title: Novel Dominant Mutation in BIN1 Gene Causing Mild Centronuclear Myopathy Revealed by Myalgias and CK Elevation.
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.
authors.affiliation: Unit of Neuromuscular Diseases, Department of Neurology Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, 'Sapienza' University of Rome, Rome, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Garibaldi
authors.affiliation: Department of Translational Medicine, IGBMC, U964, UMR7104, Strasbourg University, Illkirch, France.
authors.forename: Johann
authors.initials: J
authors.lastname: Böhm
authors.affiliation: Unit of Neuromuscular and Neurodegenerative Disorders, Laboratory of Molecular Medicine, Bambino Gesú Children's Research Hospital, Rome, Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Fattori
authors.affiliation: Department of Translational Medicine, IGBMC, U964, UMR7104, Strasbourg University, Illkirch, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Koch
authors.affiliation: Laboratory of Medical Genetics, Bambino Gesù Children's Research Hospital, Rome, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Surace
authors.affiliation: Department of Radiology, Istituto Dermopatico dell'Immacolata, IRCCS, Rome, Italy.
authors.forename: Pierfrancesco
authors.initials: P
authors.lastname: Ottaviani
authors.affiliation: Department of Radiology, Istituto Dermopatico dell'Immacolata, IRCCS, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Laschena
authors.affiliation: Department of Translational Medicine, IGBMC, U964, UMR7104, Strasbourg University, Illkirch, France.
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Laporte
authors.affiliation: Unit of Neuromuscular and Neurodegenerative Disorders, Laboratory of Molecular Medicine, Bambino Gesú Children's Research Hospital, Rome, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Bertini
authors.affiliation: Unit of Neuromuscular Diseases, Department of Neurology Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, 'Sapienza' University of Rome, Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Antonini
authors.affiliation: Neuromuscular Morphology Unit, Myology Institute, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris, France.
authors.forename: Norma B
authors.initials: NB
authors.lastname: Romero
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000368:Aged; D003402:Creatine Kinase / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D063806:Myalgia / Q000209:etiology / Q000503:physiopathology*; D020914:Myopathies, Structural, Congenital / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C101410:BIN1 protein, human; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; D003402:Creatine Kinase
keywords: CK elevation; Congenital myopathies; autosomal dominant BIN1 mutation; centronuclear myopathies (CNM); late-onset; myalgias