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

Sponsor

Beijing Tiantan Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT04485598

Collaborator

Beijing Municipal Science & Technology Commission (Other)

502

Enrollment

Location

Actual Duration (Months)

8.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Condition or Disease	Intervention/Treatment	Phase
Stroke, Acute Transient Ischemic Attack 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 Design

Study Type:

Observational

Actual Enrollment :

502 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Aug 21, 2015

Actual Primary Completion Date :

May 22, 2020

Actual Study Completion Date :

May 22, 2020

Outcome Measures

Primary Outcome Measures

Percentage of patients with certain etiologic diagnosis established with targeted sequencing [day 0]
Percentage of patients with certain etiologic diagnosis established with targeted sequencing

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.