Genetic Risk Factors of the Sneddon Syndrome

NCT06850519 | Completed

• 1 other identifier: 1016/2021
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Sneddon syndrome (SS) is a rare disorder with an incidence of about 4/million/year that affects mainly young and predominantly female adults. It is characterized by recurrent strokes and livedo reticularis, a purple reticular patterning of the skin. A genetic predisposition to this disease, for which there is still no single therapy, is being discussed. Our group recently identified a homozygous nonsense mutation within epidermal growth factor repeat (EGFr) 19 of NOTCH3 in two siblings of a consanguineous family with Sneddon syndrome and pediatric stroke. In an attempt to find other possible contributing genes in Sneddon syndrome patients with adult-onset stroke, we also searched for loss-of-function variants in genes downstream of NOTCH3. In doing so, we found 2 patients carrying heterozygous loss-of-function variants in the PALLD and ANGPTL4 genes. Our results suggest that a bi-allelic loss-of-function mutation in NOTCH3 is a cause of familial Sneddon syndrome with pediatric stroke and that impaired NOTCH3 signaling is an underlying disease mechanism in general. In addition, we have identified several other promising variants that are either located in genes associated with NOTCH3 signaling or play a role in vascular function and stroke. Based on these results, we now want to investigate whether these aforementioned variants are detectable in a larger number of patients and additionally analyze whether other genetic variants also play a role in disease pathogenesis. The goal of our project is to identify risk variants for Sneddon syndrome by whole exome sequencing and subsequent conventional sequencing.... The detection of a risk gene would be a helpful tool for the diagnosis of Sneddon syndrome and a possible basis for new therapeutic approaches.

Conditions

Sneddon Syndrome

Outcome Measures

Primary Outcomes (1)

• potential genetic risk factor for Sneddon Syndrome present

  occurence of genetic variants in genes associated with Sneddon Syndrome

  18 months

Study Arms (1)

Patients with Sneddon

Whole exome sequencing

Genetic: Exome Sequencing and Sanger Sequencing

Interventions

Exome Sequencing and Sanger Sequencing GENETIC

Exome Sequencing and Sanger Sequencing

Patients with Sneddon

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with Sneddon syndrome based on standard diagnosis criteria of Sneddon syndrome

You may qualify if:

• Subjects must be at least 18years old.
• Affected subjects must have been clinically diagnosed with Sneddon Syndrome. When analyzing families with Sneddon syndrome, healthy family members and participants with only symptoms of the skin will be included if consent is obtained.Frau Elli Greisenegger
• Unaffected subjects or subjects with symptoms restricted to the skin must have at least one family member with the clinical diagnosis Sneddon syndrome participating in the study.
• Subjects must be able to communicate well with the investigator, to understand the requirements of the study, as well as to understand and sign thewritten informed consent(= informed consent approved by thelocalethics committee).

Sponsors & Collaborators

• Karl Landsteiner University of Health Sciences: lead
• Medical University of Vienna: collaborator
• Unidade Local de Saúde de Coimbra, EPE: collaborator
• Instituto de Investigación Marqués de Valdecilla: collaborator
• Technical University of Munich: collaborator
• Alfried Krupp Krankenhaus: collaborator
• University Hospital Tuebingen: collaborator

Study Sites (1)

Karl Landsteiner University

Sankt Pölten, 3100, Austria

Location

Biospecimen

Retention: SAMPLES WITH DNA

EDTA blood

MeSH Terms

Conditions

Sneddon Syndrome

Interventions

Exome Sequencing

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Whole Genome Sequencing; Sequence Analysis, DNA; Sequence Analysis; Genetic Techniques; Investigative Techniques

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2021
• First Posted: February 27, 2025
• Study Start: May 12, 2021
• Primary Completion: November 8, 2024
• Study Completion: November 8, 2024
• Last Updated: February 27, 2025

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)