Structural Chromosome Rearrangements and Brain Disorders

NCT06072079 | Enrolling By Invitation

• 1 other identifier: 2019-02078
• Study Type: observational
• Target: 10,000
• Locations: 1 country
• Sites: 1

Brief Summary

The project is focused on the detailed study of structural genomic variants (SVs). Such genetic mutations are in fact alterations in the DNA molecule structure and include copy number variants, inversions and translocations. A single event may affect many genes as well as regulatory regions and the specific phenotypic consequences will depend on the location, genetic content and type of SV. Many times, the specific disease-causing mechanism is not known. Here, the plan is to study the molecular genetic behavior of structural variants as well as the underlying mutational mechanisms involved. First, genome sequencing will be done to pinpoint the chromosomal breakpoints at the nucleotide level, characterize the genomic architecture at the breakpoints and study the relationship between structural variants and SNVs. Second, the aim is to study how structural variants impact gene expression. Finally, disease mechanisms will be functionally explored in vivo using zebrafish and in vitro using primary patient cells and induced pluripotent stem cells. The studies will focus on the origin, structure and impact of structural variation on human disease. The results will directly lead to a higher mutation detection rate in genetic diagnostics. Through a better understanding of disease mechanisms the findings will also assist in the development of novel biomarkers and therapeutic strategies for patients with rare genetic disorders.

Conditions

Rare Diseases; Genetic Disease; Chromosome Abnormality

Keywords

genome sequencing; structural variants

Outcome Measures

Primary Outcomes (1)

• Understanding disease mechanisms

  10 years

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Individuals that have undergone genetic investigations due to a suspected rare disease

You may qualify if:

• Individual with a suspected rare disease and/or chromosomal abnormality

You may not qualify if:

• No suspected rare disease or chromosome abnormalities

Sponsors & Collaborators

• Karolinska Institutet: lead
• Karolinska University Hospital: collaborator

Study Sites (1)

Anna Lindstrand

Stockholm, 19175, Sweden

Location

MeSH Terms

Conditions

Rare Diseases; Genetic Diseases, Inborn; Chromosome Aberrations

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD; Adjunct Professor

Study Record Dates

• First Submitted: October 2, 2023
• First Posted: October 10, 2023
• Study Start: December 20, 2019
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2029
• Last Updated: September 4, 2025

Record last verified: 2025-08

Locations

SE (1)