P09.084C - Strong interest of exome sequencing in progressive neurological diseases

International audienceIntroduction: Neurogenetics represents a vast, complex, ever changing discipline whose diagnosis currently remains challenging, since clinical and/or imaging features frequently appear very unspecific, especially early in the evolution (cerebellar ataxia, tremor, dystonia...). In molecular diagnosis, current strategies usually include sequential investigations that may lead to long, tedious, expensive and disappointing patients care. Exome sequencing (ES) appears a promising approach for neurogenetics, apart from when nucleotide motif expansion disorders can be suspected. Materials and Methods: We recruited 48 individuals without cognitive development impairment, referred to our center for suspected neurogenetic disease: 20 cerebellar ataxia (42%), 12 neuromuscular diseases (25%), 8 spastic paraplegia (17%), 2 abnormal movements (4%) and 6 others (12%) for whom the phenotype could not be labelled under a usual neurological syndrome. ES was interpreted in a solo-based strategy (94%) or in trio with parental pool (6%). Results: ES identified a causal diagnosis in 4/8 individuals with spastic paraplegia (50%), 3/6 “other” (50%), 1/2 with abnormal movements (50%), 5/12 with neuromuscular diseases (42%), 4/11 with isolated cerebellar ataxia (37%) and 2/9 with spinocerebellar ataxia (22%). Overall diagnostic yield was of 40 %. Conclusions: With such overall diagnostic yield, this study reinforces the diagnostic interest of ES in neurogenetics, in all its fields, as this diagnostic yield ranges from 22% in spinocerebellar ataxia (which is higher than current yield of gene panels) to 50% in spastic paraplegia. It also includes situations in which clinical displays may be complex and hard to systematize. First-tier implementation would significantly improve diagnostic yield in neurogenetics

Self-report questionnaire vs. clinical evaluation form in the French National Registry on facioscapulohumeral dystrophy: a statistical comparison

5th Congress of the European-Academy-of-Neurology (EAN), Oslo, NORWAY, JUN 29-JUL 02, 2019International audienc

The DM-scope registry: a rare disease innovative framework bridging the gap between research and medical care

International audienceBackground: The relevance of registries as a key component for developing clinical research for rare diseases (RD) and improving patient care has been acknowledged by most stakeholders. As recent studies pointed to several limitations of RD registries our challenge was (1) to improve standardization and data comparability; (2) to facilitate interoperability between existing RD registries; (3) to limit the amount of incomplete data; (4) to improve data quality. This report describes the innovative concept of the DM-Scope Registry that was developed to achieve these objectives for Myotonic Dystrophy (DM), a prototypical example of highly heterogeneous RD. By the setting up of an integrated platform attractive for practitioners use, we aimed to promote DM epidemiology, clinical research and patients care management simultaneously.Results: The DM-Scope Registry is a result of the collaboration within the French excellence network established by the National plan for RDs. Inclusion criteria is all genetically confirmed DM individuals, independently of disease age of onset. The dataset includes social-demographic data, clinical features, genotype, and biomaterial data, and is adjustable for clinical trial data collection. To date, the registry has a nationwide coverage, composed of 55 neuromuscular centres, encompassing the whole disease clinical and genetic spectrum. This widely used platform gathers almost 3000 DM patients (DM1 n = 2828, DM2 n = 142), both children (n = 322) and adults (n = 2648), which accounts for > 20% of overall registered DM patients internationally. The registry supported 10 research studies of various type i.e. observational, basic science studies and patient recruitment for clinical trials.Conclusion: The DM-Scope registry represents the largest collection of standardized data for the DM population. Our concept improved collaboration among health care professionals by providing annual follow-up of quality longitudinal data collection. The combination of clinical features and biomolecular materials provides a comprehensive view of the disease in a given population. DM-Scope registry proves to be a powerful device for promoting both research and medical care that is suitable to other countries. In the context of emerging therapies, such integrated platform contributes to the standardisation of international DM research and for the design of multicentre clinical trials. Finally, this valuable model is applicable to other RDs

The DM-scope registry: a rare disease innovative framework bridging the gap between research and medical care

International audienceBackground: The relevance of registries as a key component for developing clinical research for rare diseases (RD) and improving patient care has been acknowledged by most stakeholders. As recent studies pointed to several limitations of RD registries our challenge was (1) to improve standardization and data comparability; (2) to facilitate interoperability between existing RD registries; (3) to limit the amount of incomplete data; (4) to improve data quality. This report describes the innovative concept of the DM-Scope Registry that was developed to achieve these objectives for Myotonic Dystrophy (DM), a prototypical example of highly heterogeneous RD. By the setting up of an integrated platform attractive for practitioners use, we aimed to promote DM epidemiology, clinical research and patients care management simultaneously.Results: The DM-Scope Registry is a result of the collaboration within the French excellence network established by the National plan for RDs. Inclusion criteria is all genetically confirmed DM individuals, independently of disease age of onset. The dataset includes social-demographic data, clinical features, genotype, and biomaterial data, and is adjustable for clinical trial data collection. To date, the registry has a nationwide coverage, composed of 55 neuromuscular centres, encompassing the whole disease clinical and genetic spectrum. This widely used platform gathers almost 3000 DM patients (DM1 n = 2828, DM2 n = 142), both children (n = 322) and adults (n = 2648), which accounts for > 20% of overall registered DM patients internationally. The registry supported 10 research studies of various type i.e. observational, basic science studies and patient recruitment for clinical trials.Conclusion: The DM-Scope registry represents the largest collection of standardized data for the DM population. Our concept improved collaboration among health care professionals by providing annual follow-up of quality longitudinal data collection. The combination of clinical features and biomolecular materials provides a comprehensive view of the disease in a given population. DM-Scope registry proves to be a powerful device for promoting both research and medical care that is suitable to other countries. In the context of emerging therapies, such integrated platform contributes to the standardisation of international DM research and for the design of multicentre clinical trials. Finally, this valuable model is applicable to other RDs