2010•Unpublished venueRequires access
Phenotype genotype analysis in 15 patients presenting a congenital myasthenic syndrome due to mutations in DOK7 A. Ben AmmarF. PetitN. AlexandriK. GaudonS. Bauche ´ • A. RoucheD. Gras • E. FournierJ. KoenigT. StojkovicA. LacourP. PetiotF. ZagnoliL. Viollet • N. PellegriniD. OrlikowskiL. LazaroX. FerrerG. StoltenburgM. Paturneau-Jouas • F. HentatiM. FardeauD. SternbergD. Hantaõ ¨ • P. RichardB. Eymard
Abdelkerim Asma Ben, Ammar N. Alexandri, Gras J. Koenig, Marion Paturneau-Jouas, Daniel Hantaı̈, B. Eymard, Groupe Hospitalier Pitié, François Petit, Nektaria Alexandri, Tanya Stojkovic, Damien Sternberg, Pascale Richard, Emmanuel Fournier, Groupe Hospitalier, Jeanine Koenig, A. Lacour, Chu de Lille, P. Petiot, Fabien Zagnoli, Louis Viollet, Nadine Pellegrini, David Orlikowski, L. Lazaro, Xavier Ferrer, Stoltenburg M. Fardeau
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Abstract
Congenital myasthenic syndromes (CMSs) are a heterogeneous group of diseases caused by genetic defects affecting neuromuscular transmission. Mutations of DOK7 have recently been described in recessive forms of CMS. Dok-7 is a cytoplasmic post-synaptic protein co- activator of the muscle-specific receptor-tyrosine kinase (MuSK) involved in neuromuscular synaptogenesis and maintenance. We report clinical, morphological and molecular data on 15 patients with mutations in DOK7. Eleven different mutations (5 novel) were identified and all patients but one were found to carry at least the common c.1124_1127dupTGCC mutation. Patients with DOK7 mutations have a particular limb-girdle pattern, without tubular aggregates but a frequent lipidosis on the muscle biopsy. Changes in pre- and post-synaptic compartments of the neuromuscular junction were also observed in muscle