TY  - JOUR
AU  - Damiano, John A
AU  - Afawi, Zaid
AU  - Bahlo, Melanie
AU  - Mauermann, Monika
AU  - Misk, Adel
AU  - Arsov, Todor
AU  - Oliver, Karen L
AU  - Dahl, Hans-Henrik M
AU  - Shearer, A Eliot
AU  - Smith, Richard J H
AU  - Hall, Nathan E
AU  - Mahmood, Khalid
AU  - Leventer, Richard J
AU  - Scheffer, Ingrid E
AU  - Muona, Mikko
AU  - Lehesjoki, Anna-Elina
AU  - Korczyn, Amos D
AU  - Herrmann, Harald
AU  - Berkovic, Samuel F
AU  - Hildebrand, Michael S
TI  - Mutation of the nuclear lamin gene LMNB2 in progressive myoclonus epilepsy with early ataxia.
JO  - Human molecular genetics
VL  - 24
IS  - 16
SN  - 1460-2083
CY  - Oxford
PB  - Oxford Univ. Press
M1  - DKFZ-2017-02431
SP  - 4483 - 4490
PY  - 2015
AB  - 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 is located in an evolutionarily highly conserved region of the alpha-helical rod of the lamin B2 protein. 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 aetiology of PMEs to include dysfunction in nuclear lamin proteins.
KW  - Lamin Type B (NLM Chemicals)
KW  - lamin B2 (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:25954030
DO  - DOI:10.1093/hmg/ddv171
UR  - https://inrepo02.dkfz.de/record/126402
ER  -