Abstract Details

Title Next Generation Sequencing Reveals Candidate Genes for X-Linked Bilateral Congenital Perisylvian Polymicrogyria Syndrome

Topic Epilepsy

Presentation(s) P05 - (-)

Poster/Presentation
Number 089

Objective

Background BACKGROUND: BCPP is the most common form of polymicrogyria. Familial recurrence was described for BCPP and different patterns of inheritance have been identified. Recently, chromosome Xq28 has been identified as a candidate locus for BCPP. This is a highly repetitive region, making it prone to non-homologous recombination events that result in duplications and deletions of the genetic material. Recently, our group has identified a large family with an X-linked dominantly inherited BCPP.

Design/Methods DESIGN/METHODS: Four family members, three affected and one unaffected, were submitted to next generation sequencing. All exons of the X chromosome were captured with SureSelectXT technology (Agilent Technologies) and sequenced in a high-performance Hiseq sequencing equipment (Illumina). In addition, in order to assess whether a submicroscopic structural rearrangement is involved in BCPP, three patients were submitted to HD Cytoscan Array (Affymetrix).

Results RESULTS: All exons were captured and sequenced with 50x coverage. Approximately 3402 variants present in several genes were indentified. After performing a series of pipeline adjustments using a logic algorithm developed in our laboratory we found 22 candidate variants present in the 12 genes which were present in the patients but were absent in the control individual. HD Cytoscan Array analysis did not reveal structural X chromosome rearrangements in patients evaluated.

Conclusions CONCLUSIONS: Bioinformatics analysis of high performance sequencing data revealed two genes as potential candidates for BCPP etiology in the family studied. Putative roles related to development and/or cell division pathways make the two candidate genes identified relevant for BCPP. In addition, we conclude that gross chromosomal abnormalities are not involved with BCPP etiology in this family, thus point mutations or small deletions are likely to be the event leading to this syndrome.

Authors/Disclosures
PRESENTER	No disclosure on file
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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.
Marilisa M. Guerreiro, MD (State University of Campinas)	No disclosure on file
Iscia Lopes-Cendes, MD, PhD (University of Campinas - UNICAMP)	No disclosure on file
	No disclosure on file

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