congenital fibrosis of the extraocular muscles type 3 (CFEOM3) or complex cortical dysplasia with other brain malformations 1 (CDCBM1). The description of seizures in patients with TUBB3 mutations is rare. Here, we reported a patient who had febrile seizures before and focal seizure this time, which was diagnosed as epilepsy in combination with an abnormal EEG. MRI showed hypoplastic corpus callosum. Mutation analysis showed a novel de novo heterozygous variant of the TUBB3 gene (NM_006086), c.763G > A (p.V255I). The patient had global developmental delay, photophobia and elliptic pupils, but lacking extraocular muscle involvement and malformations of cortical development, which might be a less severe phenotype of TUBB3 mutations. This is the first report of elliptic pupils in a patient with TUBB3 mutations and expands the spectrum of TUBB3 phenotypes. It indicates that the phenotypic range of TUBB3 mutations might exist on more of a continuum than as a discrete entity, with severity ranging from mild to severe. Further studies are needed to elucidate the complete spectrum of TUBB3-related phenotypes.
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Acknowledgements
We thank the patient and his family for participating.
Funding
This work was supported by the Taishan Scholars Program of Shandong Province (no. tsqn201909191) and Youth Fund of the Affiliated Hospital of Qingdao University (no. QDFYQN2020014).
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Conception and design of the study: JX, ZS, YZ. Acquisition and analysis of data: SM, ZY, CY, FL, KL. Drafting a significant portion of the manuscript or figures: JX. All authors have read and approved the manuscript.
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The study was approved by the Ethics Committee of the Affiliated Hospital of Qingdao University. Written informed consent was obtained from the parents/guardians of the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the editor of this journal.
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Highlights
• We reported a patient carrying a novel de novo TUBB3 variant.
• The clinical presentations included global developmental delay, epilepsy, photophobia and elliptic pupils, and hypoplastic corpus callosum, without extraocular muscles involvement and malformations of cortical development (MCD).
• This is the first report of elliptic pupils in a patient with a TUBB3 variant, and expands the spectrum of TUBB3-related phenotypes.
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Xue, J., Song, Z., Ma, S. et al. A Novel De Novo TUBB3 Variant Causing Developmental Delay, Epilepsy and Mild Ophthalmological Symptoms in a Chinese Child. J Mol Neurosci 72, 37–44 (2022). https://doi.org/10.1007/s12031-021-01909-4
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DOI: https://doi.org/10.1007/s12031-021-01909-4