• Norma B Romero, Ting Xie, Edoardo Malfatti, Ursula Schaeffer, Johann Böhm, Bin Wu, Fengping Xu, Samy Boucebci, Stéphane Mathis, Jean-Philippe Neau, Nicole Monnier, Michel Fardeau, and Jocelyn Laporte.
• Neuromuscular Morphology Unit, Myology Institute, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris, France Inserm, U974, Paris, France University Pierre et Marie Curie- Paris 6, UM 76, CNRS, UMR 7215, Myology Institute, IFR14, Paris, France Centre de référence de Pathologie Neuromusculaire Paris-Est, Institut de Myologie, GHU La Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France.
• J. Neurol. Neurosurg. Psychiatr.. 2014 Oct 1;85(10):1149-52.

BackgroundAutosomal dominant (AD) central core disease (CCD) is a congenital myopathy characterised by the presence of cores in the muscle fibres which correspond to broad areas of myofibrils disorganisation, Z-line streaming and lack of mitochondria. Heterozygous mutations in the RYR1 gene were observed in the large majority of AD-CCD families; however, this gene was excluded in some of AD-CCD families.ObjectiveTo enlarge the genetic spectrum of AD-CCD demonstrating mutations in an additional gene.Patients And MethodsFour affected AD family members over three generations, three of whom were alive and participate in the study: the mother and two of three siblings. The symptoms began during the early childhood with mild delayed motor development. Later they developed mainly tibialis anterior weakness, hypertrophy of calves and significant weakness (amyotrophic) of quadriceps. No cardiac or ocular involvement was noted.ResultsThe muscle biopsies sections showed a particular pattern: eccentric cores in type 1 fibres, associated with type 1 predominance. Most cores have abrupt borders. Electron microscopy confirmed the presence of both unstructured and structured cores. Exome sequencing analysis identified a novel heterozygous missense mutation p.Leu1723Pro in MYH7 segregating with the disease and affecting a conserved residue in the myosin tail domain.ConclusionsWe describe MYH7 as an additional causative gene for AD-CCD. These findings have important implications for diagnosis and future investigations of AD-congenital myopathies with cores, without cardiomyopathy, but presenting a particular involvement of distal and quadriceps muscles.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

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