Decoding the Genetic Landscape of Skeletal Diseases

NCT05876416 | Recruiting

• 2 other identifiers: 9107152022-02647
• Study Type: observational
• Target: 450
• Locations: 1 country
• Sites: 1

Brief Summary

This 5-year project aims to (1) search for genetic causes for yet unsolved congenital skeletal disorders (GSDs); (2) study consequences of the newly identified pathogenic variants in cells and in transgenic mice, (3) summarize data on natural course and complications for different GSD groups. For patients with unsolved GSD, the investigators search for molecular causes of GSDs using whole genome sequencing (WGS) and total ribonucleic acid (RNA) sequencing. Candidate gene variants are selected using genome or transcriptome sequencing data, clinical findings and screening of omics databases. Causality of the new variants is studied in cells and in transgenic mice models. Molecular and clinical findings are summarized for different GSD groups.

Conditions

Genetic Skeletal Diseases; Skeletal Dysplasia; Molecular Causes; Skeletal Disorder

Outcome Measures

Primary Outcomes (2)

• New gene discoveries for genetic skeletal disorders (GSDs)

  2-3 new disease causes and disease entities identified and reported per year for GSDs.

  2023-2028

• Improved knowledge regarding natural cause of rare GSDs

  1-2 GSDs reported as small patient groups with the same condition and clinical characteristics/course.

  2023-2028

Secondary Outcomes (2)

• Disease (GSD) associated traits and complications

  2023-2028

• Information on disease causing variants in GSD

  2023-2028

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Individuals of any age with congenital skeletal diseases and their healthy relatives

You may qualify if:

• Clinically suspected skeletal dysplasia based on previous investigations
• Abnormal height
• Radiographic abnormalities of the skeleton in addition to other syndromic features
• Healthy relatives of the affected study participants

You may not qualify if:

• No radiographic data available from clinical investigations
• Suspected environmental or multifactorial causes

Sponsors & Collaborators

• Karolinska Institutet: lead
• Karolinska University Hospital: collaborator
• Göteborg University: collaborator

Study Sites (1)

Karolinska University Hospital

Stockholm, 17176, Sweden

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Genomic DNA samples, primary dermal fibroblasts, RNA from blood or fibroblasts

MeSH Terms

Conditions

Mucopolysaccharidosis IV

Condition Hierarchy (Ancestors)

Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Giedre Grigelioniene, MD,

  Dept Molecular Medicine and Surgery, KI

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Giedre Grigelioniene, MD, PhD

CONTACT

+46706287697; giedre.grigelioniene@ki.se

Hillevi Lindelöf, MD

CONTACT

Hillevi.Lindelof@ki.se

Study Design

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

Study Record Dates

• First Submitted: April 16, 2023
• First Posted: May 25, 2023
• Study Start: January 1, 2015
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 25, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)