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Brief Communication
Nature Genetics  35, 125 - 127 (2003)
Published online: 7 September 2003; | doi:10.1038/ng1238

Mutations in NHLRC1 cause progressive myoclonus epilepsy

Elayne M Chan1, 2, Edwin J Young1, Leonarda Ianzano1, Iulia Munteanu1, Xiaochu Zhao1, Constantine C Christopoulos1, Giuliano Avanzini3, Maurizio Elia4, Cameron A Ackerley5, Nebojsa J Jovic6, Saeed Bohlega7, Eva Andermann8, Guy A Rouleau9, Antonio V Delgado-Escueta10, Berge A Minassian1, 11, 12 & Stephen W Scherer1, 2, 12

1  Program in Genetics and Genomic Biology, Research Institute, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada.

2  Department of Molecular and Medical Genetics, University of Toronto, Canada.

3  Instituto Nazionale Neurologico, Besta, Via Celoria, 11 20133 Milano, Italy.

4  Department of Neurology, Oasi Institute for Research on Mental Retardation and Brain Aging, Via Conte Ruggero, 73 94018 Troina, Italy.

5  Department of Pathology and Laboratory Medicine, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada.

6  Clinic of Neurology and Psychiatry for Children and Youth, Dr Subotica 6a St. 11 000 Belgrade, Serbia & Montenegro.

7  Department of Neurosciences, King Faisal Specialist Hospital & Research Centre, P.O. Box 3354 Riyadh 11211, Saudi Arabia.

8  Neurogenetics Unit, Montreal Neurological Institute, McGill University, 3801 University St. Montreal, Quebec H3A 2B4, Canada.

9  McGill University Health Centre Research Institute Centre for Research in Neuroscience, Montreal General Hospital, 1650 Cedar Ave. Montreal, Quebec H3G 1A4, Canada.

10  Comprehensive Epilepsy Program, Department of Neurology and Brain Research Institute, University of California, Los Angeles School of Medicine, West Los Angeles DVA Medical Center, 11301 Wilshire Blvd. Los Angeles, California 90073, USA.

11  Division of Neurology, Department of Pediatrics, The Hospital for Sick Children and University of Toronto, 555 University Ave., Toronto, Ontario M5G 1X8, Canada.

12  These authors contributed equally to this work.

Correspondence should be addressed to Berge A Minassian bminass@sickkids.ca or Stephen W Scherer steve@genet.sickkids.on.ca
Lafora progressive myoclonus epilepsy is characterized by pathognomonic endoplasmic reticulum (ER)-associated polyglucosan accumulations. We previously discovered that mutations in EPM2A cause Lafora disease. Here, we identify a second gene associated with this disease, NHLRC1 (also called EPM2B), which encodes malin, a putative E3 ubiquitin ligase with a RING finger domain and six NHL motifs. Laforin and malin colocalize to the ER, suggesting they operate in a related pathway protecting against polyglucosan accumulation and epilepsy.


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Nature Genetics
ISSN: 1061-4036
EISSN: 1546-1718
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