Open Access Open Badges Research article

Novel SCARB2 mutation in action myoclonus-renal failure syndrome and evaluation of SCARB2 mutations in isolated AMRF features

Franziska Hopfner12*, Barbara Schormair1, Franziska Knauf1, Achim Berthele163, Thomas R Tölle163, Ralf Baron164, Christoph Maier165, Rolf-Detlef Treede166, Andreas Binder164, Claudia Sommer167, Christian Maihöfner168, Wolfram Kunz9, Friedrich Zimprich10, Uwe Heemann11, Arne Pfeufer12, Michael Näbauer12, Stefan Kääb12, Barbara Nowak13, Christian Gieger14, Peter Lichtner12, Claudia Trenkwalder15, Konrad Oexle2 and Juliane Winkelmann123*

Author Affiliations

1 Institute of Human Genetics, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany

2 Institute of Human Genetics, Klinikum rechts der Isar, Technische Universität München, Munich, Germany

3 Department of Neurology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany

4 Sektion Neurologische Schmerzforschung und -therapie, Department of Neurology, Christian-Albrechts-Universität zu Kiel, Kiel, Germany

5 BG University Hospital Bergmannsheil Bochum, Bochum, Germany

6 Lehrstuhl für Neurophysiology, Medizinische Fakultät Mannheim der Ruprecht-Karls-Universität Heidelberg, Mannheim, Germany

7 Department of Neurology, Universitätsklinikum Würzburg, Würzburg, Germany

8 Department of Neurology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

9 Department of Epileptology and Life & Brain Center, Universität Bonn, Bonn, Germany

10 Department of Clinical Neurology, Medical University of Vienna, Vienna, Austria

11 Department of Nephrology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany

12 Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians-Universität München, Munich, Germany

13 Zentrum für Nieren- und Hochdruckkrankheiten, Immenstadt and Oberstdorf, Germany

14 Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany

15 Paracelsus-Elena-Klinik, Center of Parkinsonism and Movement Disorders, Kassel, Germany

16 Member of the German Research Network on Neuropathic Pain (DFNS

For all author emails, please log on.

BMC Neurology 2011, 11:134  doi:10.1186/1471-2377-11-134

Published: 27 October 2011



Action myoclonus-renal failure syndrome is a hereditary form of progressive myoclonus epilepsy associated with renal failure. It is considered to be an autosomal-recessive disease related to loss-of-function mutations in SCARB2. We studied a German AMRF family, additionally showing signs of demyelinating polyneuropathy and dilated cardiomyopathy.

To test the hypothesis whether isolated appearance of individual AMRF syndrome features could be related to heterozygote SCARB2 mutations, we screened for SCARB2 mutations in unrelated patients showing isolated AMRF features.


In the AMRF family all exons of SCARB2 were analyzed by Sanger sequencing. The mutation screening of unrelated patients with isolated AMRF features affected by either epilepsy (n = 103, progressive myoclonus epilepsy or generalized epilepsy), demyelinating polyneuropathy (n = 103), renal failure (n = 192) or dilated cardiomyopathy (n = 85) was performed as high resolution melting curve analysis of the SCARB2 exons.


A novel homozygous 1 bp deletion (c.111delC) in SCARB2 was found by sequencing three affected homozygous siblings of the affected family. A heterozygous sister showed generalized seizures and reduction of nerve conduction velocity in her legs. No mutations were found in the epilepsy, renal failure or dilated cardiomyopathy samples. In the polyneuropathy sample two individuals with demyelinating disease were found to be carriers of a SCARB2 frameshift mutation (c.666delCCTTA).


Our findings indicate that demyelinating polyneuropathy and dilated cardiomyopathy are part of the action myoclonus-renal failure syndrome. Moreover, they raise the possibility that in rare cases heterozygous SCARB2 mutations may be associated with PNP features.