Jennifer Kearney
Last active: 5/27/2014

Profile

Within Mendelian disorders there can be considerable variability in the clinical phenotype among family members carrying the same mutation. This variable expressivity may be due to differences in inheritance of genetic modifier alleles. The role of genetic modifiers in influencing clinical severity has become increasingly important for understanding disease susceptibility and pathophysiology. Variable expressivity is a common feature in patients with inherited epilepsy caused by sodium channel mutations, since family members carrying the same mutation often exhibit differences in the clinical severity. We are studying genetic modifiers of epilepsy using mouse models with mutations in voltage-gated sodium channels. We use classical genetic approaches to identify modifier genes that contribute to phenotype variability in mouse models and also investigate whether the same genes contribute to epilepsy risk in patients. We then use neurophysiological approaches to study the mechanisms underlying phenotype modification. Isolation of susceptibility genes will contribute to understanding the molecular events of epileptogenesis and may suggest novel targets for the treatment of human epilepsy.

Publications

The following timeline graph is generated from all co-authored publications.

Featured publications are shown below:

  1. Strain- and age-dependent hippocampal neuron sodium currents correlate with epilepsy severity in Dravet syndrome mice. Mistry AM, Thompson CH, Miller AR, Vanoye CG, George AL, Kearney JA (2014) Neurobiol Dis : 1-11
    › Primary publication · 24434335 (PubMed) · PMC3968814 (PubMed Central)
  2. Novel SCN3A variants associated with focal epilepsy in children. Vanoye CG, Gurnett CA, Holland KD, George AL, Kearney JA (2014) Neurobiol Dis : 313-22
    › Primary publication · 24157691 (PubMed) · PMC3877720 (PubMed Central)
  3. Mapping genetic modifiers of survival in a mouse model of Dravet syndrome. Miller AR, Hawkins NA, McCollom CE, Kearney JA (2014) Genes Brain Behav 13(2): 163-72
    › Primary publication · 24152123 (PubMed) · PMC3930200 (PubMed Central)
  4. Advances in epilepsy genetics and genomics. Kearney JA (2012) Epilepsy Curr 12(4): 143-6
    › Primary publication · 22936886 (PubMed) · PMC3423212 (PubMed Central)
  5. Confirmation of an epilepsy modifier locus on mouse chromosome 11 and candidate gene analysis by RNA-Seq. Hawkins NA, Kearney JA (2012) Genes Brain Behav 11(4): 452-60
    › Primary publication · 22471526 (PubMed) · PMC3370141 (PubMed Central)
  6. Propranolol blocks cardiac and neuronal voltage-gated sodium channels. Wang DW, Mistry AM, Kahlig KM, Kearney JA, Xiang J, George AL (2010) Front Pharmacol : 144
    › Primary publication · 21833183 (PubMed) · PMC3153018 (PubMed Central)
  7. Voltage-gated potassium channel KCNV2 (Kv8.2) contributes to epilepsy susceptibility. Jorge BS, Campbell CM, Miller AR, Rutter ED, Gurnett CA, Vanoye CG, George AL, Kearney JA (2011) Proc Natl Acad Sci U S A 108(13): 5443-8
    › Primary publication · 21402906 (PubMed) · PMC3069171 (PubMed Central)
  8. Genetic modifiers of neurological disease. Kearney JA (2011) Curr Opin Genet Dev 21(3): 349-53
    › Primary publication · 21251811 (PubMed) · PMC3105121 (PubMed Central)
  9. Neuronal voltage-gated ion channels are genetic modifiers of generalized epilepsy with febrile seizures plus. Hawkins NA, Martin MS, Frankel WN, Kearney JA, Escayg A (2011) Neurobiol Dis 41(3): 655-60
    › Primary publication · 21156207 (PubMed) · PMC3035952 (PubMed Central)