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Émilie Guettard, MD; Marie-France Portnoi, MD; Katja Lohmann-Hedrich, PhD; Boris Keren, MD; Sylvie Rossignol, MD; Susen Winkler, BS; Imen El Kamel, MD; Smaranda Leu, MD; Emmanuelle Apartis, MD, PhD; Marie Vidailhet, MD; Christine Klein, MD; Emmanuel Roze, MD, PhD

Arch Neurol. 2008;65(10):1380-1385.

Background  Myoclonus-dystonia is a movement disorder often associated with mutations in the maternally imprinted -sarcoglycan (SGCE) gene located on chromosome 7q21. Silver-Russell syndrome is a heterogeneous disorder characterized by prenatal and postnatal growth restriction and a characteristic facies, caused in some cases by maternal uniparental disomy of chromosome 7.

Objectives  To describe and investigate the combination of a typical myoclonus-dystonia syndrome and Silver-Russell syndrome.

Design  Clinical and neurophysiological examination as well as cytogenetic and molecular analyses.

Setting  Movement disorder clinic.

Patient  A 36-year-old man with typical myoclonus-dystonia and Silver-Russell syndrome.

Main Outcome Measures  Clinical description of the disease and its genetic cause.

Results  Cytogenetic analysis revealed mosaicism for a small chromosome 7 marker chromosome. Microsatellite analysis indicated loss of the paternal allele and maternal uniparental disomy of chromosome 7. In keeping with the maternal imprinting mechanism, no unmethylated allele of SGCE was detected after bisulfite treatment of the patient's DNA, and reverse transcription–polymerase chain reaction demonstrated loss of SGCE expression. Molecular analysis ruled out mutations in the SGCE gene.

Conclusions  We identified a new genetic alteration—maternal chromosome 7 disomy—that can cause myoclonus-dystonia. This alteration results in repression of both alleles of the maternally imprinted SGCE gene and suggests SGCE loss of function as the disease mechanism.

Author Affiliations: Service de Neurologie (Drs Guettard, Leu, Vidailhet, and Roze), Laboratoire de Cytogénétique (Drs Portnoi and El Kamel), and Service de Neurophysiologie (Dr Apartis), Hôpital Saint-Antoine, AP-HP, Paris, France; Department of Neurology, University of Lübeck, Lübeck, Germany (Drs Lohmann-Hedrich and Klein and Ms Winkler); Service de Génétique, Hôpital de la Salpêtrière, AP-HP, Paris (Dr Keren); Service d’explorations fonctionnelles endocriniennes, Hôpital Armand-Trousseau, AP-HP, and Institut national de la santé et de la recherche médicale U515, Université Pierre et Marie Curie-Paris VI, Paris (Dr Rossignol); and Centre National de la Recherche Scientifique, UMR 7102, Université Paris VI, Paris (Dr Roze). Drs Guettard, Leu, Vidailhet, and Roze are now with Pôle des maladies du système nerveux, Fédération de neurologie, Hôpital de la Salpêtrière, AP-HP, Paris.

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