Genotype-phenotype correlations in recessive titinopathies

Autor: Marco Savarese, Olivera Casar-Borota, Nuria Muelas, Claudio Bruno, Anna Sarkozy, Guja Astrea, Christoffer Ehrstedt, Marika Pane, Ricardo Rojas-García, Rita Barresi, Thierry Kuntzer, Jordi Díaz-Manera, Fortunato Lonardo, Bjarne Udd, Mridul Johari, Alessandro Malandrini, Juan J. Vílchez, Eugenio Mercuri, Francesco Muntoni, Sushan Luo, Giorgio Tasca, Ana Ferreiro, C. Julien, Mark M. Davis, Heidi Fodstad, Annalaura Torella, Salla Välipakka, Amets Sáenz, Vincenzo Nigro, Manu Jokela, Adolfo López de Munain, Emily C. Oates, Anna Vihola, Peter Hackman, Chiara Fiorillo, Isabel Illa, Filippo M. Santorelli, Talha Qureshi, H. Luque, Philippe Petiot, Chong Bo Zhao
Přispěvatelé: University of Helsinki, Folkhälsan Research Center, Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, Fimlab Laboratories [Tampere, Finland], School of Biotechnology and Biomolecular Sciences, University of New South Wales [Sydney] (UNSW), Translational and Clinical Research Institute, Newcastle University, IRCCS Istituto Giannina Gaslini [Genoa, Italy], Fondazione 'Policlinico Universitario A. Gemelli' [Rome], Tampere University Hospital, MRC Centre for Neuromuscular Diseases, University College of London [London] (UCL), Huashan Hospital [Shangai], CIBER de Enfermedades Raras (CIBERER), Uppsala University, Biodonostia Health Research Institute, Lausanne University Hospital, Service d'Explorations Fonctionnelles Respiratoires, Groupement Hospitalier Nord, Hôpital de la Croix-Rousse (Hospices Civiles de Lyon), Lyon, France, parent, Università degli studi della Campania 'Luigi Vanvitelli', IRCCS Fondazione Stella Maris [Pisa], Institut de Myologie, Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Sorbonne Université (SU), Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Università degli Studi di Siena = University of Siena (UNISI), Uppsala University Hospital, QEII Medical Centre, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università degli studi della Campania 'Luigi Vanvitelli' = University of the Study of Campania Luigi Vanvitelli, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Savarese, M., Vihola, A., Oates, E. C., Barresi, R., Fiorillo, C., Tasca, G., Jokela, M., Sarkozy, A., Luo, S., Diaz-Manera, J., Ehrstedt, C., Rojas-Garcia, R., Saenz, A., Muelas, N., Lonardo, F., Fodstad, H., Qureshi, T., Johari, M., Valipakka, S., Luque, H., Petiot, P., de Munain, A. L., Pane, M., Mercuri, E., Torella, A., Nigro, V., Astrea, G., Santorelli, F. M., Bruno, C., Kuntzer, T., Illa, I., Vilchez, J. J., Julien, C., Ferreiro, A., Malandrini, A., Zhao, C. -B., Casar-Borota, O., Davis, M., Muntoni, F., Hackman, P., Udd, B.
Jazyk: angličtina
Rok vydání: 2020
Předmět:
[SDV]Life Sciences [q-bio]
VARIANT
MYOPATHY
0302 clinical medicine
Genotype
congenital myopathy
Medicine
Missense mutation
Connectin
C-TERMINAL TITIN
Child
Genetics (clinical)
Genetics
0303 health sciences
arthrogryposi
Genetic disorder
High-Throughput Nucleotide Sequencing
musculoskeletal system
Hypotonia
3. Good health
Phenotype
Cohort
Muscle Hypotonia
medicine.symptom
Cohort study
EXPRESSION
TTN
Nonsense mutation
LINE
skeletal muscle disorders
SEQUENCE
arthrogryposis
03 medical and health sciences
skeletal muscle disorder
cardiomyopathy
titin
Humans
TRUNCATING MUTATIONS
Genetic Association Studies
030304 developmental biology
TIBIAL MUSCULAR-DYSTROPHY
business.industry
medicine.disease
Congenital myopathy
GENE
arthrogryposis
cardiomyopathy
congenital myopathy
skeletal muscle disorders
titin
Mutation
business
030217 neurology & neurosurgery
Zdroj: Genetics in Medicine
Genetics in Medicine, Nature Publishing Group, 2020, 22 (12), pp.2029-2040. ⟨10.1038/s41436-020-0914-2⟩
Genetics in Medicine, 2020, 22 (12), pp.2029-2040. ⟨10.1038/s41436-020-0914-2⟩
GENETICS IN MEDICINE
r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
instname
r-IIS La Fe. Repositorio Institucional de Producción Científica del Instituto de Investigación Sanitaria La Fe
r-IIB SANT PAU: Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
ISSN: 1098-3600
1530-0366
DOI: 10.1038/s41436-020-0914-2⟩
Popis: International audience; Purpose High throughput sequencing analysis has facilitated the rapid analysis of the entire titin (TTN) coding sequence. This has resulted in the identification of a growing number of recessive titinopathy patients. The aim of this study was to (1) characterize the causative genetic variants and clinical features of the largest cohort of recessive titinopathy patients reported to date and (2) to evaluate genotype-phenotype correlations in this cohort. Methods We analyzed clinical and genetic data in a cohort of patients with biallelic pathogenic or likely pathogenicTTNvariants. The cohort included both previously reported cases (100 patients from 81 unrelated families) and unreported cases (23 patients from 20 unrelated families). Results Overall, 132 causative variants were identified in cohort members. More than half of the cases had hypotonia at birth or muscle weakness and a delayed motor development within the first 12 months of life (congenital myopathy) with causative variants located along the entire gene. The remaining patients had a distal or proximal phenotype and a childhood or later (noncongenital) onset. All noncongenital cases had at least one pathogenic variant in one of the final threeTTNexons (362-364). Conclusion Our findings suggest a novel association between the location of nonsense variants and the clinical severity of the disease.
Databáze: OpenAIRE
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