Identity by descent fine mapping of familial adult myoclonus epilepsy (FAME) to 2p11.2–2q11.2

Lyndal Henden, Saskia Freytag, Zaid Afawi, S. Baldassari, Samuel F. Berkovic, Francesca Bisulli, Laura Canafoglia, Giorgio Nevio Casari, Douglas E. Crompton, Christel Depienne, Joseph Gecz, Renzo Guerrini, Ingo Helbig, E. Hirsch, Boris Keren, Karl Martin Klein, P. Labauge, Eric Leguern, Laura Licchetta, Davide MeiCaroline Nava, T. Pippucci, G. Rudolf, Ingrid E. Scheffer, Pasquale Striano, Paolo Tinuper, Federico Zara, Mark A. Corbett, Melanie Bahlo

Research output: Contribution to journalArticle

Abstract

Familial adult myoclonus epilepsy (FAME) is a rare autosomal dominant disorder characterized by adult onset, involuntary muscle jerks, cortical myoclonus and occasional seizures. FAME is genetically heterogeneous with more than 70 families reported worldwide and five potential disease loci. The efforts to identify potential causal variants have been unsuccessful in all but three families. To date, linkage analysis has been the main approach to find and narrow FAME critical regions. We propose an alternative method, pedigree free identity-by-descent (IBD) mapping, that infers regions of the genome between individuals that have been inherited from a common ancestor. IBD mapping provides an alternative to linkage analysis in the presence of allelic and locus heterogeneity by detecting clusters of individuals who share a common allele. Succeeding IBD mapping, gene prioritization based on gene co-expression analysis can be used to identify the most promising candidate genes. We performed an IBD analysis using high-density single nucleotide polymorphism (SNP) array data followed by gene prioritization on a FAME cohort of ten European families and one Australian/New Zealander family; eight of which had known disease loci. By identifying IBD regions common to multiple families, we were able to narrow the FAME2 locus to a 9.78 megabase interval within 2p11.2–q11.2. We provide additional evidence of a founder effect in four Italian families and allelic heterogeneity with at least four distinct founders responsible for FAME at the FAME2 locus. In addition, we suggest candidate disease genes using gene prioritization based on gene co-expression analysis.

Original languageEnglish
Pages (from-to)1-9
Number of pages9
JournalHuman Genetics
DOIs
Publication statusAccepted/In press - Jul 1 2016

Fingerprint

Myoclonic Epilepsy
Genes
Founder Effect
Gene Expression
Myoclonus
Chromosome Mapping
Pedigree
Single Nucleotide Polymorphism
Smooth Muscle
Seizures
Alleles
Genome

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Henden, L., Freytag, S., Afawi, Z., Baldassari, S., Berkovic, S. F., Bisulli, F., ... Bahlo, M. (Accepted/In press). Identity by descent fine mapping of familial adult myoclonus epilepsy (FAME) to 2p11.2–2q11.2. Human Genetics, 1-9. https://doi.org/10.1007/s00439-016-1700-8

Identity by descent fine mapping of familial adult myoclonus epilepsy (FAME) to 2p11.2–2q11.2. / Henden, Lyndal; Freytag, Saskia; Afawi, Zaid; Baldassari, S.; Berkovic, Samuel F.; Bisulli, Francesca; Canafoglia, Laura; Casari, Giorgio Nevio; Crompton, Douglas E.; Depienne, Christel; Gecz, Joseph; Guerrini, Renzo; Helbig, Ingo; Hirsch, E.; Keren, Boris; Klein, Karl Martin; Labauge, P.; Leguern, Eric; Licchetta, Laura; Mei, Davide; Nava, Caroline; Pippucci, T.; Rudolf, G.; Scheffer, Ingrid E.; Striano, Pasquale; Tinuper, Paolo; Zara, Federico; Corbett, Mark A.; Bahlo, Melanie.

In: Human Genetics, 01.07.2016, p. 1-9.

Research output: Contribution to journalArticle

Henden, L, Freytag, S, Afawi, Z, Baldassari, S, Berkovic, SF, Bisulli, F, Canafoglia, L, Casari, GN, Crompton, DE, Depienne, C, Gecz, J, Guerrini, R, Helbig, I, Hirsch, E, Keren, B, Klein, KM, Labauge, P, Leguern, E, Licchetta, L, Mei, D, Nava, C, Pippucci, T, Rudolf, G, Scheffer, IE, Striano, P, Tinuper, P, Zara, F, Corbett, MA & Bahlo, M 2016, 'Identity by descent fine mapping of familial adult myoclonus epilepsy (FAME) to 2p11.2–2q11.2', Human Genetics, pp. 1-9. https://doi.org/10.1007/s00439-016-1700-8
Henden, Lyndal ; Freytag, Saskia ; Afawi, Zaid ; Baldassari, S. ; Berkovic, Samuel F. ; Bisulli, Francesca ; Canafoglia, Laura ; Casari, Giorgio Nevio ; Crompton, Douglas E. ; Depienne, Christel ; Gecz, Joseph ; Guerrini, Renzo ; Helbig, Ingo ; Hirsch, E. ; Keren, Boris ; Klein, Karl Martin ; Labauge, P. ; Leguern, Eric ; Licchetta, Laura ; Mei, Davide ; Nava, Caroline ; Pippucci, T. ; Rudolf, G. ; Scheffer, Ingrid E. ; Striano, Pasquale ; Tinuper, Paolo ; Zara, Federico ; Corbett, Mark A. ; Bahlo, Melanie. / Identity by descent fine mapping of familial adult myoclonus epilepsy (FAME) to 2p11.2–2q11.2. In: Human Genetics. 2016 ; pp. 1-9.
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AU - Henden, Lyndal

AU - Freytag, Saskia

AU - Afawi, Zaid

AU - Baldassari, S.

AU - Berkovic, Samuel F.

AU - Bisulli, Francesca

AU - Canafoglia, Laura

AU - Casari, Giorgio Nevio

AU - Crompton, Douglas E.

AU - Depienne, Christel

AU - Gecz, Joseph

AU - Guerrini, Renzo

AU - Helbig, Ingo

AU - Hirsch, E.

AU - Keren, Boris

AU - Klein, Karl Martin

AU - Labauge, P.

AU - Leguern, Eric

AU - Licchetta, Laura

AU - Mei, Davide

AU - Nava, Caroline

AU - Pippucci, T.

AU - Rudolf, G.

AU - Scheffer, Ingrid E.

AU - Striano, Pasquale

AU - Tinuper, Paolo

AU - Zara, Federico

AU - Corbett, Mark A.

AU - Bahlo, Melanie

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