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Background <p>Ataxia with oculomotor apraxia type 2 (AOA2), a rare autosomal recessive neurodegenerative disorder, exhibits marked clinical heterogeneity, thereby presenting substantial diagnostic challenges. This study conducts an investigation of two pedigrees with SETX gene mutation-associated AOA2, coupled with a review of the clinical manifestations and genetic characteristics documented in previously reported study.</p> Methods <p>Clinical data were collected from probands and their respective family members. A systematic literature review of AOA2 cases was conducted utilizing the PubMed, Google Scholar, and Web of Science databases to analyze the clinical and genetic characteristics.</p> Results <p>Both pedigrees exhibited progressive gait instability, dysarthria, peripheral neuropathy, cerebellar atrophy, and elevated α-fetoprotein (AFP). Genetic testing identified a homozygous c.7034_7036delTAA mutation in Pedigree A and compound heterozygous mutations (c.6812A &gt; G and exon7–10 deletion) in Pedigree B. Literature review of 216 patients revealed median onset age of 15&#xa0;years old (interquartile range: 13–18), with 77.1% developing symptoms between 10 and 20&#xa0;years. Key clinical features included ataxia (100%), dysarthria (99.2%), cerebellar atrophy (99.4%), and elevated AFP (97.6%). Oculomotor apraxia was observed in 34.2% of cases. Disease progression to wheelchair dependence averaged 15.9 ± 8.6&#xa0;years, with no significant differences observed in gender or adult onset and juvenile onset.</p> Conclusions <p>We identified novel SETX mutations in patients with AOA2. Notably, oculomotor apraxia is not always a clinical manifestation of AOA2 at diagnosis. Mild elevation of AFP could serve as a valuable diagnostic indicator in people with hereditary ataxia. Disease progression to wheelchair dependence may not be correlated with gender and age of onset.</p>

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Ataxia with oculomotor apraxia type 2: two pedigree studies and a comprehensive review

  • 期刊论文

  • 发表日期：

    2025年9月30日

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  • Lang Yang,
  • Sushuang Yang,
  • Jianfei Liu,
  • Xiaoyang Lei,
  • Dian He

摘要

Background

Ataxia with oculomotor apraxia type 2 (AOA2), a rare autosomal recessive neurodegenerative disorder, exhibits marked clinical heterogeneity, thereby presenting substantial diagnostic challenges. This study conducts an investigation of two pedigrees with SETX gene mutation-associated AOA2, coupled with a review of the clinical manifestations and genetic characteristics documented in previously reported study.

Methods

Clinical data were collected from probands and their respective family members. A systematic literature review of AOA2 cases was conducted utilizing the PubMed, Google Scholar, and Web of Science databases to analyze the clinical and genetic characteristics.

Results

Both pedigrees exhibited progressive gait instability, dysarthria, peripheral neuropathy, cerebellar atrophy, and elevated α-fetoprotein (AFP). Genetic testing identified a homozygous c.7034_7036delTAA mutation in Pedigree A and compound heterozygous mutations (c.6812A > G and exon7–10 deletion) in Pedigree B. Literature review of 216 patients revealed median onset age of 15 years old (interquartile range: 13–18), with 77.1% developing symptoms between 10 and 20 years. Key clinical features included ataxia (100%), dysarthria (99.2%), cerebellar atrophy (99.4%), and elevated AFP (97.6%). Oculomotor apraxia was observed in 34.2% of cases. Disease progression to wheelchair dependence averaged 15.9 ± 8.6 years, with no significant differences observed in gender or adult onset and juvenile onset.

Conclusions

We identified novel SETX mutations in patients with AOA2. Notably, oculomotor apraxia is not always a clinical manifestation of AOA2 at diagnosis. Mild elevation of AFP could serve as a valuable diagnostic indicator in people with hereditary ataxia. Disease progression to wheelchair dependence may not be correlated with gender and age of onset.