Genetic Risk Factors of the Sneddon Syndrome

NCT ID: NCT06850519

Last Updated: 2025-02-27

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 40 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-05-12
• Study Completion Date: 2024-11-08

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

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Study Groups

Patients with Sneddon

Whole exome sequencing

Exome Sequencing and Sanger Sequencing

Intervention Type: GENETIC

Exome Sequencing and Sanger Sequencing

Interventions

Exome Sequencing and Sanger Sequencing

Exome Sequencing and Sanger Sequencing

Intervention Type: GENETIC

Eligibility Criteria

Inclusion Criteria

• 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).

Exclusion Criteria

• Subjects who are unable to communicate well with the investigator, to understand the requirements of the study, as well as to understand and sign the written informed consent, are not eligible for inclusion in this study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Medical University of Vienna

OTHER

Sponsor Role: collaborator

Unidade Local de Saúde de Coimbra, EPE

OTHER

Sponsor Role: collaborator

Instituto de Investigación Marqués de Valdecilla

OTHER

Sponsor Role: collaborator

Technical University of Munich

OTHER

Sponsor Role: collaborator

Alfried Krupp Krankenhaus

OTHER

Sponsor Role: collaborator

University Hospital Tuebingen

OTHER

Sponsor Role: collaborator

Karl Landsteiner University of Health Sciences

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Karl Landsteiner University

Sankt Pölten, , Austria

Countries

Austria

Other Identifiers

1016/2021

Identifier Type: -

Identifier Source: org_study_id