Please use this identifier to cite or link to this item:
Title: Identity by descent fine mapping of familial adult myoclonus epilepsy (FAME) to 2p11.2-2q11.2
Austin Authors: Henden, Lyndal;Freytag, Saskia;Afawi, Zaid;Baldassari, Sara;Berkovic, Samuel F ;Bisulli, Francesca;Canafoglia, Laura;Casari, Giorgio;Crompton, Douglas E;Depienne, Christel;Gecz, Jozef;Guerrini, Renzo;Helbig, Ingo;Hirsch, Edouard;Keren, Boris;Klein, Karl Martin;Labauge, Pierre;LeGuern, Eric;Licchetta, Laura;Mei, Davide;Nava, Caroline;Pippucci, Tommaso;Rudolf, Gabrielle;Scheffer, Ingrid E ;Striano, Pasquale;Tinuper, Paolo;Zara, Federico;Corbett, Mark A;Bahlo, Melanie
Affiliation: Austin Health, Heidelberg, Victoria, Australia
Department of Medical Biology, the University of Melbourne, Parkville, Victoria, Australia
Tel Aviv University Medical School, Tel Aviv, Israel
Medical Genetics Unit, Polyclinic Sant'Orsola-Malpighi-Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
Epilepsy Research Centre, Department of Medicine, the University of Melbourne, Austin Health, Heidelberg, Victoria, Australia
IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy
Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy
Neurophysiopathology and Epilepsy Center, IRCCS Foundation C. Besta Neurological Institute, Milan, Italy
Division of Genetics and Cell Biology, Università Vita-Salute San Raffaele, San Raffaele Scientific Institute, Milan, Italy
Neurology Department, Northern Health, Epping, Victoria, Australia
Département de Médicine translationnelle et Neurogénétique, IGBMC, CNRS UMR 7104/INSERM U964/Université de Strasbourg, Illkirch, France
Laboratoire de diagnostic génétique, Hôpitaux Universitaires de Strasbourg, Strasbourg, France
Robinson Institute and School of Medicine, The University of Adelaide, Adelaide, South Australia, Australia
School of Biological Sciences, The University of Adelaide, Adelaide, South Australia, Australia
Pediatric Neurology, Neurogenetics and Neurobiology Unit and Laboratories, Neuroscience Department, A Meyer Children's Hospital, University of Florence, Florence, Italy
IRCCS Stella Maris Foundation, Pisa, Italy
Department of Neuropediatrics, Christian-Albrechts-University of Kiel and University Medical Center, Kiel, Schleswig-Holstein, Germany
Departments of Brain and Cognitive Sciences, Physiology and Cell Biology, Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Negev, Israel
Division of Neurology, The Children's Hospital of Philadelphia, Philadephia, PA, USA
Medical and Surgical Epilepsy Unit, Hautepierre Hospital, University of Strasbourg, Strasbourg, France
Département de Génétique, Hôpital de la Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France
Sorbonne Universités, UPMC Univ Paris 06,UMR S 1127, ICM, Paris, France
Department of Neurology, Epilepsy Center Frankfurt Rhine-Main, Center of Neurology and Neurosurgery, University Hospital, Goethe-University Frankfurt, Frankfurt, Germany
Department of Neurology, Epilepsy Center Hessen, University Hospitals Giessen and Marburg, Philipps-University Marburg, Marburg, Germany
Department of Neurology, Montpellier University, Gui de Chauliac, 34295, Montpellier, Cedex 5, France
INSERM, U 1127; CNRS, UMR 7225; INSERM UMR 975; Institut du Cerveau et de la Moelle Epinière; and Département de Génétique et de Cytogénétique, Hôpital de la Pitié-Salpêtrière, Assistance Publique-Hôpitaux De Paris (AP-HP), Paris, France
Université Pierre et Marie Curie (Paris 6) (UPMC), UMRS 975, Paris, France
Department of Neurology, Hautepierre Hospital, University of Strasbourg, Strasbourg, France
Florey Institute of Neuroscience and Mental Health, Heidelberg, Victoria, Australia
Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Parkville, Victoria, Australia
Pediatric Neurology and Muscular Diseases Unit, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Gaslini Institute, Genoa, Italy
Laboratory of Neurogenetics, Department of Neurosciences, Gaslini Institute, Genoa, Italy
Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
Issue Date: 1-Jul-2016
Date: 2016-07-01
Publication information: Human Genetics 2016; online first: 1 July
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.
DOI: 10.1007/s00439-016-1700-8
ORCID: 0000-0002-1121-9513
Journal: Human Genetics
PubMed URL:
Type: Journal Article
Appears in Collections:Journal articles

Show full item record

Page view(s)

checked on Jul 16, 2024

Google ScholarTM


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.