Identification and Characterization of Bone-related Genetic Variants in Families

NCT02762318 | Terminated

• 1 other identifier: 14-00098
• Study Type: observational
• Target: 5
• Locations: 1 country
• Sites: 1

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.

Conditions

Skeletal Dysplasia

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  2-3 years

Secondary Outcomes (1)

• Biochemical and cellular characterization of the putative causative genes.

  1-2 year

Interventions

Samples With DNA OTHER

After consenting, all subjects have to undergo the following procedures: Up to 25 ml of blood will be withdrawn.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.

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

All our 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.

You may qualify if:

• All included individuals must provide informed consent
• Patients identified to have a skeletal dysplasia
• All ethnic backgrounds are acceptable
• Disease must be genetic with no evident environmental cause.
• Evidence of Mendelian Transmission determined by fulfilling one of the following criteria:
• Multiple affected family members (at least first-degree relative with disease)
• History of consanguinity
• Severe disease in newborn in the absence of family history
• Syndromic disease in single individuals
• Congenital abnormality affecting major organ system(s)
• Mendelianized extremes of common disease (e.g. bilateral developmental dysplasia of the hip)
• All ages will be included
• Rare diseases or rare forms of known diseases
• Unaffected family members or relatives of the individual with the primary syndrome

You may not qualify if:

• Individuals who do not consent will not be included
• Individuals for which a molecular diagnosis has already been established by alternative method (e.g. karyotype or known gene mutation)
• Diseases for which an environmental factor is most likely the cause (e.g. Traumatic bone injury or Rickets)
• Diseases of which late age of onset rule out Mendelian transmission
• Common Diseases for which late age of onset rule out Mendelian transmission (e.g.Osteoporosis)

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Hamad Medical Corporation: collaborator

Study Sites (1)

Hamad Medical Corporation

Doha, Qatar

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood, Cheek swab (optional) \[If for any reason, the blood sample cannot be obtained, a swab will be applied to the inside of the cheek to obtain saliva\]

MeSH Terms

Conditions

Mucopolysaccharidosis IV

Interventions

DNA

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

Intervention Hierarchy (Ancestors)

Nucleic Acids; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Ronald Crystal, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: FAMILY BASED
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2015
• First Posted: May 4, 2016
• Study Start: December 1, 2015
• Primary Completion: July 1, 2020
• Study Completion: July 1, 2020
• Last Updated: April 19, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will share

Locations

QA (1)