Identification and Characterization of Bone-related Genetic Variants in Families
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- 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.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Family Based
- 时间视角
- Prospective
入排标准
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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)
结局指标
主要结局
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.
时间窗: 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.
次要结局
- Biochemical and cellular characterization of the putative causative genes.(1-2 year)