Epsilon sarcoglycan mutations and phenotype in French patients with myoclonic syndromes

Sophie Tezenas du Montcel ^1*, Fabienne Clot ², Marie Vidailhet ³, Emmanuel Roze ³, Philippe Damier ⁴, Charles Pierre Jedynak ¹, Agnès Camuzat ², Alain Lagueny ⁵, Laurent Vercueil ⁶, Diane Doummar ⁷, Lucie Guyant-Marechal ⁸, Jean-Luc Houeto ⁹, Gerard Ponsot ¹⁰, Stéphane Thobois ¹¹, Marie-Anne Cournelle ¹², Alexandra Durr ¹, Franck Durif ¹³, Bernard Echenne ¹⁴, Didier Hannequin ⁸, Christine Tranchant ¹⁵ and Alexis Brice ¹

¹ Groupe Hospitalier Pitie-Salpetriere, France
² INSERM U679, France
³ Hopital Saint Antoine, France
⁴ Hôpital Laennec, France
⁵ Hôpital du Haut-L'Evêque, France
⁶ CHU de Grenoble, France
⁷ Hôpital Armand Trousseau, France
⁸ Hôpital Charles Nicolle, France
⁹ Hôpital La Milétrie, France
¹⁰ Hôpital Saint Vincent de Paul, France
¹¹ Hôpital Pierre Wertheimer, France
¹² Centre Hospitalier du Pays d'Aix, France
¹³ Hôpital Gabriel Montpied, France
¹⁴ Hôpital Gui de Chauliac, France
¹⁵ Hôpital Civil de Strasbourg, France

^* To whom correspondence should be addressed. E-mail: sophie.tezenas{at}psl.aphp.fr.

Accepted 7 October 2005

Abstract

Background: Myoclonus Dystonia Syndrome (MDS) is an autosomal-dominant movement disorder caused by mutations in the epsilon-sarcoglycan gene (SGCE) on chromosome 7q21.

Methods: We have screened for SGCE mutations in index cases from 76 French patients with myoclonic syndromes, including myoclonus dystonia (M-D), essential myoclonus (E-M), primary myoclonic dystonia, generalized dystonia, dystonia with tremor and benign hereditary chorea. All coding exons of the SGCE gene were analyzed. The DYT1 mutation was also tested.

Results: Sixteen index cases had SGCE mutations whereas one with primary myoclonic dystonia carried the DYT1 mutation. Thirteen different mutations were found: 5 nonsense, 3 missense, 3 splice site mutations, 4 deletions and 1 insertion. Eleven of the SGCE index cases had M-D and 5 E-M. No SGCE mutations were detected in patients with other phenotypes. The total number of mutation carriers in the families was 38, 6 of whom were asymptomatic. Penetrance was complete in paternal transmissions and null in maternal transmissions. MDS patients with SGCE mutation had a significantly earlier onset than the non-carriers. None of the patients had severe psychiatric disorders.

Conclusion: This large cohort of index patients shows that SGCE mutations are primarily found in patients with M-D and to a lesser extent E-M, but are present in only 30% of these patients combined (M-D and E-M).

Keywords: Myoclonus Dystonia, epsilon sarcoglycan gene, essential myoclonus, mutation, phenotype

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