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.
Subject(s)
Carrier Proteins/genetics , DNA-Binding Proteins/genetics , Drosophila Proteins/genetics , Mutation/genetics , Nerve Tissue Proteins/genetics , Seizures/etiology , Tumor Suppressor Proteins/genetics , Zebrafish Proteins/genetics , Adaptor Proteins, Signal Transducing , Animals , Blotting, Western , Brain/metabolism , Calcium/metabolism , 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 , Phenotype , RNA, Messenger/genetics , Reverse Transcriptase Polymerase Chain Reaction , Seizures/metabolism , Zebrafish/geneticsABSTRACT
This study aimed to analyze the perceptions of parents of children with clubfoot regarding the Ponseti method of treatment, and identify aspects of treatment that families found most difficult. Thirty families of children with clubfoot were treated with the Ponseti method over a 4-year period, and questionnaires were distributed at the conclusion of treatment. The most difficult components of treatment were identified. However, these challenges did not impact treatment outcome negatively. We hypothesize that a strong physician-patient relationship and high levels of parental education may decrease perceived difficulties of treatment with the Ponseti method.