Single gene disorders are typically individually rare but in aggregate account for a sizeable fraction of morbidity in the community. The era of large scale DNA sequencing has brought an unprecedented opportunity to define their cause and study their pathogenesis.
The Clinical Genetics Group study single gene disorders in children, with a particular emphasis in those that affect the development of the skeleton and the brain. These themes stem from a central interest in a group of disorders called the filaminopathies that are caused by mutations in a family of genes encoding proteins called filamins.
Somewhat unexpectedly, a disorder of brain development is also caused by mutation in one of the filamin genes. Our evolving interest has therefore led to a programme of research that studies the development of both of these organ systems.
Insights gained from these disorders have filled gaps in the understanding of how bone develops in response to chemical and mechanical forces and in parallel how stem cells in the brain are regulated to produce neurons that progress to build the human cerebral cortex.
Our close links with clinicians worldwide who submit samples to our research programme make clinical translation a key component of our work. Insights gained from our studies have the ability to define recurrence risk and prognosis for the families affected by these disorders.
Ongoing study of the mechanism by which these genetic defects lead to developmental disease will further inform the development of therapeutic strategies for more commonly arising disease states.