The state of the art in the genetic analysis of the epilepsies.
Genetic influences as causal factors in the epilepsies continue to be vigorously investigated, and we review several important studies of genes reported in 2006. To date, mutations in ion channel and neuroreceptor component genes have been reported in the small fraction of cases with clear Mendelian inheritance. These findings confirm that the so-called "channelopathies" are generally inherited as monogenic disorders. At the same time, the literature in common epilepsies abounds with reports of associations and reports of nonreplication of those association studies, primarily with channel genes. These contradictory reports can mostly be explained by confounding factors unique to genetic studies. The methodology of genetic studies and their common biases and confounding factors are also explained in this review. Amid the controversy, steady progress is being made on the epilepsies of complex inheritance, which represent the most common idiopathic epilepsy. Recent discoveries show that genes influencing the developmental assembly of neural circuits and neuronal metabolism may play a more prominent role in the common epilepsies than genes affecting membrane excitability and synaptic transmission.
Greenberg
David A
DA
Division of Statistical Genetics, Mailman School of Public Health, Columbia University Medical Center, 122 West 168th Street, 6th Floor, New York, NY 10032, USA. dag2005@columbia.edu
Pal
Deb K
DK
D015220:Calcium Channels / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000235:genetics; D004827:Epilepsy / Q000235:genetics*; D008040:Genetic Linkage; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D018079:Receptors, GABA / Q000145:classification / Q000235:genetics*; D014157:Transcription Factors; D018433:Twin Studies as Topic; D000092468:Bromodomain Containing Proteins
D015220:Calcium Channels; D002135:Calcium-Binding Proteins; D017346:Protein Serine-Threonine Kinases; D018079:Receptors, GABA; D014157:Transcription Factors; C098415:BRD2 protein, human; D000092468:Bromodomain Containing Proteins; C489648:EFHC1 protein, human