Abstract Details

Title Using Next-Generation Sequencing Technology To Identify Candidate Genes for Familial Mesial Temporal Lobe Epilepsy

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) S08 - (-)

Poster/Presentation
Number 001

Objective

Background Familial mesial temporal lobe epilepsy (FMTLE) is a clinically well characterized syndrome with an autosomal dominant inheritance. We have recently identified a candidate region for MTLE on chromosome (ch) 18p11.31.

Design/Methods We used DNA samples from three patients and one control, belonging to a single large family segregating FMTLE linked to ch 18p11.31. Samples were amplified by long range PCR and sequenced using the SOLiD System® (Applied Biosystems, USA). The innovation of this system consists of the paired analyzes and identification of each sequence pair, facilitating studies of complex genomes with a high degree of accuracy. Sequence data was aligned and analyzed by a logic algorithm developed in our laboratory using Perl language. Results from alignment were compared with databanks to verify possible functional relationship with the disease mechanism.

Results The candidate region sequenced had approximately 6 Mb and it contains 18 anoted genes (dbSNP). After initial bioinformatics analysis we identified 5019 single nucleotide polymorphisms (SNPs) in the sequenced region. Among them, 2474 SNPs were not present in the databases of polymorphisms previously described. After performing a series of pipeline adjustments we found three SNPs present only in the three patients and absent in the control. Furthermore, we found a small deletion also present in patients and absent in the control.

Conclusions Next-generation sequencing allowed a faster and reliable analysis of the candidate region previously identified by linkage studies in FMTLE. Using an interactive bioinformatics pipeline, we have identified putative functional variants in relevant candidate genes for FMTLE on ch 18p11.31. The candidate genes identified are involved in cortex development, development of neuronal projections, axons guidance and signal transduction, which are biological functions related to mechanisms potentially involved in FMTLE.

Authors/Disclosures
Renato O. Santos PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
Thomas C. Chelimsky, MD (Medical College of Wisconsin)	Dr. Chelimsky has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Proctor & Gamble. Dr. Chelimsky has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Various Legal Firms. Dr. Chelimsky has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Various Legal Firms. Dr. Chelimsky has received stock or an ownership interest from PainSTakers, LLC. The institution of Dr. Chelimsky has received research support from NIDDK. The institution of Dr. Chelimsky has received research support from Advancing a Healthier Wisconsin.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Clarissa L. Yasuda, MD, PhD (University of Campinas)	Prof. Yasuda has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for LIBBS. Prof. Yasuda has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ABBOTT. Prof. Yasuda has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for LIBBS.
Ana C. Coan, MD (Unicamp)	No disclosure on file
Marcia E. Morita-Sherman, MD (Eisai)	An immediate family member of Dr. Morita-Sherman has received personal compensation for serving as an employee of Forrester Research. Dr. Morita-Sherman has received personal compensation for serving as an employee of Eisai Inc.. An immediate family member of Dr. Morita-Sherman has stock in Forrester Research. The institution of Dr. Morita-Sherman has received research support from Cleveland Clinic.
Fernando Cendes, MD, PhD, FAAN (Departamento de Neurologia; FCM; UNICAMP)	Dr. Cendes has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB Pharma. Dr. Cendes has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for UCB Biopharma. Dr. Cendes has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for United Medical – Brazil. Dr. Cendes has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Zodiac Pharma . Dr. Cendes has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eurofarma – Brazil . Dr. Cendes has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Epilepsia. Dr. Cendes has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Frontiers in Neurology - Epilepsy. The institution of Dr. Cendes has received research support from São Paulo Research Foundation - FAPESP. The institution of Dr. Cendes has received research support from Conselho Nacional de Desenvolvimento Científico e Tecnológico - Brazil . The institution of Dr. Cendes has received research support from NIH.
Claudia V. Maurer-Morelli, PhD (University of Campinas)	No disclosure on file
Iscia Lopes-Cendes, MD, PhD (University of Campinas - UNICAMP)	No disclosure on file

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