Identification and Characterization of Bone-related Genetic Variants in Families
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|ClinicalTrials.gov Identifier: NCT02762318|
Recruitment Status : Terminated (Lack of funding)
First Posted : May 4, 2016
Last Update Posted : July 31, 2020
|Condition or disease||Intervention/treatment|
|Skeletal Dysplasia||Other: Samples With DNA|
To identify novel genetic variants causing skeletal dysplasia in Qatari populations and to additionally develop an understanding of how those variants influence skeletal biology at a molecular and cellular level.
Achieving this goal will be split into two aims:
- Aim 1: Perform a clinical characterization of a study group of patients with various forms of skeletal dysplasia seen in pediatric orthopedics clinic at Hamad Medical center, HMC. This will be followed by whole exome or genome sequencing and analysis to search for novel pathogenic variants responsible for the clinical presentation of these patients
- Aim 2: The genes and variants identified in Aim 1 will be characterized to determine their effects on osteoblast and chondrocyte differentiation and function.
All the subjects will be recruited from the pool of patients seen by the Pediatric Orthopedic Consultants at the Bone and Joint Institute. Subjects will be coming to the clinic for their standard care. They will be identified during that visit as candidates for the study. They will then be told about the study by their physicians. If a patient is interested in participation, the physician will introduce the CRC to him/her who will proceed with the consent process.
Consenting and the study procedures might be performed during that same visit if time allows, or in a new scheduled visit arranged at that time.
This research will also involve a pedigree creation. Secondary subjects (family members or relatives) will be told about the study by the research subject. The secondary subject will be able to read a copy of the consent form, think of his participation, and if interested they will be told to contact the Investigators. A suitable time will then be arranged, by an appropriate member of the research team, for the secondary subject to visit the clinic in order to proceed with the consent process and the study procedures.
|Study Type :||Observational|
|Actual Enrollment :||5 participants|
|Official Title:||Identification and Characterization of Bone-related Genetic Variants in Families|
|Study Start Date :||December 2015|
|Actual Primary Completion Date :||July 2020|
|Actual Study Completion Date :||July 2020|
- Other: Samples With DNA
After consenting, all subjects have to undergo the following procedures:
Up to 25 ml of blood will be withdrawn. If for any reason, the blood sample cannot be obtained, a swab will be applied to the inside of the cheek to obtain saliva.
A questionnaire will be used to collect information about individual A routine physical exam will be performed. The subject's medical record will be reviewed To well document some of the specific phenotypes and conditions, physicians might take photographs of the affected body area.
For secondary subjects (relatives or family members), normal examination and routine lab tests/ imagining will be done if needed as per the related standard care.
- Clinical assessement of a study group of patients with various forms of skeletal dysplasia, followed by identification of novel pathogenic variants using whole exome/genome sequencing. [ Time Frame: 2-3 years ]
Patients will be selected for the study and will undergo:
Phenotyping by a combination of clinical history taking and examination, determination of bone mass, laboratory studies, Full exome sequencing Lastly, the variants present in each exome will be determined, and these variants will be classified according to their likelihood of being pathogenic.
- Biochemical and cellular characterization of the putative causative genes. [ Time Frame: 1-2 year ]
Chondrocytes or osteoblasts will be used to measure the following:
Putative gene expression in the skeletal system, How they influence osteoblast and chondrocyte differentiation how they alter the activity of the key molecular pathways governing the activity of osteoblasts and chondrocytes,
Biospecimen Retention: Samples With DNA
Blood, Cheek swab (optional)
[If for any reason, the blood sample cannot be obtained, a swab will be applied to the inside of the cheek to obtain saliva]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02762318
|Hamad Medical Corporation|
|Principal Investigator:||Ronald Crystal, MD||Weill Medical College of Cornell University|