TBP Repeat Expansion Analysis in Patients Carrying Heterozygous STUB1 Variants.

IF 7.4 1区医学 Q1 CLINICAL NEUROLOGY Movement Disorders Pub Date : 2025-02-14 DOI:10.1002/mds.30147

Jonathan De Winter, Liedewei Van de Vondel, Kristof Van Schil, Tine Deconinck, Katrien Storm, Karine Geens, Charlotte Sommeling, David Crosiers, Emke Marechal, Willem De Ridder, Peter De Jonghe, Jonathan Baets

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引用次数: 0

Abstract

Background: The cooccurrence of intermediate (40-49 CAG/CAA) TBP repeat expansions with STUB1 variants questions the pathogenicity of monoallelic STUB1 variants in cerebellar ataxia.

Objective: The objective of this study was to describe the phenotypic spectrum of heterozygous STUB1 variants with or without intermediate TBP repeat expansions.

Methods: We determined the presence of TBP repeat expansions and STUB1 variants in six families with cerebellar ataxia.

Results: Cooccurrence of both genotypes in one family resulted in cerebellar ataxia, involving cognitive and extrapyramidal complications. Variable degrees of cerebellar ataxia and cognitive impairment were found in four families carrying a heterozygous STUB1 variant and normal TBP alleles. Finally, we report one patient with a mild late-onset cerebellar ataxia carrying an intermediate expanded TBP allele without the presence of a STUB1 variant.

Conclusions: Heterozygous STUB1 variants are associated with a milder phenotype and reduced penetrance compared with the cosegregation with intermediate TBP alleles, which causes a fully penetrant complicated form of cerebellar ataxia. © 2025 International Parkinson and Movement Disorder Society.

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来源期刊

Movement Disorders 医学-临床神经学

CiteScore

13.30

自引率

8.10%

发文量

371

审稿时长

12 months

期刊介绍： Movement Disorders publishes a variety of content types including Reviews, Viewpoints, Full Length Articles, Historical Reports, Brief Reports, and Letters. The journal considers original manuscripts on topics related to the diagnosis, therapeutics, pharmacology, biochemistry, physiology, etiology, genetics, and epidemiology of movement disorders. Appropriate topics include Parkinsonism, Chorea, Tremors, Dystonia, Myoclonus, Tics, Tardive Dyskinesia, Spasticity, and Ataxia.

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