Molecular Investigation of Human Hyperekplexia
Research type
Research Study
Full title
Genetic and biological basis of neuromotor disorder, hyperekplexia, and associated startle syndromes
IRAS ID
153885
Contact name
Owen Pickrell
Contact email
Sponsor organisation
University of Leicester, School of Psychology
Duration of Study in the UK
10 years, 0 months, 1 days
Research summary
Hyperekplexia is a rare neurological disorder characterized by an exaggerated startle response to sudden external stimuli and also increased muscle stiffness. Symptoms of hereditary hyperekplexia are usually present from birth and can also include hernia, feeding difficulties and life threatening breath holding spells. Hyperekeplexia is known to be caused by mutations in three genes that affect the brain glycinergic system. However, the known mutations do not account for all clinical cases of hyperekplexia. Further, little is understood about how mutations in these genes actually cause the disease.
This study aims to identify new genes that cause hyperekplexia and increase our understanding of it. To do this we will analyse DNA samples from patients with a clinical diagnosis of hyperekplexia to find new variants in the known genes and potentially in new genes as well. For patients where hyperekplexia appears later in life and is thought to be acquired, in collaboration with Oxford University, we will analyse their blood for evidence of glycinergic antibodies. To further our understanding of the biological mechanisms of hyperekplexia we will ask some patients with a confirmed mutation to undergo a magnetic resonance imaging (MRI) scan to look at the way in which the gene mutation has affected the brain structure or the way in which connections are made within the brain. We will also be asking some gene positive patients to give a small skin biopsy to generate pluripotent stem cells, which will allow us to study the effect of the gene mutation in neuronal cells to provide more detailed information the altered function of cells expressing the mutation.
Gaining more information about how hyperekplexia is caused will also help patients as we will be able to give them more information about their disorder and about how best to treat the symptoms.REC name
Wales REC 3
REC reference
15/WA/0150
Date of REC Opinion
18 May 2015
REC opinion
Unfavourable Opinion