Identifying Novel Causes of Childhood Bone Fragility
Research type
Research Study
Full title
Identifying Novel Causes of Childhood Bone Fragility Through Whole Exome Sequencing
IRAS ID
186981
Contact name
Meena Balasubramanian
Contact email
Sponsor organisation
Sheffield Children's NHS Foundation Trust
Duration of Study in the UK
2 years, 0 months, 9 days
Research summary
Osteogenesis Imperfecta, also commonly referred to as Brittle Bone Disease is the most common form of inherited bone fragility. In Sheffield, we have the largest cohort of children with Osteogenesis Imperfecta (OI) within Western Europe. The Sheffield Diagnostic Genetics Service hosts genetic testing for OI within the UK and receives referrals for genetic analyses from all over the country. Currently, genetic testing is performed through targeted “Next Generation” sequencing but this is confined to the genes already published in the literature on OI.
Next generation sequencing: the new technology now available to us means that the genetic origins of many diseases are becoming clearer, and this is impacting on the development of new treatments. For example, the study of a rare childhood bone disease (Osteoporosis-Pseudoglioma syndrome) underpinned the development of two new osteoporosis treatments (Denosumab and Anti-sclerostin antibodies). We would like to use the same principles: i.e. next generation sequencing technology through whole exome sequencing (sequencing all the human genes) in a group of children with OI who are negative through current genetic testing and establish the genetic cause of their bone disease.
In the short term, improved understanding of genetic origins of bone disease will enable better provision of information to patients on their condition and inheritance pattern; in the long term, this offers the opportunity to identify pathways and targets specific to OI, and the hope of targeted treatments.
Although treatment for OI has substantially improved over the last decade, we need to do better. Treatment for OI currently only increases the quantity of the same defective bone but does not alter the quality of bone produced. We need to develop new and more effective treatments. To do this, first, we need to understand better the genetic origins of the disease, and how this affects bone formation.
REC name
Yorkshire & The Humber - South Yorkshire Research Ethics Committee
REC reference
15/YH/0362
Date of REC Opinion
5 Oct 2015
REC opinion
Further Information Favourable Opinion