Affiliations: [a] Unit of Neuromuscular Diseases, Department of Neurology Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, ‘Sapienza’ University of Rome, Rome, Italy
Neuromuscular Morphology Unit, Myology Institute, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris, France
Department of Translational Medicine, IGBMC, U964, UMR7104, Strasbourg University, Illkirch, France
| [d] Unit of Neuromuscular and Neurodegenerative Disorders, Laboratory of Molecular Medicine, Bambino Gesú Children’s Research Hospital, Rome, Italy
| [e] Laboratory of Medical Genetics, Bambino Gesù Children’s Research Hospital, Rome, Italy
Department of Radiology, Istituto Dermopatico dell’Immacolata, IRCCS, Rome, Italy
Correspondence to: Matteo Garibaldi, MD, Unit of Neuromuscular Diseases, Department of Neurology Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, ‘Sapienza’ University of Rome, Sant’Andrea Hospital, Via di Grottarossa 1035-1039, 00189 Roma, Italy. Tel.: +39 06 33775937; Fax: +39 06 33775900; E-mail: email@example.com.
Abstract: We present the clinical, morphological and molecular data of an Italian family with centronuclear myopathy, carrying a novel pathogenic mutation of BIN1 gene in heterozygous state, consistent with autosomal dominant inheritance. The proband, a 56-years-old man suffered of lower limbs myalgia and slight CK elevation. Clinical examination revealed no muscle weakness, short stature, mild symmetric eyelid ptosis, scapular winging, ankle retraction and well-developed muscles. Muscle biopsy showed nuclear centralization and clustering, deep sarcolemmal invaginations and type 1 fibers hypotrophy. Muscle MRI revealed fatty infiltration of posterior legs compartments, lumbar paraspinal and serratus muscles. By sequencing BIN1, we identified a heterozygous pathogenic mutation [c.107C>A (p.A36E)], and we demonstrate that the mutation strongly impairs the membrane tubulation property of the protein. One affected sister with similar phenotype carried the same mutation. Our findings expand the clinical, morphological and genetic spectrum of the autosomal dominant CNM associated with BIN1 mutations.