Hereditary Ataxia Research on Multi-Omics and Neuroclinical Insights in the Yangtze Delta

Hereditary Ataxia Research on Multi-Omics and Neuroclinical Insights in the Yangtze Delta

The goal of this observational study is to explore the clinical and genetic characteristics, multi-omics profiles, disease mechanisms, biomarkers, and potential therapeutic targets of hereditary ataxia (HA) in patients diagnosed with HA, primarily in the Yangtze River Delta region of China. The main questions it aims to answer are:

• What are the key pathogenic genetic variants, modifying factors and special inheritance patterns underlying HA?
• How do multi-omics profiles correlate with clinical phenotypes, disease progress and mechanism in HA patients?
• What are the implications of these findings for clinical practice?

Participants will:

• Undergo retrospective and prospective clinical data collection through long-term follow-up to observe disease onset, progression, and outcomes.
• Provide biological samples (e.g., blood, skin) to establish a biobank for multi-omics analyses.
• Be characterized using multidimensional omics technologies to identify disease-related molecular signatures, progression mechanisms, and potential regulatory targets.

This project aims to establish a representative and continuously expanding cohort of hereditary ataxia in the Yangtze River Delta region of China. By integrating both retrospective and prospective study designs, the investigators will implement a observational ambispective cohort approach to comprehensively capture the natural history of the disease - including its onset, progression, and clinical outcomes - through systematic data collection from historical records and long-term follow-up of enrolled cases. In parallel, a biobank will be established by collecting biospecimens such as blood and skin samples from participants, providing high-quality biological materials for future research. Utilizing multi-omics technologies, including genomics, transcriptomics, epigenomics, etc., the investigators will explore key pathogenic genetic variants, disease-modifying factors, mechanisms underlying disease progression, biomarkers, and potential therapeutic targets. Through this integrated approach, the project is expected to significantly advance basic and translational research on hereditary ataxia, ultimately contributing to the development of precision diagnosis and effective intervention strategies for these debilitating neurodegenerative disorders.

Inclusion Criteria:

• Presence of progressive ataxia as a primary or persistent clinical feature;
• Sufficient evidence to exclude acquired causes of ataxia (e.g., chronic intoxication, immune-mediated inflammation, acquired vitamin deficiency, acute injury, stroke, infection, or space-occupying disorders);
• For sporadic late-onset cases (≥30 years), disease duration must exceed 3 years, with no prominent progressive autonomic dysfunction or other features indicative of multiple system atrophy-cerebellar type (MSA-C);
• Ability and willingness of the participant or legal guardian to provide informed consent and complete the entire study process.

Exclusion Criteria:

• Patients whose causative genes identified through genetic testing and analysis do not fall within the defined spectrum of hereditary ataxias, based on consensus classifications from the MDS Task Force on Genetic Movement Disorders and the SRCA Working Group, along with current research advancements;
• Presence of concurrent cerebrovascular disease, brain tumors, or severe systemic illness;
• Refusal to sign informed consent or provide biological samples by the participant or legal representative;
• Inability or unwillingness to participate in follow-up assessments.