Clinical Trial: Identification and Characterization of Bone-related Genetic Variants in Families

Study Status: Enrolling by invitation
Recruit Status: Enrolling by invitation
Study Type: Observational

Official Title: Identification and Characterization of Bone-related Genetic Variants in Families

Brief Summary: 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.

Detailed Summary:

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 part
Sponsor: Weill Medical College of Cornell University

Current Primary Outcome: 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.


Original Primary Outcome: Same as current

Current Secondary Outcome: 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,



Original Secondary Outcome: Same as current

Information By: Weill Medical College of Cornell University

Dates:
Date Received: December 16, 2015
Date Started: December 2015
Date Completion: December 2020
Last Updated: May 15, 2017
Last Verified: May 2017