Journal article

Mutation of the nuclear lamin gene LMNB2 in progressive myoclonus epilepsy with early ataxia

John A Damiano, Zaid Afawi, Melanie Bahlo, Monika Mauermann, Adel Misk, Todor Arsov, Karen L Oliver, Hans-Henrik M Dahl, A Eliot Shearer, Richard JH Smith, Nathan E Hall, Khalid Mahmood, Richard J Leventer, Ingrid E Scheffer, Mikko Muona, Anna-Elina Lehesjoki, Amos D Korczyn, Harald Herrmann, Samuel F Berkovic, Michael S Hildebrand

HUMAN MOLECULAR GENETICS | OXFORD UNIV PRESS | Published : 2015

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. The p.His157Tyr mutation i..

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Grants

Awarded by National Health and Medical Research Council (NHMRC) Program Grant


Awarded by National Health and Medical Research Council (NHMRC) Australia Fellowship


Awarded by National Health and Medical Research Council (NHMRC) Practitioner Fellowship


Awarded by National Health and Medical Research Council (NHMRC) Career Development Fellowship


Awarded by Australian Research Council (ARC) Future Fellowship


Awarded by NHMRC Program Grant


Awarded by German Research Foundation


Awarded by NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES


Funding Acknowledgements

This work was supported by National Health and Medical Research Council (NHMRC) Program Grant (628952) to S.F.B. and I.E.S., an Australia Fellowship (466671) to S.F.B., a Practitioner Fellowship (1006110) to I.E.S and a Career Development Fellowship (1063799) to M.S.H. M.B. was supported by an Australian Research Council (ARC) Future Fellowship (FT100100764) and NHMRC Program Grant (APP1054618). This work was also supported by Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS funding. H.H. received funding from the German Research Foundation (DFG HE 1853/11-1, FOR 1228).