Decoding the Genetic Landscape of Skeletal Diseases

Skeletal Dysplasia Clinical Trial

— SKDLAND  

Official title:

Decoding the Genetic Landscape of Skeletal Diseases

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05876416
• Other study ID #: 910715
• Secondary ID: 2022-02647
• Status: Recruiting
• Start date: January 1, 2015
• Est. completion date: December 31, 2026

Study information

• Verified date: May 2023
• Source: Karolinska Institutet
• Contact: Giedre Grigelioniene, MD, PhD
• Phone: +46706287697
• Email: giedre.grigelioniene[@]ki.se
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Description:

Genetic skeletal disorders (GSDs) are a large group of rare diseases caused by abnormalities in genes regulating skeletal development. This 5-year project aims to (1) search for genetic causes for yet unsolved congenital skeletal disorders; (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. The project is a collaboration between the Dept of Clinical Genetics, Karolinska University Hospital, Lab of Clinical Genetics and Lab of Bone and Cartilage Physiology, Karolinska Institutet and Sahlgrenska Academy. In a well-characterized group of 300 GSD participants whose DNA samples were analyzed using whole genome sequencing (WGS), there are 120 study participants with unsolved diagnoses. For those participants, we search for molecular causes of GSDs using WGS and total 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. Our results improve diagnostics for GSDs, advance knowledge on pathogenesis and help establishing new individual follow-up and treatment strategies for patients with GSDs. This project increases understanding of skeletal pathophysiology and will contribute to the development of novel treatment methods for skeletal diseases.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 450
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

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

Exclusion Criteria:

No radiographic data available from clinical investigations

Suspected environmental or multifactorial causes

Related Conditions & MeSH terms

• Skeletal Disorder
• Skeletal Dysplasia

Locations

Country	Name	City	State
Sweden	Karolinska University Hospital	Stockholm

Sponsors (3)

Lead Sponsor	Collaborator
Karolinska Institutet	Göteborg University, Karolinska University Hospital

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Disease (GSD) associated traits and complications	The observations include internal malformations, metabolic, biochemical and growth parameters, and secondary complications.	2023-2028
Secondary	Information on disease causing variants in GSD	During the study we identify several novel disease causing variants in known GSD genes and report them to databases.	2023-2028