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
-
- Zebrafish/genetics
- Animals
- Drosophila melanogaster/genetics
- Carrier Proteins/genetics*
- Mice, Knockout
- Heterozygote
- Mice
- Blotting, Western
- Phenotype
- Epilepsies, Myoclonic/genetics
- Drosophila Proteins/genetics*
- Immunoenzyme Techniques
- Calcium/metabolism
- Reverse Transcriptase Polymerase Chain Reaction
- DNA-Binding Proteins/genetics*
- Mutation/genetics*
- Nerve Tissue Proteins/genetics*
- Male
- In Situ Hybridization
- Female
- Zebrafish Proteins/genetics*
- Brain/metabolism
- Embryo, Nonmammalian/cytology
- Embryo, Nonmammalian/metabolism
- RNA, Messenger/genetics
- Tumor Suppressor Proteins/genetics*
- Adaptor Proteins, Signal Transducing
- Seizures/etiology*
- Seizures/metabolism
- Humans
- LIM Domain Proteins
- PubMed
- 21276947 Full text @ Am. J. Hum. Genet.
Citation
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. (2011) Mutations in Prickle Orthologs Cause Seizures in Flies, Mice, and Humans. American journal of human genetics. 88(2):138-149.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping