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

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.

Study Overview

• Status: Completed
• Conditions: Transient Ischemic Attack; Stroke, Acute; Single-gene Disorders

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 502

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100050
      • Beijing Tian Tan Hospital, Capital Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Acute ischemic stroke or Transient ischemic attack patients from participating centers over China that can be enrolled within 7 days of symptoms onset defined by the"last see normal"principle.Female or male aged ≥ 18 years and ≤ 45 years.

Description

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 the"last see normal"principle.

Exclusion Criteria:

• Asymptomatic brain infarction
• Neurological deficit due to causes other than ischemic stroke or TIA

Study Plan

How is the study designed?

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital
• Collaborators: Beijing Municipal Science & Technology Commission
• Investigators: Principal Investigator: Wei Li, M.D, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China

Study record dates

Study Major Dates

• Study Start (Actual): August 21, 2015
• Primary Completion (Actual): May 22, 2020
• Study Completion (Actual): May 22, 2020

Study Registration Dates

• First Submitted: July 21, 2020
• First Submitted That Met QC Criteria: July 21, 2020
• First Posted (Actual): July 24, 2020

Study Record Updates

• Last Update Posted (Actual): July 24, 2020
• Last Update Submitted That Met QC Criteria: July 21, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Stroke; Transient Ischemic Attack; Early-onset; Targeted sequencing panel
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Stroke; Ischemic Attack, Transient
• Other Study ID Numbers: CNSR3-ngs-eos