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|Title:||Mutation of the Nuclear Lamin Gene LMNB2 in Progressive Myoclonus Epilepsy with Early Ataxia.|
|Authors:||Damiano, John Anthony;Afawi, Zaid;Bahlo, Melanie;Mauermann, Monika;Misk, Adel;Arsov, Todor;Oliver, Karen L;Dahl, Hans-Henrik M;Shearer, A Eliot;Smith, Richard J H;Hall, Nathan E;Mahmood, Khalid;Leventer, Richard J;Scheffer, Ingrid E;Muona, Mikko;Lehesjoki, Anna-Elina;Korczyn, Amos D;Hermann, Harald;Berkovic, Samuel F;Hildebrand, Michael S|
|Affiliation:||Bioinformatics Division, The Walter and Eliza Hall Institute, Melbourne, Australia.|
Division of Molecular Genetics, German Cancer Research Centre, Heidelberg, Germany.
Department of Neurology, Shaare Zedek Medical Center, Jerusalem, Israel.
Molecular Otolaryngology & Renal Research Laboratories, Department of Otolaryngology-Head and Neck Surgery, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA.
Life Sciences Computation Centre, VLSCI, Melbourne, Australia La Trobe Institute for Molecular Sciences, La Trobe University, Melbourne Australia.
Life Sciences Computation Centre, VLSCI, Melbourne, Australia.
Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Melbourne; Victoria, Australia Murdoch Children's Research Institute, Melbourne, Victoria, Australia Department of Neurology, Royal Children's Hospital, Melbourne, Victoria, Australia.
Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Melbourne, Victoria, Australia Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Melbourne; Victoria, Australia The Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Melbourne, Victoria, Australia.
Institute for Molecular Medicine, Neuroscience Centre, and Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland Folkhålsan Institute of Genetics, Helsinki, Finland.
Sackler School of Medicine, Tel Aviv University, Ramat-Aviv, 69978, Tel-Aviv, Israel.
Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Melbourne, Victoria, Australia.
|Citation:||Human Molecular Genetics 2015; 24(16): 4483-90|
|Abstract:||We studied a consanguineous Palestinian Arab family segregating an autosomal recessive progressive myoclonus epilepsy (PME) with early ataxia. PME is a rare, often fatal syndrome, initially responsive to antiepileptic drugs which over time becomes refractory, and can be associated with cognitive decline. Linkage analysis was performed and the disease locus narrowed to chromosome 19p13.3. Fourteen candidate genes were screened by conventional Sanger sequencing and in one, LMNB2, a novel homozygous missense mutation was identified that segregated with the PME in the family. Whole exome sequencing excluded other likely pathogenic coding variants in the linked interval. In vitro assembly analysis of mutant lamin B2 protein revealed a distinct defect in the assembly of the highly ordered fibrous arrays typically formed by wild-type lamin B2. Our data suggests that disruption of the organisation of the nuclear lamina in neurons, perhaps through abnormal neuronal migration, causes the epilepsy and early ataxia syndrome, and extends the etiology of PMEs to include dysfunction in nuclear lamin proteins.|
|Internal ID Number:||25954030|
|Appears in Collections:||Journal articles|
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