Genetic Identification of Monogenic Disorders in Early-onset Stroke Using Targeted Next Generation Sequencing Panel

Study Overview
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Brief Summary
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The study was designed as a multicenter multiracial prospective observational study of acute ischemic stroke and TIA patients across china. The purpose of this study is to determine the monogenic disorders incidence of Chinese early-onset stroke patients. We plan to consecutively enroll more than 500 patients with early-onset stroke(in the 18- to 45-year age range) admitted in stroke units within 7 days after symptoms onset in participating centers. These early-onset stroke patients are referred for targeted sequencing using 'cerebrovascular disease panel'. By analyzing the sequencing results, we intend to identify monogenic causes causing early-onset stroke and develop clinical algorithms that might assist the clinician in deciding in which early-onset stroke patients testing for monogenic causes of stroke.

Detailed Description
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The study was designed as a multicenter multiracial prospective observational study of acute ischemic stroke and TIA patients across china. The purpose of this study is to determine the monogenic disorders incidence of Chinese early-onset stroke patients. We plan to consecutively enroll more than 500 patients with early-onset stroke(in the 18- to 45-year age range) admitted in stroke units within 7 days after symptoms onset in participating centers. Patients fulfilling all of the inclusion criteria and none of the exclusion criteria will be referred for targeted sequencing using 'cerebrovascular disease panel'. When one or multiple pathogenic or possible pathogenic exonic mutations are found, a Sanger Sequencing (SS) on somatic DNA from peripheral blood leukocyte of the index case and affected relatives will be performed for the screening of the same mutations. And the sporadic patient's mutations will be checked by SS in the unaffected family members. By analyzing the sequencing results, we intend to identify monogenic causes causing early-onset stroke and develop clinical algorithms that might assist the clinician in deciding in which early-onset stroke patients testing for monogenic causes of stroke.

Official Title
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Genetic Identification of Monogenic Disorders in Early-onset Stroke Using Targeted Next Generation Sequencing Panel

Conditions
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Stroke, Acute, Transient Ischemic Attack, Single-gene Disorders

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of informed consent. Female or male aged ≥ 18 years and ≤ 45 years. Acute ischemic stroke or Transient ischemic attack((Neurological deficit attributed to focal brain ischemia, with resolution of the deficit within 24 hours of symptom onset) patients that can be enrolled within 7 days of symptoms onset defined by thelast see normalprinciple. Exclusion Criteria: Asymptomatic brain infarction Neurological deficit due to causes other than ischemic stroke or TIA

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with certain etiologic diagnosis established with targeted sequencing | Percentage of patients with certain etiologic diagnosis established with targeted sequencing | day 0 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Obtained read depth according to number of pooled samples | Obtained read depth according to number of pooled samples | day 0 | 
| Percentage of patients with variant with unknown significance | Percentage of patients with variant with unknown significance, needing supplementary analyses to prove its involvement in early-onset stroke | day 0 | 
| Clinical phenotype for each gene for which a causal mutation is identified by targeted sequencing panel | Clinical phenotype for each gene for which a causal mutation is identified by targeted sequencing panel | day 0 | 
| Time of analysis of NGS raw data | Time of analysis of NGS raw data | 30 days | 
| Incidence of certain single-gene disorders in early-onset stroke patients | Incidence of certain single-gene disorders in early-onset stroke patients | day 0 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stroke, Transient Ischemic Attack, Targeted sequencing panel, Early-onset