Journal article
Mutations in prickle orthologs cause seizures in flies, mice, and humans
American journal of human genetics, Vol.88(2), pp.138-149
02/11/2011
DOI: 10.1016/j.ajhg.2010.12.012
PMCID: PMC3035715
PMID: 21276947
Abstract
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.
Details
- Title: Subtitle
- Mutations in prickle orthologs cause seizures in flies, mice, and humans
- Creators
- Hirotaka Tao - Division of Morphogenesis, National Institute for Basic Biology, 38 Nishigonaka, Myodaiji, Okazaki, JapanJ Robert ManakLevi SowersXue MeiHiroshi KiyonariTakaya AbeNader S DahdalehTian Yang - University of IowaShu WuShan ChenJuliann McConnellSuneeta Madan-KhetarpalElizabeth Berry-KravisHilary GriesbachRussell P SanetoMatthew P ScottDragana AnticJordan ReedRiley BolandSalleh N EhaidebHatem El-ShantiVinit B MahajanPolly J FergusonJeffrey D AxelrodAnna-Elina LehesjokiMark H FoxBernd FritzschChristina GurnettDiane C SlusarskiThomas MontineJohn WemmieThomas BirdNaoto UenoAlexander G BassukLisa G ShafferJill A Rosenfeld
- Resource Type
- Journal article
- Publication Details
- American journal of human genetics, Vol.88(2), pp.138-149
- DOI
- 10.1016/j.ajhg.2010.12.012
- PMID
- 21276947
- PMCID
- PMC3035715
- NLM abbreviation
- Am J Hum Genet
- ISSN
- 1537-6605
- eISSN
- 1537-6605
- Publisher
- United States
- Grant note
- R21 NS058309 / NINDS NIH HHS 3R01NS064159-02S1 / NINDS NIH HHS UL1 RR025014 / NCRR NIH HHS R01 NS064159 / NINDS NIH HHS R01 GM059823 / NIGMS NIH HHS Howard Hughes Medical Institute P50 AG05136 / NIA NIH HHS 1R21NS058309-01A1 / NINDS NIH HHS P50 AG005136 / NIA NIH HHS R01 GM097081 / NIGMS NIH HHS R01 CA112369 / NCI NIH HHS
- Language
- English
- Date published
- 02/11/2011
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Psychiatry; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Biology; Craniofacial Anomalies Research Center; Rheumatology, Allergy, and Immunology; Neurology (Pediatrics); Neurosurgery; Internal Medicine
- Record Identifier
- 9983992098602771
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