Hereditary Ataxia Research on Multi-Omics and Neuroclinical Insights in the Yangtze Delta
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 5,000
- 试验地点
- 2
- 主要终点
- SARA scores
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Other
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
结局指标
主要结局
SARA scores
时间窗: 10 years
Scale for the Assessment and Rating of Ataxia (SARA) is a widely used tool specifically developed to quantify the severity of ataxia. It assesses multiple domains of ataxia, including gait, stance, sitting, speech, finger chase, nose-finger test, fast alternating hand movements, and heel-shin slide. It is applicable to patients with various forms of ataxia and provides a standardized method for tracking disease progression. * Minimum value: 0 * Maximum value: 40 * Interpretation: Higher scores indicate more severe ataxia (worse outcome).
MMSE scores
时间窗: 10 years
Mini-Mental State Examination (MMSE) is a brief screening tool used to assess cognitive function, including orientation, registration, attention and calculation, recall, and language. It is widely employed to detect cognitive impairment and monitor changes in cognitive status over time in various neurological disorders. * Minimum value: 0 * Maximum value: 30 * Interpretation: Higher scores indicate better cognitive function (better outcome).
ICARS scores
时间窗: 10 years
As a comprehensive assessment tool, International Cooperative Ataxia Rating Scale (ICARS) evaluates four main components of ataxia: postural and gait disturbances, limb ataxia, dysarthria, and oculomotor disorders. It is commonly used in clinical research and practice to measure the overall severity of ataxia, allowing for comparisons across different studies and patient populations. * Minimum value: 0 * Maximum value: 100 * Interpretation: Higher scores indicate more severe ataxia (worse outcome).
SDFS scores
时间窗: 10 years
Spinocerebellar Degeneration Functional Score (SDFS) focuses on assessing the functional status of patients with spinocerebellar degeneration by evaluating their ability to perform daily activities related to mobility. It ranges from 0 to 7： * 0: no functional handicap; * 1: no functional handicap but signs at examination; * 2: mild, able to run, walking unlimited; * 3: moderate, unable to run, limited walking without help; * 4: severe, walking with one stick; * 5: walking with two sticks; * 6: unable to walk, requiring wheelchair; * 7: confined to the bed. * Interpretation: Higher scores indicate worse functional status (worse outcome).
MoCA scores
时间窗: 10 years
Montreal Cognitive Assessment (MoCA) is a more sensitive tool than MMSE for detecting mild cognitive impairment. It assesses multiple cognitive domains, including attention, concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. It is particularly useful in identifying early cognitive changes in neurodegenerative diseases. * Minimum value: 0 * Maximum value: 30 * Interpretation: Higher scores indicate better cognitive function (better outcome; typically, a score ≥26 is considered normal).
Disease-causative genes
时间窗: Until the patient's causative gene(s) is definitively identified.
The participants' causative genes harboring pathogenic variants are reported in accordance with the guidelines established by the HUGO Gene Nomenclature Committee (HGNC).
Genome-wide methylation profiles in peripheral blood leukocytes
时间窗: 10 years
Genome-wide methylation profiles of participants will be measured using whole genome bisulfite sequencing (WGBS). The analysis will quantify methylation levels across all CpG sites in the genome of peripheral blood leukocytes, with methylation level defined as the ratio of methylated cytosines to total cytosines (methylated + unmethylated) at each CpG site. Genome-wide methylation profiles will be reported as the respective or average methylation ratio across all profiled CpG sites, with data normalized according to the ENCODE Consortium guidelines for WGBS data.
Disease-associated pathogenic genomic variants
时间窗: Until the patient's causative variant(s) is definitively identified.
By utilizing human genomic DNA research techniques such as polymerase chain reaction, Sanger sequencing, next-generation sequencing, and long-read sequencing, the reasonable pathogenic variants (including tandem repeat expansions, conventional sequencing variants, and copy number variations, etc.) that cause the symptom spectrum in particpants are identified and reported, in accordance with the guidelines of the American College of Medical Genetics and Genomics (ACMG) and the Human Genome Variation Society (HGVS).
Serum neurofilament light chain levels
时间窗: 10 years
Serum neurofilament light chain levels in participants are measured using single-molecule array (Simoa) technology.
次要结局
未报告次要终点