David A. Dyment

Investigator, CHEO Research Institute

Dr. David Dyment is a clinical investigator at the CHEO Research Institute and Associate Professor at the University of Ottawa. He completed his graduate training in the genetics of complex disease at the University of Oxford and later medical training at the University of Calgary. His clinical interest is neurogenetics with a focus on epilepsy and he works as a clinician in the Neurogenetics program at CHEO.

His current research interests include the identification of genes for human malformation syndromes and also novel genes associated with forms of epilepsy.  In addition, he has an active interest in model systems for Dravet syndrome and Spinal Muscular Atrophy and Progressive Myoclonic Epilepsy.  He is the recipient of a CIHR Clinical Investigator award and has a University of Ottawa Tier 2 Research Chair in Epilepsy Genetics.

Related News

Research Projects

  1. First reports of primary ciliary dyskinesia caused by a shared DNAH11 allele in Canadian Inuit


    The discovery of this homozygous DNAH11 variant in widely disparate parts of the Nunangat (Inuit homelands) suggests this is a founder mutation that may be widespread in Inuit. Thus, PCD may be an important cause of chronic lung, sinus, and middle ear disease in this population. Inuit with chronic lung disease, including bronchiectasis or laterality defects, should undergo genetic testing for PCD. Consideration of including PCD genetic analysis in routine newborn screening should be considered in Inuit regions.

  2. Outcome of over 1500 matches through the Matchmaker Exchange for rare disease gene discovery: The 2-year experience of Care4Rare Canada


    Matchmaking through the MME is an effective way to investigate novel candidate genes; however, it is a labor-intensive process. Engagement from the community to contribute phenotypic, genotypic, and inheritance data will ensure that matchmaking continues to be a useful approach in the future.

  3. PLPHP deficiency: clinical, genetic, biochemical, and mechanistic insights


    The vitamin B6-responsive disorders (B6RDs) are a clinically and genetically heterogeneous group of rare, autosomal recessive conditions (Clayton, 2006) with the hallmark feature of seizures uniquely responsive to treatment by the B6 vitamers pyridoxine and/or pyridoxal-5′-phosphate (PLP) (Baumgartner-Sigl et al., 2007; Basura et al., 2009). PLP is a cofactor for over 160 distinct catalytic functions (Percudani and Peracchi, 2009), including enzymes involved in glucose, lipid and amino acid metabolism (John, 1995; Percudani and Peracchi, 2003; Eliot and Kirsch, 2004), and for the synthesis of neurotransmitters, making it an essential vitamer for normal brain function (Surtees et al., 2006).

  4. Epilepsy genetics: Current knowledge, applications, and future directions


    Drug screening with in vitro and in vivo models of epilepsy can potentially facilitate new treatment strategies.

  5. Pyridoxine-dependent epilepsy in zebrafish caused by Aldh7a1 deficiency


    PYROXIDINE-DEPENDENT epilepsy (PDE, MIM #266100) is a rare autosomal recessively inherited metabolic disease (Gospe 2017) in which intractable and recurrent neonatal or infantile seizures are alleviated uniquely by high doses of pyridoxine (Pyr, vitamin B6) or pyridoxal 5′-phosphate (PLP) (Baxter 2001; Mills et al. 2006; Stockler et al. 2011). When untreated, PDE can lead to death, usually of status epilepticus (Gospe 2017). This condition is caused by mutations in the lysine degradation gene ALDH7A1 (Mills et al. 2006) that encodes α-aminoadipic-semialdehyde-dehydrogenase, which is also known as “Antiquitin” (Lee et al. 1994) due to its remarkable level of conservation through evolution (Supplemental Material, Figure S1). Loss of ALDH7A1 enzyme function leads to the pathogenic accumulation of the lysine intermediates aminoadipate semialdehyde (AASA) and its cyclic equilibrium form piperideine 6-carboxylate (P6C) in tissues including the central nervous system (CNS) [4] (Figure 1). P6C has been shown to react with and inactivate PLP (the active form of vitamin B6), a cofactor for over 140 enzymes including those involved in neurotransmission (Percudani and Peracchi 2003). It is thus hypothesized that the local or global depletion of PLP results in the Pyr-dependent seizures (Clayton 2006), possibly via disturbance of the PLP-dependent biosynthesis of γ-aminobutyric acid (GABA), the main cerebral inhibitory neurotransmitter. So far, clinical data from cerebrospinal fluid (CSF) measurements of these compounds were inconclusive and the pathophysiology of PDE remains to be fully elucidated.