Decoding the Genetic Landscape of Skeletal Diseases
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- This is an observational study: the protocol does not assign a study treatment.
- Who it may be relevant to
- Registry conditions: Genetic Skeletal Diseases, Skeletal Dysplasia, Molecular Causes, Skeletal Disorder. Basic parameters: No limits · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Sweden
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
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.
Detailed 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.
Primary outcome measures
- New gene discoveries for genetic skeletal disorders (GSDs) [Time frame: 2023-2028]
- Improved knowledge regarding natural cause of rare GSDs [Time frame: 2023-2028]
Secondary outcome measures (2)
- Disease (GSD) associated traits and complications [Time frame: 2023-2028]
- Information on disease causing variants in GSD [Time frame: 2023-2028]
Eligibility criteria
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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: Yes
Study design
- Observational model
- Cohort
Study locations
Sweden · 1 center
- Karolinska University Hospital — Stockholm
Identifiers
NCT: NCT05876416 · 910715 · 2022-02647