2. Academic Validation
  3. Mutations in prickle orthologs cause seizures in flies, mice, and humans

Mutations in prickle orthologs cause seizures in flies, mice, and humans

  • Am J Hum Genet. 2011 Feb 11;88(2):138-49. doi: 10.1016/j.ajhg.2010.12.012.
Hirotaka Tao 1,  J Robert Manak,  Levi Sowers,  Xue Mei,  Hiroshi Kiyonari,  Takaya Abe,  Nader S Dahdaleh,  Tian Yang,  Shu Wu,  Shan Chen,  Mark H Fox,  Christina Gurnett,  Thomas Montine,  Thomas Bird,  Lisa G Shaffer,  Jill A Rosenfeld,  Juliann McConnell,  Suneeta Madan-Khetarpal,  Elizabeth Berry-Kravis,  Hilary Griesbach,  Russell P Saneto,  Matthew P Scott,  Dragana Antic,  Jordan Reed,  Riley Boland,  Salleh N Ehaideb,  Hatem El-Shanti,  Vinit B Mahajan,  Polly J Ferguson,  Jeffrey D Axelrod,  Anna-Elina Lehesjoki,  Bernd Fritzsch,  Diane C Slusarski,  John Wemmie,  Naoto Ueno,  Alexander G Bassuk
Affiliations

Affiliation

  • 1 Division of Morphogenesis, National Institute for Basic Biology, 38 Nishigonaka, Myodaiji, Okazaki, Japan.
PMID: 21276947 DOI: 10.1016/j.ajhg.2010.12.012
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.

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