Suggestive linkage of familial mesial temporal lobe epilepsy to chromosome 3q26

Manuela Fanciulli, Carlo Di Bonaventura, Gabriella Egeo, Jinane Fattouch, Emanuela Dazzo, Slobodanka Radovic, Alessandro Spadotto, Anna Teresa Giallonardo, Carlo Nobile

Research output: Contribution to journalArticle

Abstract

Purpose: To describe the clinical findings in a family with a benign form of mesial temporal lobe epilepsy and to identify the causative genetic factors. Methods: All participants were personally interviewed and underwent neurologic examination. The affected subjects underwent EEG and most of them neuroradiological examinations (MRI). All family members were genotyped with the HumanCytoSNP-12 v1.0 beadchip and linkage analysis was performed with Merlin and Simwalk2 programs. Exome sequencing was performed on HiSeq2000, after exome capture with SureSelect 50. Mb kit v2.0. Results: The family had 6 members with temporal lobe epilepsy. Age at seizure onset ranged from 8 to 13 years. Five patients had epigastric auras often associated to oro-alimentary automatic activity, 3 patients presented loss of contact, and 2 experienced secondary generalizations. Febrile seizures occurred in 2 family members, 1 of whom also had temporal lobe epilepsy. EEG showed focal slow waves and epileptic abnormalities on temporal regions in 1 patient and was normal in the other affected individuals. MRI was normal in all temporal lobe epilepsy patients. We performed single nucleotide polymorphism-array linkage analysis of the family and found suggestive evidence of linkage (LOD score=2.106) to a region on chromosome 3q26. Haplotype reconstruction supported the linkage data and showed that the majority of unaffected family members carried the haplotype at risk. Whole exome sequencing failed to identify pathogenic mutations in genes of the candidate region. Conclusions: Our data suggest the existence of a novel locus for benign familial mesial temporal lobe epilepsy on chromosome 3q26. Our failure to identify pathogenic mutations in genes of this region may be due to limitations of the exome sequencing technology.

Original languageEnglish
Pages (from-to)232-240
Number of pages9
JournalEpilepsy Research
Volume108
Issue number2
DOIs
Publication statusPublished - Feb 2014

Keywords

  • Exome sequencing
  • Linkage analysis
  • Neurogenetics
  • Temporal lobe epilepsy

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

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  • Cite this

    Fanciulli, M., Di Bonaventura, C., Egeo, G., Fattouch, J., Dazzo, E., Radovic, S., Spadotto, A., Giallonardo, A. T., & Nobile, C. (2014). Suggestive linkage of familial mesial temporal lobe epilepsy to chromosome 3q26. Epilepsy Research, 108(2), 232-240. https://doi.org/10.1016/j.eplepsyres.2013.11.002