‘Dusty core disease’ (DuCD): expanding morphological spectrum of RYR1 recessive myopathies
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, immu...
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2019-01-01
|
| Series: | Acta Neuropathologica Communications |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s40478-018-0655-5 |
| _version_ | 1818510536477769728 |
|---|---|
| author | Matteo Garibaldi John Rendu Julie Brocard Emmanuelle Lacene Julien Fauré Guy Brochier Maud Beuvin Clemence Labasse Angeline Madelaine Edoardo Malfatti Jorge Alfredo Bevilacqua Fabiana Lubieniecki Soledad Monges Ana Lia Taratuto Jocelyn Laporte Isabelle Marty Giovanni Antonini Norma Beatriz Romero |
| author_facet | Matteo Garibaldi John Rendu Julie Brocard Emmanuelle Lacene Julien Fauré Guy Brochier Maud Beuvin Clemence Labasse Angeline Madelaine Edoardo Malfatti Jorge Alfredo Bevilacqua Fabiana Lubieniecki Soledad Monges Ana Lia Taratuto Jocelyn Laporte Isabelle Marty Giovanni Antonini Norma Beatriz Romero |
| author_sort | Matteo Garibaldi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T23:21:19Z |
| format | Article |
| id | doaj.art-c73f5437deee409b931e8b9a6c5226cb |
| institution | Directory Open Access Journal |
| issn | 2051-5960 |
| language | English |
| last_indexed | 2024-12-10T23:21:19Z |
| publishDate | 2019-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj.art-c73f5437deee409b931e8b9a6c5226cb2022-12-22T01:29:43ZengBMCActa Neuropathologica Communications2051-59602019-01-017111910.1186/s40478-018-0655-5‘Dusty core disease’ (DuCD): expanding morphological spectrum of RYR1 recessive myopathiesMatteo Garibaldi0John Rendu1Julie Brocard2Emmanuelle Lacene3Julien Fauré4Guy Brochier5Maud Beuvin6Clemence Labasse7Angeline Madelaine8Edoardo Malfatti9Jorge Alfredo Bevilacqua10Fabiana Lubieniecki11Soledad Monges12Ana Lia Taratuto13Jocelyn Laporte14Isabelle Marty15Giovanni Antonini16Norma Beatriz Romero17Neuromuscular Morphology Unit, Myology Institute, Groupe Hospitalier Universitaire La Pitié-SalpêtrièreCentre Hospitalier Universitaire de Grenoble Alpes, Biochimie Génétique et MoléculaireGrenoble Institut des Neurosciences- Inserm U1216 – UGANeuromuscular Morphology Unit, Myology Institute, Groupe Hospitalier Universitaire La Pitié-SalpêtrièreCentre Hospitalier Universitaire de Grenoble Alpes, Biochimie Génétique et MoléculaireNeuromuscular Morphology Unit, Myology Institute, Groupe Hospitalier Universitaire La Pitié-SalpêtrièreSorbonne 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-SalpêtrièreNeuromuscular Morphology Unit, Myology Institute, Groupe Hospitalier Universitaire La Pitié-SalpêtrièreNeuromuscular Morphology Unit, Myology Institute, Groupe Hospitalier Universitaire La Pitié-SalpêtrièreService Neurologie Médicale, Centre de Référence Maladies Neuromusculaire Paris-Est-Ile de France, CHU Raymond-Poincaré Paris OuestNeuromuscular Unit, Department of Neurology and Neurosurgery, University of Chile Clinical HospitalServicio de Neurología y Servicio de Patologia, Hospital de Pediatría GarrahanServicio de Neurología y Servicio de Patologia, Hospital de Pediatría GarrahanNeuropathology, Foundation for Neurological Research (FLENI)Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC)Grenoble Institut des Neurosciences- Inserm U1216 – UGAUnit of Neuromuscular Diseases, Neuromuscular Disease Centre, Department of Neurology Mental Health and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, SAPIENZA University of RomeNeuromuscular Morphology Unit, Myology Institute, Groupe Hospitalier Universitaire La Pitié-SalpêtrièreAbstract 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.http://link.springer.com/article/10.1186/s40478-018-0655-5RYR1 recessiveDusty Core DiseaseCentral Core DiseaseCongenital MyopathyCentronuclear myopathyRyanodine receptor |
| spellingShingle | Matteo Garibaldi John Rendu Julie Brocard Emmanuelle Lacene Julien Fauré Guy Brochier Maud Beuvin Clemence Labasse Angeline Madelaine Edoardo Malfatti Jorge Alfredo Bevilacqua Fabiana Lubieniecki Soledad Monges Ana Lia Taratuto Jocelyn Laporte Isabelle Marty Giovanni Antonini Norma Beatriz Romero ‘Dusty core disease’ (DuCD): expanding morphological spectrum of RYR1 recessive myopathies Acta Neuropathologica Communications RYR1 recessive Dusty Core Disease Central Core Disease Congenital Myopathy Centronuclear myopathy Ryanodine receptor |
| title | ‘Dusty core disease’ (DuCD): expanding morphological spectrum of RYR1 recessive myopathies |
| title_full | ‘Dusty core disease’ (DuCD): expanding morphological spectrum of RYR1 recessive myopathies |
| title_fullStr | ‘Dusty core disease’ (DuCD): expanding morphological spectrum of RYR1 recessive myopathies |
| title_full_unstemmed | ‘Dusty core disease’ (DuCD): expanding morphological spectrum of RYR1 recessive myopathies |
| title_short | ‘Dusty core disease’ (DuCD): expanding morphological spectrum of RYR1 recessive myopathies |
| title_sort | dusty core disease ducd expanding morphological spectrum of ryr1 recessive myopathies |
| topic | RYR1 recessive Dusty Core Disease Central Core Disease Congenital Myopathy Centronuclear myopathy Ryanodine receptor |
| url | http://link.springer.com/article/10.1186/s40478-018-0655-5 |
| work_keys_str_mv | AT matteogaribaldi dustycorediseaseducdexpandingmorphologicalspectrumofryr1recessivemyopathies AT johnrendu dustycorediseaseducdexpandingmorphologicalspectrumofryr1recessivemyopathies AT juliebrocard dustycorediseaseducdexpandingmorphologicalspectrumofryr1recessivemyopathies AT emmanuellelacene dustycorediseaseducdexpandingmorphologicalspectrumofryr1recessivemyopathies AT julienfaure dustycorediseaseducdexpandingmorphologicalspectrumofryr1recessivemyopathies AT guybrochier dustycorediseaseducdexpandingmorphologicalspectrumofryr1recessivemyopathies AT maudbeuvin dustycorediseaseducdexpandingmorphologicalspectrumofryr1recessivemyopathies AT clemencelabasse dustycorediseaseducdexpandingmorphologicalspectrumofryr1recessivemyopathies AT angelinemadelaine dustycorediseaseducdexpandingmorphologicalspectrumofryr1recessivemyopathies AT edoardomalfatti dustycorediseaseducdexpandingmorphologicalspectrumofryr1recessivemyopathies AT jorgealfredobevilacqua dustycorediseaseducdexpandingmorphologicalspectrumofryr1recessivemyopathies AT fabianalubieniecki dustycorediseaseducdexpandingmorphologicalspectrumofryr1recessivemyopathies AT soledadmonges dustycorediseaseducdexpandingmorphologicalspectrumofryr1recessivemyopathies AT analiataratuto dustycorediseaseducdexpandingmorphologicalspectrumofryr1recessivemyopathies AT jocelynlaporte dustycorediseaseducdexpandingmorphologicalspectrumofryr1recessivemyopathies AT isabellemarty dustycorediseaseducdexpandingmorphologicalspectrumofryr1recessivemyopathies AT giovanniantonini dustycorediseaseducdexpandingmorphologicalspectrumofryr1recessivemyopathies AT normabeatrizromero dustycorediseaseducdexpandingmorphologicalspectrumofryr1recessivemyopathies |