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Acta Neuropathol Commun. 2019 Jan 5;7(1):3. doi: 10.1186/s40478-018-0655-5.

'Dusty core disease' (DuCD): expanding morphological spectrum of RYR1 recessive myopathies.

Author information

1
Neuromuscular Morphology Unit, Myology Institute, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris, France. matteo.garibaldi@uniroma1.it.
2
Unit of Neuromuscular Diseases, Neuromuscular Disease Centre, 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, Rome, Italy. matteo.garibaldi@uniroma1.it.
3
Centre Hospitalier Universitaire de Grenoble Alpes, Biochimie Génétique et Moléculaire, Grenoble, France.
4
Grenoble Institut des Neurosciences- Inserm U1216 - UGA, Grenoble, France.
5
Neuromuscular Morphology Unit, Myology Institute, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris, France.
6
Sorbonne Universités UPMC Univ Paris 06- Inserm UMRS974, Center of Research in Myology, Institut de Myologie, Centre de Référence Maladies Neuromusculaire Paris-Est-Ile de France, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
7
Service Neurologie Médicale, Centre de Référence Maladies Neuromusculaire Paris-Est-Ile de France, CHU Raymond-Poincaré Paris Ouest, Garches, France.
8
U1179 UVSQ-INSERM Handicap Neuromusculaire: Physiologie, Biothérapie et Pharmacologie appliquées, UFR des sciences de la santé Simone Veil, Université Versailles-Saint-Quentin-en-Yvelines, Versailles, France.
9
Neuromuscular Unit, Department of Neurology and Neurosurgery, University of Chile Clinical Hospital, Santiago, Chile.
10
Department of Anatomy and Legal Medicine, Faculty of Medicine, University of Chile, Santiago, Chile.
11
Servicio de Neurología y Servicio de Patologia, Hospital de Pediatría Garrahan, Buenos Aires, Argentina.
12
Neuropathology, Foundation for Neurological Research (FLENI), Buenos Aires, Argentina.
13
Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), 1, rue Laurent Fries, BP 10142, 67404, Illkirch, France.
14
INSERM U1258, 67404, Illkirch, France.
15
CNRS, UMR7104, 67404, Illkirch, France.
16
Université de Strasbourg, 67404, Illkirch, France.
17
Unit of Neuromuscular Diseases, Neuromuscular Disease Centre, 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, Rome, Italy.

Abstract

Several morphological phenotypes have been associated to RYR1-recessive myopathies. We recharacterized the RYR1-recessive morphological spectrum by a large monocentric study performed on 54 muscle biopsies from a large cohort of 48 genetically confirmed patients, using histoenzymology, immunohistochemistry, and ultrastructural studies. We also analysed the level of RyR1 expression in patients' muscle biopsies. We defined "dusty cores" the irregular areas of myofibrillar disorganisation characterised by a reddish-purple granular material deposition with uneven oxidative stain and devoid of ATPase activity, which represent the characteristic lesion in muscle biopsy in 54% of patients. We named Dusty Core Disease (DuCD) the corresponding entity of congenital myopathy. Dusty cores had peculiar histological and ultrastructural characteristics compared to the other core diseases. DuCD muscle biopsies also showed nuclear centralization and type1 fibre predominance. Dusty cores were not observed in other core myopathies and centronuclear myopathies. The other morphological groups in our cohort of patients were: Central Core (CCD: 21%), Core-Rod (C&R:15%) and Type1 predominance "plus" (T1P+:10%). DuCD group was associated to an earlier disease onset, a more severe clinical phenotype and a lowest level of RyR1 expression in muscle, compared to the other groups. Variants located in the bridge solenoid and the pore domains were more frequent in DuCD patients. In conclusion, DuCD is the most frequent histopathological presentation of RYR1-recessive myopathies. Dusty cores represent the unifying morphological lesion among the DuCD pathology spectrum and are the morphological hallmark for the recessive form of disease.

KEYWORDS:

Central Core Disease; Centronuclear myopathy; Congenital Myopathy; Dusty Core Disease; RYR1 recessive; Ryanodine receptor

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