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A Chinese Family with Digenic TBP/STUB1 Spinocerebellar Ataxia

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A Correction to this article was published on 24 February 2024

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Abstract

Spinocerebellar ataxias (SCAs) are inherited neurodegenerative diseases characterized by loss of balance, coordination, and slurred speech. Recently, a digenic mode of inheritance of TBP/STUB1 contributing to SCA was demonstrated. The clinical manifestations of SCATBP/STUB1 include not only ataxia but also obvious cognitive and behavioral impairment. Here, we describe a Chinese family with SCATBP/STUB1 and performed a literature search for similar cases. We identified a Chinese family with SCATBP/STUB1 and compare our clinical findings with other cases described in the literature so far. Four individuals in this family have been found to carry SCATBP/STUB1, of which three have clinical manifestations. A heterozygous deletion mutation in the STIP1-homologous and U-box containing protein 1 (STUB1) gene, NM_005861.4:c433_435del(p.K145del), was identified. The proband is a 34-year-old female with progressive dementia and dysarthria. The mother and uncle of the proband first presented with motor abnormalities and gradually developed cognitive impairment. The proband and her uncle showed cerebellar atrophy on MRI. The proband’s brother carried digenic variants but was asymptomatic. SCATBP/STUB1 is a novel SCA subtype. The main clinical manifestations are motor, cognitive, and behavioral abnormalities. Brain MRI shows significant cerebellar atrophy and cortical thinning. The independent segregation of TBP and STUB1 alleles should be considered when evaluating patients with cognitive impairment and ataxia.

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Data Availability

The original data presented in this study have been included in this article. Further inquiries can be directed to the corresponding authors.

Change history

Abbreviations

CCAS:

Cerebellar cognitive affective syndrome

CHIP:

HSP70-interacting protein

HSP:

Heat shock protein

MMSE:

Mini-Mental State Examination

MoCA:

Montreal Cognitive Assessment

MRI:

Magnetic resonance imaging

poly-Q:

Polyglutamine

SARA:

Scale for the Assessment and Rating of Ataxia

SCA:

Spinocerebellar ataxia

STUB1 :

STIP1-homologous and U-box containing protein 1

TBP :

TATA-box binding protein

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Acknowledgements

The authors thank the Infinite Med Co., Ltd. for performing genetic testing and gene structure analysis in our patients.

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Author notes

  1. Lili Liu and Juanjuan Chen contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, Peking University Shenzhen Hospital, Shenzhen, China

    Lili Liu, Juanjuan Chen, Guogao Zhang, Zhijian Lin, Di Chen & Jun Hu

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  1. Lili Liu
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  2. Juanjuan Chen
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  3. Guogao Zhang
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  4. Zhijian Lin
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  5. Di Chen
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  6. Jun Hu
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Contributions

LL and JC wrote the manuscript, performed literature retrieval and utilization, contributed to figure and table preparation, and helped with the diagnostic process. JH is the corresponding author of this study. JC, JH, ZL, GZ and DC were involved in patient care. JC assisted with the diagnostic process, supported the interpretation, and critically revised the manuscript. All authors contributed to the manuscript and approved the submitted version.

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Correspondence to Jun Hu.

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Ethics Statement

This study was reviewed and approved by the Medical Ethics Committee of Peking University, Shenzhen Hospital.

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Liu, L., Chen, J., Zhang, G. et al. A Chinese Family with Digenic TBP/STUB1 Spinocerebellar Ataxia. Cerebellum (2024). https://doi.org/10.1007/s12311-024-01664-3

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