Scholarlink

Background <p><i>ATP7B</i> is the gene that codes copper-transporting ATPase 2, whose homozygous variant causes Wilson disease, typically presenting with hepatic dysfunction and neurological manifestations. Although monoallelic <i>ATP7B</i> variant carriers are considered largely asymptomatic, recent observations suggest they may exhibit atypical movement disorders, including cerebellar ataxia.</p> Objective <p>To investigate the prevalence of monoallelic <i>ATP7B</i> variants in patients with various movement disorders including ataxia and to characterize associated clinical and neuroimaging findings.</p> Methods <p>This single-center hypothesis-generating retrospective study included 288 patients who underwent next-generation sequencing (NGS) panels for parkinsonism, dystonia, or ataxia. We calculated the prevalence of monoallelic <i>ATP7B</i> variants in each subgroup and compared these frequencies with the known carrier rate (1.14%–2.27%) in the Korean population. Clinical data and MRI findings of ataxic patients with monoallelic <i>ATP7B</i> variants were retrospectively reviewed.</p> Results <p>Of the 288 patients, 10 (3.47%) harbored monoallelic <i>ATP7B</i> variant. A significantly elevated prevalence 11.63% (5 patients out of 43) was observed in the ataxia subgroup, whereas carrier rates in parkinsonism (1.12%) and dystonia (4.55%) were not significantly higher than the assumed general population frequency of 1/44 (2.27%). Patients with ataxia and monoallelic <i>ATP7B</i> variants presented predominantly with adult-onset cerebellar dysarthria and gait ataxia. MRI revealed cerebellar atrophy among all five patients, with two patients additionally demonstrating increased diffusivity of putamen and severe pontine atrophy resembling multiple system atrophy.</p> Conclusion <p>Monoallelic <i>ATP7B</i> variants may appear enriched in patients with adult-onset cerebellar ataxia, suggesting that such genotype may be associated with cerebellar degeneration. Further large-scale, longitudinal, and mechanistic studies are required to validate such associations.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Monoallelic ATP7B variants in adult-onset cerebellar ataxia

  • 期刊论文

  • 发表日期：

    2026年3月21日

查看全文
  • Yoon Seob Kim,
  • Don Gueu Park,
  • Joo-Yeon Lee,
  • Jung Han Yoon

摘要

Background

ATP7B is the gene that codes copper-transporting ATPase 2, whose homozygous variant causes Wilson disease, typically presenting with hepatic dysfunction and neurological manifestations. Although monoallelic ATP7B variant carriers are considered largely asymptomatic, recent observations suggest they may exhibit atypical movement disorders, including cerebellar ataxia.

Objective

To investigate the prevalence of monoallelic ATP7B variants in patients with various movement disorders including ataxia and to characterize associated clinical and neuroimaging findings.

Methods

This single-center hypothesis-generating retrospective study included 288 patients who underwent next-generation sequencing (NGS) panels for parkinsonism, dystonia, or ataxia. We calculated the prevalence of monoallelic ATP7B variants in each subgroup and compared these frequencies with the known carrier rate (1.14%–2.27%) in the Korean population. Clinical data and MRI findings of ataxic patients with monoallelic ATP7B variants were retrospectively reviewed.

Results

Of the 288 patients, 10 (3.47%) harbored monoallelic ATP7B variant. A significantly elevated prevalence 11.63% (5 patients out of 43) was observed in the ataxia subgroup, whereas carrier rates in parkinsonism (1.12%) and dystonia (4.55%) were not significantly higher than the assumed general population frequency of 1/44 (2.27%). Patients with ataxia and monoallelic ATP7B variants presented predominantly with adult-onset cerebellar dysarthria and gait ataxia. MRI revealed cerebellar atrophy among all five patients, with two patients additionally demonstrating increased diffusivity of putamen and severe pontine atrophy resembling multiple system atrophy.

Conclusion

Monoallelic ATP7B variants may appear enriched in patients with adult-onset cerebellar ataxia, suggesting that such genotype may be associated with cerebellar degeneration. Further large-scale, longitudinal, and mechanistic studies are required to validate such associations.