دورية أكاديمية
Biallelic MYORG mutation carriers exhibit primary brain calcification with a distinct phenotype
| العنوان: | Biallelic MYORG mutation carriers exhibit primary brain calcification with a distinct phenotype |
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| المؤلفون: | Grangeon, Lou, Wallon, David, Charbonnier, Camille, Quenez, Olivier, Richard, Anne-Claire, Rousseau, Stéphane, Budowski, Clara, Lebouvier, Thibaud, Corbillé, Anne-Gaëlle, Vidailhet, Marie, Méneret, Aurélie, Roze, Emmanuel, Anheim, Mathieu, Tranchant, Christine, Favrole, Pascal, Antoine, Jean-Christophe, Defebvre, Luc, Ayrignac, Xavier, Labauge, Pierre, Pariente, Jérémie, Clanet, Michel, Maltête, David, Rovelet-Lecrux, Anne, Boland, Anne, Deleuze, Jean-François, Frebourg, Thierry, Hannequin, Didier, Campion, Dominique, Nicolas, Gaël |
| المساهمون: | UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Normandie Université (NU), Département de neurologie Lille, Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille), Service de neurologie Nantes, Université de Nantes (UN)-Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes)-Hôpital Guillaume-et-René-Laennec Saint-Herblain, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière AP-HP, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie Aix-en-Provence, Centre Hospitalier du Pays d'Aix, Service de Neurologie CHU de Saint-Étienne, Centre Hospitalier Universitaire de Saint-Etienne CHU Saint-Etienne (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM), Département de neurologie Montpellier, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire Montpellier (CHRU Montpellier)-Hôpital Gui de Chauliac CHU Montpellier, Centre Hospitalier Régional Universitaire Montpellier (CHRU Montpellier)-Université de Montpellier (UM), Toulouse NeuroImaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Département Neurologie CHU Toulouse, Pôle Neurosciences CHU Toulouse, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Différenciation et communication neuronale et neuroendocrine (DC2N), Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Service de neurologie Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), ANR-17-CE14-0008,CALCIPHOS,ROLE DE L'EXPORTATEUR DE PHOSPHATE DANS LA CALCIFICATION VASCULAIRE(2017) |
| المصدر: | ISSN: 0006-8950. |
| بيانات النشر: | HAL CCSD Oxford University Press |
| سنة النشر: | 2019 |
| المجموعة: | Université Toulouse III - Paul Sabatier: HAL-UPS |
| مصطلحات موضوعية: | MESH: phenotype, computed tomography, mutation, genes, pons, brain, autosomal recessive inheritance, cerebellar atrophy, calcification, [SDV]Life Sciences [q-bio] |
| الوصف: | International audience ; Primary familial brain calcification (PFBC) is a rare neurogenetic disorder with diverse neuropsychiatric expression. Mutations in four genes cause autosomal dominant PFBC: SLC20A2, XPR1, PDGFB and PDGFRB. Recently, biallelic mutations in the MYORG gene have been reported to cause PFBC with an autosomal recessive pattern of inheritance. We screened MYORG in 29 unrelated probands negatively screened for the autosomal dominant PFBC genes and identified 11 families with a biallelic rare or novel predicted damaging variant. We studied the clinical and radiological features of 16 patients of these 11 families and compared them to that of 102 autosomal dominant PFBC patients carrying a mutation in one of the four known autosomal dominant PFBC genes. We found that MYORG patients exhibited a high clinical penetrance with a median age of onset of 52 years (range: 21–62) with motor impairment at the forefront. In particular, dysarthria was the presenting sign in 11/16 patients. In contrast to patients with autosomal dominant PFBC, 12/15 (80%) symptomatic patients eventually presented at least four of the following five symptoms: dysarthria, cerebellar syndrome, gait disorder of any origin, akinetic-hypertonic syndrome and pyramidal signs. In addition to the most severe clinical pattern, MYORG patients exhibited the most severe pattern of calcifications as compared to the patients from the four autosomal dominant PFBC gene categories. Strikingly, 12/15 presented with brainstem calcifications in addition to extensive calcifications in other brain areas (lenticular nuclei, thalamus, cerebellar hemispheres, vermis, ±cortex). Among them, eight patients exhibited pontine calcifications, which were observed in none of the autosomal dominant PFBC patients and hence appeared to be highly specific. Finally, all patients exhibited cerebellar atrophy with diverse degrees of severity on CT scans. We confirmed the existence of cerebellar atrophy by performing MRI voxel-based morphometry analyses of MYORG ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/31009047; hal-02538301; https://normandie-univ.hal.science/hal-02538301Test; PUBMED: 31009047 |
| DOI: | 10.1093/brain/awz095 |
| الإتاحة: | https://doi.org/10.1093/brain/awz095Test https://normandie-univ.hal.science/hal-02538301Test |
| رقم الانضمام: | edsbas.FCEE4E0 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/brain/awz095 |
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