PUBLICATION

Mutations in Prickle Orthologs Cause Seizures in Flies, Mice, and Humans

Authors
Tao, H., Manak, J.R., Sowers, L., Mei, X., Kiyonari, H., Abe, T., Dahdaleh, N.S., Yang, T., Wu, S., Chen, S., Fox, M.H., Gurnett, C., Montine, T., Bird, T., Shaffer, L.G., Rosenfeld, J.A., McConnell, J., Madan-Khetarpal, S., Berry-Kravis, E., Griesbach, H., Saneto, R.P., Scott, M.P., Antic, D., Reed, J., Boland, R., Ehaideb, S.N., El-Shanti, H., Mahajan, V.B., Ferguson, P.J., Axelrod, J.D., Lehesjoki, A.E., Fritzsch, B., Slusarski, D.C., Wemmie, J., Ueno, N., and Bassuk, A.G.
ID
ZDB-PUB-110207-7
Date
2011
Source
American journal of human genetics   88(2): 138-149 (Journal)
Registered Authors
Fritzsch, Bernd, Slusarski, Diane C., Ueno, Naoto
Keywords
none
MeSH Terms
  • Adaptor Proteins, Signal Transducing
  • Animals
  • Blotting, Western
  • Brain/metabolism
  • Calcium/metabolism
  • Carrier Proteins/genetics*
  • DNA-Binding Proteins/genetics*
  • Drosophila Proteins/genetics*
  • Drosophila melanogaster/genetics
  • Embryo, Nonmammalian/cytology
  • Embryo, Nonmammalian/metabolism
  • Epilepsies, Myoclonic/genetics
  • Female
  • Heterozygote
  • Humans
  • Immunoenzyme Techniques
  • In Situ Hybridization
  • LIM Domain Proteins
  • Male
  • Mice
  • Mice, Knockout
  • Mutation/genetics*
  • Nerve Tissue Proteins/genetics*
  • Phenotype
  • RNA, Messenger/genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Seizures/etiology*
  • Seizures/metabolism
  • Tumor Suppressor Proteins/genetics*
  • Zebrafish/genetics
  • Zebrafish Proteins/genetics*
PubMed
21276947 Full text @ Am. J. Hum. Genet.
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.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping