Journal
AMERICAN JOURNAL OF HUMAN GENETICS
Volume 88, Issue 2, Pages 138-149Publisher
CELL PRESS
DOI: 10.1016/j.ajhg.2010.12.012
Keywords
-
Categories
Funding
- National Institutes of Health [R01 NS064159, 3R01NS064159-02S1, R01 GM059823, RO1 CA112369, P50 AG05136, 1R21NS058309-01A1]
- VA
- Howard Hughes Medical Institute
Ask authors/readers for more resources
Epilepsy is heritable, yet few causative gene mutations have been identified, and thus far no human epilepsy gene mutations have been found to produce seizures in invertebrates. Here we show that mutations in prickle genes are associated with seizures in humans, mice, and flies. We identified human epilepsy patients with heterozygous mutations in either PRICKLE1 or PRICKLE2. In overexpression assays in zebrafish, prickle mutations resulted in aberrant prickle function. A seizure phenotype was present in the Prickle1-null mutant mouse, two Prickle1 point mutant (missense and nonsense) mice, and a Prickle2-null mutant mouse. Drosophila with prickle mutations displayed seizures that were responsive to anti-epileptic medication, and homozygous mutant embryos showed neuronal defects. These results suggest that prickle mutations have caused seizures throughout evolution.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available