LINKAGE STUDY OF VOLTAGE-GATED POTASSIUM CHANNELS IN FAMILIAL MESIAL TEMPORAL LOBE EPILEPSY: A PROGRESS REPORT
Abstract number :
2.196
Submission category :
Year :
2003
Submission ID :
1161
Source :
www.aesnet.org
Presentation date :
12/6/2003 12:00:00 AM
Published date :
Dec 1, 2003, 06:00 AM
Authors :
Claudia V. Maurer-Morelli, Neide F. Santos, Rodrigo Secolin, Rafael B. Marchesini, Eliane Kobayashi, Fernando Cendes, Iscia Lopes-Cendes Department of Medical Genetics, Campinas University State - UNICAMP, Campinas, Sao Paulo, Brazil; Department of Neurol
Voltage-gated potassium channels (VGKCs) play a critical role in the regulation of neuronal excitability. VGKCs have been implicated in some types of idiophatic and symptomatic epilepsies. Recently, a type of autoimmune limbic encephalitis (LE) was associated with antibodies against VGKCs. In addition, patients with LE showed increased T2 signal abnormalities in limbic structures. We recently described a large group of families segregating temporal lobe epilepsy (TLE) associated with ictal semiology of mesial temporal onset and MRI abnormalities in the mesial structures. Pedigrees analysis suggest an autosomal dominant inheritance. The objective of this study is to carry out linkage studies in familial mesial TLE in order to investigate whether VGKC gene mutations may be present in these families.
We studied 53 unrelated families segregating familial mesial TLE. Among these families we have identified two kindreds that are informative for linkage analysis: F-10 and F-26. A total of 57 individuals, including 32 patients were analyzed in this study. We searched on the Map Viewer database for all subunits of VGKCs, a total of 45 candidate genes were identified in different human chromosomes. We chose a total of 83 polymorphic dinucleotide repeat markers, which flank all the VGKCs genes identified. The screening was performed by PCR amplification. Two-point lod scores (Z) were calculated for each family separately using the MLINK program from the LINKAGE package. The region is considered excluded when Z [le] -2.
We have genotyped 47 markers, which excluded 21 VGKC candidate genes. The two Brazilian families segregating mesial TLE showed significant negative lod score for all markers genotyped, ranging from -2.43 to -7.66 at different recombination fractions.
Linkage studies are very efficient to identify disease related loci. By this method we can confirm or exclude genetic linkage between selected markers and disease loci. In the present study, we significantly excluded linkage between familial mesial TLE and about 47% of VGKCs genes mapped.
[Supported by: FAPESP.]