title: Atypical nuclear abnormalities in a patient with Brody disease.
abstract: Brody disease was first described as a benign pseudo-myotonic disorder with muscular stiffness, which increased with exercise. Biochemical and genetic studies have pointed out its close relationship to a functional defect of the fast-twitch sarcoplasmic reticulum Ca(++) ATPase pump (SERCA1) encoded by the ATP2A1 gene located on chromosome 16. The histopathological features in this form of myopathy were generally described as non-specific, i.e. moderate degree of type 2 fibre atrophy and excess of internal nuclei. We here present the clinical and histopathological features of a patient with Brody disease over a 19-year follow-up period. This patient had two heterozygous ATP2A1 mutations and complained about muscle stiffness immediately after effort. He had suffered from this since early childhood and exhibited clinical symptoms mimicking myotonia. Histological, ultrastructural and cytogenetic analyses revealed morphologically abnormal nuclei with polyploidy. In this report, we discuss the possible links between the consequences of the genetic abnormality and the peculiar aspect of the nuclei.
authors.affiliation: Laboratoire d'Anatomie Pathologique, CHU de Nantes, Nantes, France; Centre de Référence Maladies Neuromusculaires Nantes-Angers, CHU de Nantes, Nantes, France.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Mussini
authors.affiliation: Centre de Référence Maladies Neuromusculaires Nantes-Angers, CHU de Nantes, Nantes, France; Atlantic Gene Therapies - Biotherapy Institute for Rare Diseases, Nantes, France.
authors.forename: Armelle
authors.initials: A
authors.lastname: Magot
authors.affiliation: Institut de Myologie, Hôpital de La Salpêtrière, Paris, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hantaï
authors.affiliation: Institut de Myologie, Hôpital de La Salpêtrière, Paris, France; Laboratoire de Biochimie, Hôpital de La Salpêtrière, Paris, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Sternberg
authors.affiliation: Institut de Myologie, Hôpital de La Salpêtrière, Paris, France; Neuropathologisches Institut, Universitätsklinikum Erlangen, 91054 Erlangen, Germany.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Chevessier
authors.affiliation: Centre de Référence Maladies Neuromusculaires Nantes-Angers, CHU de Nantes, Nantes, France; Atlantic Gene Therapies - Biotherapy Institute for Rare Diseases, Nantes, France. Electronic address: Yann.Pereon@univ-nantes.fr.
authors.forename: Yann
authors.initials: Y
authors.lastname: Péréon
mesh_terms: D000328:Adult; D002467:Cell Nucleus / Q000473:pathology*; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D009129:Muscle Tonus; D018482:Muscle, Skeletal / Q000648:ultrastructure*; D009154:Mutation; D009224:Myotonia Congenita / Q000235:genetics / Q000473:pathology*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics
chemical_list: D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506943:ATP2A1 protein, human
keywords: Brody disease; Myopathology; Polyploid muscle cells; SERCA1